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Differential effect of honey on selected variables in alloxan-induced and fructose- induced diabetic rats


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Honey contains a high concentration of fructose, a monosaccharide, capable of raising blood sugar level after oral ingestion. It is thus a paradox that nutritional experts have advocated its use as a nutrition supplement in patients with diabetes mellitus. It has also been used, over the years, as a sweetener by those who wish to avoid the use of sugar. The effective use of sugar in diabetes may be due to its other constituents, especially the various antioxidants that are abundant in honey. Glycemic effect of honey on alloxaninduced diabetes and with concomitant administration of fructose was studied in male rats of the Wistar strain. Alloxan was injected into the rats through a tail artery and three days later, a confirmation of successful induction of diabetes was made by demonstration of hyperglycemia in the rats. Another group of rats received daily oral ingestion of fructose. At the end of three weeks it was found that daily ingestion of honey for three weeks progressively and effectively reduced blood glucose level in rats with alloxaninduced diabetes. Honey also caused a reduction in hyperglycemia induced by long-term ingestion of fructose, albeit to a lesser degree than its effect on alloxan-induced hyperglycemia. Honey could not reduce blood glucose in controlled rats that received neither alloxan treatment nor fructose ingestion, even though it caused an increase in body weight, irrespective of other substances concomitantly administered to the rats. It is thus apparent that honey may be a useful adjunct in the management of diabetes, while serving as a sweetener, especially if taken in moderate quantities. (Afr. J. Biomed. Res. 11: 191 - 196) Key Words: Honey, Alloxan-induced diabetes, Fructose-induced diabetes, Rats
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African Journal of Biomedical Research, Vol. 11 (2008); 191-196
ISSN 1119 – 5096 © Ibadan Biomedical Communications Group
Abstracted by:
African Index Medicus (WHO), CAB Abstracts, Index Copernicus, Global Health Abstracts, Asian Science Index, Index
Veterinarius, Bioline International , African Journals online
Full-text available at
August, 2007
Accepted (Revised):
March 2008
May 2008
Full Length Research Article
Differential Effect of Honey on Selected
Variables in Alloxan-Induced and Fructose-
Induced Diabetic Rats
*Adesoji A Fasanmade and Oluwakemi T Alabi
Departments of Physiology and Medicine
College of Medicine, University of Ibadan
Ibadan, Nigeria
Honey contains a high concentration of fructose, a monosaccharide, capable
of raising blood sugar level after oral ingestion. It is thus a paradox that
nutritional experts have advocated its use as a nutrition supplement in patients
with diabetes mellitus. It has also been used, over the years, as a sweetener by
those who wish to avoid the use of sugar. The effective use of sugar in
diabetes may be due to its other constituents, especially the various
antioxidants that are abundant in honey. Glycemic effect of honey on alloxan-
induced diabetes and with concomitant administration of fructose was studied
in male rats of the Wistar strain. Alloxan was injected into the rats through a
tail artery and three days later, a confirmation of successful induction of
diabetes was made by demonstration of hyperglycemia in the rats. Another
group of rats received daily oral ingestion of fructose. At the end of three
weeks it was found that daily ingestion of honey for three weeks
progressively and effectively reduced blood glucose level in rats with alloxan-
induced diabetes. Honey also caused a reduction in hyperglycemia induced by
long-term ingestion of fructose, albeit to a lesser degree than its effect on
alloxan-induced hyperglycemia. Honey could not reduce blood glucose in
controlled rats that received neither alloxan treatment nor fructose ingestion,
even though it caused an increase in body weight, irrespective of other
substances concomitantly administered to the rats. It is thus apparent that
honey may be a useful adjunct in the management of diabetes, while serving
as a sweetener, especially if taken in moderate quantities.
(Afr. J. Biomed. Res. 11: 191 - 196)
Key Words: Honey, Alloxan-induced diabetes, Fructose-induced diabetes, Rats
*Corresponding Author: E-mail:
African Journal of Biomedical Research 2008 (Vol. 11) / Fasanmade and Alabi
Glycemic effect of honey on alloxan-induced diabetes
The non-communicable chronic diseases prevalent
in the developing countries of Tropical Africa
include sickle cell disease, hypertension and
diabetes mellitus. There is an increasing advocacy
of alternate therapy in the management of these
and other diseases, as the use of Western
medicines are costly and at best are useful only for
control of these diseases. Several alternate
therapies include honey as an important
component in the management of diabetes but the
mechanism for its hypoglycaemic effect has not
been clearly understood. Elevation of plasma
insulin levels and lowering of blood glucose levels
have been observed in patients with diabetes after
administration of honey (Al-Waili N, 2003; Al-
Waili NS, 2004). Other studies have also
demonstrated that honey may be important in
reduction of some biochemical markers that are
linked to an increased risk of heart disease
(Shambaugh et al 1990). Hyperlipidaemia and
insulin resistance have also been shown to be
better after consumption of honey (Katsilambros et
al 1988).
Ingestion of high doses of fructose over a
prolonged period has been used to induce
persistent hyperglycaemia rats with features
similar to those seen in patients with type 2
diabetes mellitus (DM), hence its use in type 2-
like DM induction in animals (Ostos et al 2002).
Natural honey contains a high concentration of
fructose and so it is puzzling that honey would
lower blood glucose levels in humans with DM.
This study was thus designed to study the
glycaemic effects of honey on alloxan-induced
DM (akin to type 1 DM), and fructose-induced
DM (akin to type 2 DM) in male Wistar rats. It is
assumed that honey would not reduce the level of
hyperglycaemia induced by fructose, even if it
does in the rats with alloxan-induced DM.
Attempts will be made to explain the differential
effects thus elucidated.
48 matured male Wistar rats, each weighing about
200g, were used for the study. They were allowed
2-week acclimatization to laboratory environment
and were divided randomly into six groups of
eight rats as follows:
Group 1a served as control rats. They were
given standard rat chow for three weeks.
Group 1b rats were given honey along with
standard rat chow for three weeks.
Group 2a rats were administered alloxan
according to standard procedure (Szkudelski et
al, 1998) on day 1 of the study and those that
developed diabetes after three days were
thereafter given standard rat chow for three
Group 2b rats were treated as those of group 2a
but were given honey along with standard rat
chow after diabetes induction with alloxan.
Group 3a rats were given standard rat chow and
fructose for three weeks.
Group 3b rats were given standard rat chow
fructose for three weeks. Thereafter honey was
given along with standard rat chow and
fructose for a further period of three weeks.
In effect, corresponding subgroup a served as
control for subgroup b and group 1a also served as
overall control for all the groups.
D-Fructose (BDH, Poole, England) with a
molecular weight of 180.16 was used for the
study. Each rat, regardless of weight, consumed a
solution containing 6.6g of fructose/5ml of
distilled water (through an oral cannula) daily.
The standard rat chow given was obtained from
a commercial outlet in Ibadan, Nigeria as pellets,
which contain 67.9% of starch, 21.0% of protein,
3.5% of fat, 6.0% of fiber, 0.8% of minerals and
0.8% of vitamins. Each rat consumed 3.4g of the
pellets per day.
Fructose (67.9%) was substituted for starch in
the rats that were given fructose (Comte etal,
2004; Grover etal, 2005).
Honey was obtained from, and certified pure by
the Wildlife Unit of the Department of Forestry,
University of Ibadan. Each rat on honey received a
daily dose of 10ml honey/kg/5ml of distilled water
(Busserolles etal, 2002) through an oral cannula.
Alloxan (Sigma Aldrich, St Quentin-Fallavier,
France) with a pH of 7.0 was kept at 370C before
injection through a vein of the penis at a dose of
65mg alloxan/kg (Gruppuso etal 1990; Boylan et
African Journal of Biomedical Research 2008 (Vol. 11) / Fasanmade and Alabi
Glycemic effect of honey on alloxan-induced diabetes 193
al 1992) after a 24-hr fast. Prior, light anaesthesia
was induced in the rats (with 0.6ml of
25%w/v/100g of rat) before intravenous
administration of alloxan. Blood sugar was
evaluated 72hr later to confirm effective induction
of DM (as hperglycaemia).
The rats were weighed weekly from the start of
the study (i.e. at the end of the two weeks of
acclimatization to the laboratory environment),
with a laboratory scale (Harvard Trip Balance,
Florham Park, NJ, USA) to the nearest gram.
Blood was collected from the tail of the rats by
nipping with a pair of fine scissors. Blood sugar
was estimated from a drop of blood so collected
with a glucometer (PRESTIGE SMART
SYSTEMTM, Home Diagnostics, Inc, Ft
Lauderdale, USA). Glucose estimation was made
weekly throughout the period of the study.
The measured glucose values and the weights
of the rats were subjected to statistical analysis,
using the SPSS v 11 statistical package and
Microsoft Excel 2007. Data were expressed as
mean ± SEM. Values were compared using
student – t test and differences in the values were
considered statistically significant when P<0.05.
Six of the rats in group 3a died before the end of
the experiment and supplemental rats were
provided and similarly treated until there were
eight that stayed alive until the end of the study.
Two rats died in group 2a but the rats in the other
groups survived the period of the study.
Rats in groups 1a, 1b, 3a and 3b progressively
gained weight, whereas those of groups 2a and 2b,
i. e. the ones that had alloxan-induced diabetes had
progressive weight loss after an initial slight
weight increase. However, the alloxan-induced
diabetic rats that were given honey had less weight
loss. The weight changes of the rats are shown in
Table 1.
Changes in the blood glucose levels in the rats are
shown in Figure 1. There was a steady rise in the
blood glucose level in all animal groups during the
course of the study. In group 1a, the blood glucose
rise was not significant. Addition of honey as
supplement to the diet (group 1b) led to a steady
significant rise in blood glucose. At the end of the
third week, blood glucose had risen to double the
value at the start of the study.
Table 1:
Changes in body weight (in grams) of the rats
Treatment Group Body weight at
basal level Body weight at end
of wk 1 Body weight at end
of wk 2 Body weight at end
of wk 3
1a – Control: on rat chow 197.04 ± 10.17 196.75 ± 22.91 220.87 ± 28.68 251.25 ± 36.02*
1b – Rat chow + honey 204.63 ± 12.94 243.87 ± 33.59# 285.37 ± 38.94*# 307.50 ± 40.69*#
2a – Alloxan treated + rat
chow 219.72 ± 7.30 220.12 ± 9.04 215.62 ± 12.08 185.00 ± 14.51*
2b – Alloxan + rat chow +
honey 211.62 ± 14.08 229.75 ± 20.78 220.12 ± 17.59 198.75 ± 15.97*
3a – Fructose + rat chow 207.11 ± 8.71 181.25 ± 8.75 198.37 ± 11.76 200.00 ± 13.49*
3b – Fructose + rat chow +
honey 201.14 ± 9.32 213.75 ± 5.64# 237.37 ± 4.64*# 240.00 ± 11.95*#
All values are mean ± S.E.M, n (no of rats per group) = 8
* = statistically different from basal level (p<0.05)
# = statistically different from corresponding values in subgroup a (p<0.05)
African Journal of Biomedical Research 2008 (Vol. 11) / Fasanmade and Alabi
Glycemic effect of honey on alloxan-induced diabetes
Figure 1.
Changes in blood glucose levels in the rats (1a – Control: on rat chow; 1b – Rat chow + honey; 2a – Alloxan treated
+ rat chow; 2b – Alloxan + rat chow + honey; 3a – Fructose + rat chow; 3b – Fructose + rat chow + honey
The rise in blood glucose in group 2a rats was
about 10 times the basal value. There was a slight
drop at the end of week 2 and a further drop at the
end of week 3, but the difference in values of the
blood glucose at the end of each week was highly
significant (p < 0.01). Addition of honey as a
supplement to the diet of rats treated with alloxan
(group 2b) caused a significant drop in blood
glucose level. This fall was also steady from the
start to the end of the study. The difference in
corresponding blood glucose levels between
groups 2a and 2b was significant (p<0.05).
The rats that received fructose as part of their diet
(group 3a) had a slight but steady rise in blood
glucose levels, such that at the end of the third
week, the blood glucose level had risen to double
the basal value. Honey supplementation in the rats
receiving fructose (group 3b) resulted in slight
reduction in blood glucose levels. The reduction
was, however, not statistically significant
Pancreatic β cell destruction with alloxan has been
successfully used in the induction of type 1-like
diabetes mellitus in laboratory animals
(Szkudelski et al 1998). Induction of type 2-like
diabetes has been more difficult. Most of type 2
diabetes models [e.g. Kyoto (York 2004);
Koletsky (Takaya et al 1996); Ob/ob (York and
Hansen 1997) Tubby Mouse (Coleman and Eicher
1990; Zucker (Harris et al 1987)] have been
genetically derived. The method of (Comte et al
2004) used in this study is acceptable in that there
was a significant hyperglycemia following chronic
ingestion of fructose. It is not known, however, if
the hyperglycemia so induced is a reflection of
type 2-like diabetes.
Keeping the rats in the laboratory for a period
of three weeks resulted in progressive increase in
weight and blood glucose level, irrespective of
treatment given to them. It could be that the
regular consumption of the rat chow and aging
Basal wk1wk2wk3
African Journal of Biomedical Research 2008 (Vol. 11) / Fasanmade and Alabi
Glycemic effect of honey on alloxan-induced diabetes 195
process are important factors to consider in this
It is apparent, however, that addition of honey,
as a supplement to the diet results in further
increase in weight in all the rats, irrespective of
treatment, and a reduction in blood glucose level
in the rats subjected to hyperglycemic maneuvers.
Honey is widely used in medical practice,
principally as a topical antibacterial agent and for
effective healing of ulcers, irrespective of the
cause of the ulcer (Dumronglert 1983). In treating
diarrhea, honey promotes the rehydration of the
body and more quickly clears up the diarrhea and
any vomiting and stomach upsets. The anti-
bacterial properties of honey, both the peroxide
and non-peroxide, are effective against several
strains of bacteria which are notoriously resistant
to antibiotics (Heggers 1987). Other topical uses
of honey include treatment and healing of eczema
and masking of acne (Green 1988). Health benefits
of honey use include anti-allergic properties.
Honey is also a sweetener, and in certain situations
it has replaced sugar. This is especially so in
patients with diabetes mellitus.
The distinct qualities of honey as a useful
agent in medical practice may be due to its unique
components. Honey is composed of minerals like
magnesium, potassium, calcium, sodium chlorine,
sulphur, copper, iodine, zinc, iron and phosphate.
It also contains vitamins B1, B2, C, B6, B5 and
B3, all of which change according to the qualities
of the nectar and pollen. The anti-oxidant effects
of honey (Gheldof et al 2002) would thus make it
a useful adjunct in the management of diabetes
The mechanism for the hypoglycemic effect of
honey is, however, not well understood. Honey is
a mixture of sugars – fructose (about 38.5%) and
glucose (about 31.0%), maltose, sucrose and other
complex carbohydrates. One would thus expect
that consumption of honey would raise the blood
sugar and that in fact the glycemic index of honey
should approach that of glucose. The finding in
several studies that honey causes a reduction in
blood glucose levels in both normal and diabetic
patients is an indication that honey has a
mechanism, probably insulin sensitization effect.
This has been suggested by Al – Waili (2004).
These studies were carried out over a period of
few hours in contrast to the present study which
spanned a period of three weeks. The failure of
honey to reduce blood glucose to appreciable
levels in the control rats (group 1a) despite a great
reduction in rats made hyperglycemic in this study
further buttresses the fact that the hypoglycemic
effect of honey may be as a result of multi-
factorial mechanisms, including insulin
sensitization and anti-oxidant activity. Otherwise
similar effect should have been observed in the
rats that were given fructose, a major constituent
of honey, along with the standard rat chow,
especially as fructose administration caused a
significant weight gain in the rats, similar to the
effect of honey on weight of the rats.
The results of animal experimentation may not
be truly extrapolated to human situation, but the
result of this study provides further evidence that
honey consumption, at least in moderate
quantities, may be a useful adjunct in the
management of diabetes mellitus.
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Fructose. The American Society for Nutritional
Sciences. J. Nutr. 132: 3379 – 3382
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... The available medications alone failed to control diabetes effectively, unable to prevent pancreatic beta cell destruction, having complications related to oxidative stress and other adverse effects including weight gain [25]. Honey has shown hypoglycemic effect on streptozotocin (STZ) and alloxan induced type 1 and 2 diabetic models [26,27]. The reduction in lipid content of serum in diabetic model along with hypoglycemic effect adds the effectiveness of honey [28]. ...
... In present study Ziziphus honey and its isolated protein by both oral and I.P routes significantly reduced fasting blood glucose level compared to non-treated diabetic rats ( Table 2). Previously the effect of honey on glycemic control was reported in alloxan and fructose induced diabetic rats [27]. The antidiabetic effect of honey in noise induced hyperglycemic rats and isolated proteins in streptozotocin inducedwas also reported [25,45]. ...
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Background Diabetes Mellitus (DM) poses a serious health problem worldwide and several inflammatory mediators are involved in the pathogenesis of this disease. Honey composed of various constituents which have been proven to have immunomodulatory and anti-inflammatory properties. The aim of this study is to investigate the in vitro and in vivo effects of Ziziphus honey and its isolated crude proteins in modulation of immune system and inflammation involved in the pathogenesis of diabetes. Methodology The proteins from Ziziphus honey were isolated by ammonium sulfate precipitation and estimated by Bradford method. In vitro anti-inflammatory activities were evaluated by inhibition of reactive oxygen species (ROS) from phagocytes via chemiluminescence immunoassay and nitric oxide (NO) by Griess method. Cytotoxicity was evaluated by MTT Assay. The comparative effect of oral and IP routes of honey and isolated proteins was observed in streptozotocin (STZ) induced diabetic male Wistar rats. qRT-PCR technique was utilized for gene expression studies. Results The honey proteins suppressed phagocyte oxidative burst and nitric oxide (NO) at significantly lower concentrations as compared to crude honey. The isolated proteins showed promising anti-inflammatory and hypoglycemic effects along with maintenance of body weight of rodents via both oral and IP routes, with significant down-regulation of inflammatory markers TNF-α, IL-1β, IFN-γ, iNOS, caspase 1, Calgranulin A (S100A8) and NF-κB expression in diabetic rats. Conclusion The isolated honey proteins showed better immunomodulatory and therapeutic potential at significantly lower doses as compared to crude honey.
... Besides several health benefits and the nutritional value ascribed to natural honey (Ajibola, Chamunorwa, & Erlwanger, 2012), various honey samples from different regions have been reported to exert beneficial effects with regards to diabetes and other related conditions in experimental and clinical studies. Honey's impact with respect to pre-clinical (Adesoji & Oluwakemi, 2008;Chepulis,&;Akhtar & Khan, 1989;Al-Waili, 2003a, 2003bAnyakudo, Balogun, & Adeniyi, 2015;Busserolles, Gueux, Rock, Mazur, & Rayssiguier, 2002;Chepulis, 2007;Erejuwa et al., 2016;Nasrolahi, Heidari, Rahmani, & Farokhi, 2012;Nemoseck et al., 2011;Omotayo et al., 2010;Starkey, 2008) and clinical (Abdulrhman, 2013;Abdulrhman, 2016;Abdulrhman, El-Hefnawy, Hussein, & El-Goud, 2011;Abdulrhman et al., 2013;Agrawal et al., 2007;Ahmad, Azim, Mesaik, Nazimuddin, & Khan, 2008;Al-Waili, 2003a, 2003bAl-Waili, 2004;Bahrami et al., 2009;Enginyurt et al., 2017;Gheldof, Wang, & Engeseth, 2003;Khalil, Shahjahan, & Absar, 2006;Larson-Meyer et al., 2010;Majid et al., 2013;Münstedt, Böhme, Hauenschild, & Hrgovic, 2011;Münstedt et al., 2008;Münstedt et al., 2009;Mushtaq, Mushtaq, & Khan, 2011;Rana, Sharma, Katare, Shrivatava, & Prasad, 2012;Samanta, Burden, & Jones, 1985;Shambaugh, Worthington, & Herbert, 1990) work can be realized from studies presented in Tables 1 and 2. ...
... They also confirmed that the therapeutic benefits of honey on metabolic derangements (glucose and lipid-related) tended to be lost or reduced at the high doses of honey (Erejuwa et al., , 2016. Another study on Nigerian honey in alloxan and fructose induced diabetic rats found that the daily intake of honey for three weeks improves hyperglycaemia and thus could be effectively used in diabetes management (Adesoji & Oluwakemi, 2008). Shorter duration of honey supplementation for one week in alloxan-induced diabetic rats showed mild antihyperglycemic effect (Bilkisu, Tukur, Sheriff, Sera, & Falmata, 2011). ...
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Background Honey is being used in Complementary and Alternative Medicine, especially in Indian Ayurvedic Medicine, as an adjuvant and supplement in diabetes mellitus treatment since immemorial times. In recent times, the use of honey has experienced a renewed interest in the context of diabetes treatment because of the rise in the accessibility of evidence-based pharmacological and clinical findings, signifying its health benefits. Scope and approach There are differential opinions regarding the traditional use of honey in diabetes mellitus. The present review highlights various research propositions, hoisted issues, and misconceptions regarding the effects of honey in diabetes management and presents current challenges and future perspectives. A comprehensive critical review was performed by probing the traditional antidiabetic claims of honey, considering published reports in online databases. Key findings and conclusions A total of 20 pre-clinical and 25 clinical studies investigated the antidiabetic effect of honey. Though in vivo studies are still limited, the findings reinforce the multi-targeted antidiabetic effect of honey, exerting antioxidant, nutritional, antihyperglycemic, immunomodulatory, anti-inflammatory, wound-healing, antihypertensive, hypolipidemic, and hypoglycaemic activities. Preclinical and clinical evidence suggests that honey may possess multi-faceted and adjunct effects to accomplish a better glycaemic control, ameliorate several metabolic derangements, and mitigate oxidative stress-evoked diabetic problems. Nevertheless, the findings remain inconclusive due to poor study designs and other limitations (e.g. short duration, few participants, the difference in type of study participants, varied honey sources, and administered doses). Overall, there is a significant gap in knowledge, and hence, carefully planned, detailed in vitro, in vivo, and clinical studies are warranted to reach better conclusions.
... The rats' body weights were reduced after induction of diabetes (Table 2). This kind of weight reduction was observed in alloxan-induced diabetes in rodents [52]. The breakdown of lipids stored in adipose tissues and the disruption of the skeletal muscle proteins might have contributed to this weight loss [53]. ...
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Aim: Onion is one of the commonly cultivated and consumed vegetables rich in nutrients and phytochemicals. Various nutraceuticals are found in the outer fleshy layers and dry peel of onion which usually is treated as a common biowaste. Diabetes mellitus is a leading non communicable disease causing hyperglycemia and increased production of free radicals that potentially disrupts antioxidant enzymatic activity. Considering global consumption of wheat, the present study was designed to evaluate the anti-hyperglycemic and antioxidant effects of wheat bread supplemented with onion peel extract (OPE) or onion powder (OP) on diabetic rats. Methods: In this study, ethanolic extract of onion peel and onion bulb were prepared separately. Male Sprague Dawley rats were divided into 6 groups ( n = 7). Different regimens of supplemented wheat bread (OPE (1% and 3%) and OP (5% and 7%)) were given to diabetic rats for eight weeks, plain bread was used as the control. Blood glucose level, body weight and activities of SOD, CAT, GPx, GR, GSH and MDA in the liver and kidney tissues were evaluated. Statistical analysis was performed using SPSS Version (25) and Dunnett’s multiple comparison test. Results: Bread supplemented with 1% and 3% onion peel extract and 7% onion powder significantly reduced blood glucose levels and MDA in the treated rats compared with the control group diabetic rats. Body weight of diabetic rats was reduced for control group, while onion supplemented diet improved the body weight of treated rats. Onion supplementation also brought significant improvement in antioxidant enzyme activities among the treated diabetic rats. Conclusion: These findings suggested that onion supplementation is effective in lowering blood glucose and could potentially aid in protecting organs from oxidative stress.
... In another study, honey and fructose were fed to type 1 diabetic (alloxan-induced) and healthy rats. The former showed a significant reduction in glucose levels, when compared to the latter in control rats [107,108]. It was also shown that honey effectively brought about glucose homeostasis when given in the diet for diabetics (or hypertriglyceridemia) and in healthy patients in contrast to a diet that is rich in sucrose and dextrose. ...
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Despite the availability of various antidiabetic drugs, diabetes mellitus (DM) remains one of the world's most prevalent chronic diseases and is a global burden. Hyperglycaemia, a characteristic of type 2 diabetes mellitus (T2DM), substantially leads to the generation of reactive oxygen species (ROS), triggering oxidative stress as well as numerous cellular and molecular modifications such as mitochondrial dysfunction affecting normal physiological functions in the body. In mitochondrial-mediated processes, oxidative pathways play an important role, although the responsible molecular mechanisms remain unclear. The impaired mitochondrial function is evidenced by insulin insensitivity in various cell types. In addition, the roles of master antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response elements (ARE) are being deciphered to explain various molecular pathways involved in diabetes. Dietary factors are known to influence diabetes, and many natural dietary factors have been studied to improve diabetes. Honey is primarily rich in carbohydrates and is also abundant in flavonoids and phenolic acids; thus, it is a promising therapeutic antioxidant for various disorders. Various research has indicated that honey has strong wound-healing properties and has antibacterial, anti-inflammatory, antifungal, and antiviral effects; thus, it is a promising antidiabetic agent. The potential antidiabetic mechanisms of honey were proposed based on its major constituents. This review focuses on the various prospects of using honey as an antidiabetic agent and the potential insights. © 2020 Visweswara Rao Pasupuleti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
... Fructose is the main carbohydrate in most types of honey (Fasanmade and Alabi, 2008). Carbohydrates with a low GI will trigger a slight increase in blood sugar level, as compared to those carbohydrates with a high GI. ...
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Diabetes mellitus (DM) is a metabolic disease characterised by chronic hyperglycaemia with impaired carbohydrate, fat and protein metabolism caused by defects in insulin secretion or action. Based on our previous research, stingless bee honey (SLBH) from Tetragonula biroi and T. laeviceps can inhibit alpha-glucosidase activities. Therefore, the aim of the present study was to determine the effects of daily oral administration of SLBH on body weight (BW) and fasting blood glucose (FBG) levels of male rats with streptozotocin (STZ)-induced DM. Thirty-six male Sprague Dawley rats were divided into six groups of six rats each. One group of normal non-diabetic rats served as a positive control. The diabetic groups were intraperitoneally (i.p.) injected with STZ (50 mg/kg BW) for induction of DM and divided into five equal subgroups of six animals each: an untreated group as a negative control; a group treated with 0.6 mg/kg BW of glibenclamide as a positive control and three SLBN treatment groups that had daily oral administration of 0.5, 1.0 or 2.0 g/kg BW, respectively, for 35 days. The results showed that SLBH significantly reduced loss of BW in diabetic rats. FBG levels in diabetic rat blood, collected from the tail, were measured using Accu-Chek test strips. The FBG levels in diabetic rats that have oral administered intake with glibenclamide and SLBH were stable. There were no changes in serum FBG levels in SLBH-treated diabetic rats for 35 days. Pancreatic histopathology results from all groups showed no abnormalities or tissue damage in either diabetic or non-diabetic rats. The results of this study show that administration of SLBH reduced BW loss or improved BW of rats with STZ-induced DM. Meanwhile, the reduction in loss of BW that occurred in diabetic rats after 35 days of SLBH administration was the result of reduced formation of fats and proteins, which are broken down into energy. Further research is needed to determine the antidiabetic effects of honey from other stingless honeybee species.
... It is therefore a paradox that researchers and nutritionists have encouraged the use of honey as a nutrition supplement in diabetic individuals. [2,88] All these studies documented the therapeutic benefit of honey in various diseases, including obesity and diabetes. Therefore, it is essential that honey should match international quality standard. ...
This chapter emphasizes the profile and characteristics of bee products relevant to diabetes mellitus (DM) and their use in DM management. The chapter summarizes and analyses recent scientific data from both preclinical and clinical trials indicating the bee products’ potential in treating DM. Bee products have hypoglycemic, antihyperglycemic, antihyperlipidemic, antioxidant, and antiinflammatory properties, which are favorable factors for diabetics and their control. Bee products reduce oxidative stress, advanced glycation end products (AGE) build-up and adipose tissue inflammation, all of which contribute to insulin resistance and secretion abnormalities, which ameliorate diabetic complications, including nephropathy, retinopathy foot ulcers and nonalcoholic fatty liver disease.
Wu-tou decoction has been used as a traditional Chinese medicine prescription for thousands of years. It is composed of five herbs, namely, Radix Aconiti Preparata, Ephedrae Herba, Astragali Radix, Glycyrrhiza Radix and Paeoniae Radix Alba. In addition, the original prescription also contains honey, but in modern research, the existence of honey is commonly ignored. To investigate the effect of absorption in rats after oral wu-tou decoction within or without honey. In this research, a rapid and sensitive UPLC-MS/MS method was investigated to the quantitative analysis of ephedrine, pseudoephedrine, paeoniflorin, calycosin-7-glucoside, glycyrrhizic acid, liquiritin and benzoylmesaconine in rat plasma after single and continuous oral decoctions. The results of pharmacokinetic parameters showed that Cmax , CL/F, AUC0-t and AUC0-∞ in the honey group were significantly increased than those in the non-honey group except for ephedrine, pseudoephedrine. It obtained the same trend regardless of single or continuous oral administration. The research showed that honey could promote the absorption of some effective components in wutou decoction in rats, enhance bioavailability, and provide a theoretical basis for the scientific and rational compatibility of the original prescription.
IntroductionThe effect of the natural sources of fructose such as high fructose fruits and honey on the risk of fatty liver is still challenging. This study aimed to compare the effect of fructose, high fructose fruits, and honey on the metabolic factors and non-alcoholic fatty liver disease (NAFLD).Methods Forty-four rats were divided into four groups including normal diet group, high fructose group (HF), high fructose fruits group (HFF), and honey group (HO). After 120 days of intervention, the levels of insulin resistance, hepatic enzyme, and lipid profile were measured. Also, the expression levels of the acetyl-coA carboxylase (ACC), sterol regulatory element-binding protein 1c (SREBP-1c), Interleukin 6 (IL-6), and transforming growth factor-beta (TGF-β) genes were assessed. In addition, a histopathologic assessment was performed on liver tissues.ResultsInsulin resistance (IR) increased significantly in the HF, HFF, and HO groups (All P < 0.05). The levels of liver enzymes was significantly increased only in the group receiving the HF regimen (P < 0.01). A significant decrease in total cholesterol and HDL-C (high density lipoprotein cholesterol) levels was found in HO group compared to the control group (P < 0.05). The expression levels of ACC and SREBP-1c genes in HF, HFF, and HO groups were significantly higher than the control group (All P < 0.05). The HF group had a greater increase in the level of gene expression of IL-6 and TGF-β (All P < 0.05). Histopathological assessment did not find any changes in fatty liver formation and inflammatory damage.Conclusion Consumption of fructose-rich honey and fruits improved the status of inflammatory markers and liver enzymes compared with the industrial fructose-rich products.
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Polypeptide hormone signal transmission by receptor tyrosine kinases requires the rapid reversal of tyrosine phosphorylation by protein phosphotyrosine phosphatases (PPTPases). We studied hepatic PPTPases in the rat with emphasis on acute and chronic regulation by insulin. PPTPase activity with artificial substrates ([32P]Tyr-reduced, carboxyamidomethylated, and maleylated lysozyme and [32P]Tyr-poly[glutamic acid:tyrosine] 4:1) was present in distinct membrane, cytoskeletal, and cytosolic fractions. These PPTPase activities were unaffected by alloxan diabetes. Acute administration of insulin to normal animals also did not change PPTPase activity in liver plasma membranes or endosomal membranes. Although alloxan diabetes did not affect PPTPase activity measured with artificial substrates or with epidermal growth factor receptors, a decrease in insulin receptor dephosphorylation was noted. Dephosphorylation of hepatic receptors from normal and diabetic rats by membrane PPTPase from control rats was similar. These results indicate that alloxan diabetes does not lead to a generalized effect on hepatic PPTPase activity, although a substrate-specific decrease in activity with the insulin receptor may occur.
Animal models have played an important role in advancing our understanding of the causes and consequences of obesity. The spontaneous single gene mutations led to the discovery of leptin and the melanocortin signaling pathways and were important to the understanding of hypothalamic systems that control energy balance. The use of transgenic and gene targeting technologies has opened a new era of investigation, identifying new genes that regulate the development or prevention of obesity and providing the tools for proof of function of genes. These studies have shown that a wide range of genes expressed primarily in the central nervous system or in adipose tissue are potential targets for the treatment of obesity.
The Minimal Inhibitory Concentration (MIC) and the Nathan's Agar Well Diffusion (NAWD) tests are bacterial antimicrobial susceptibility predictors. Some suggest that the NAWD is not as reliable as the MIC test. We compared the MIC and NAWD tests as to how well they agree to bacterial sensitivity or resistance and predicted clinical outcome of burn wound infections. Using 65 bacterial isolates from burned patients, the MIC and NAWD tests agreed in 60.0% of the isolates (vs. a perfect agreement of 100%, p less than 0.001), implying that these tests are not interchangeable. From 18 burned patients treated with nitrofurazone or mafenide acetate, 28 infectious isolates were evaluated. The outcome of these infections was correctly predicted by NAWD in 92.8% and the MIC in 72.0% of the cases (p less than 0.05). It seems that for burns treated with topical antimicrobials, the NAWD is a more reliable predictor of bacterial susceptibility.
This report describes the development of obesity syndromes in mice caused by two autosomal recessive mutations, fat (fat), located on chromosome 8, and tubby (tub), located on chromosome 7. Both mutations cause slowly developing but ultimately severe obesity conditions. Although hyperinsulinemia, hyperactivity of the beta cell of the islets of Langerhans, and beta-cell degranulation are consistent features, these obesity syndromes do not progress to severe diabetes. The many different single-gene mutations in the mouse that produce obesity-diabetes syndromes of varying degrees of severity make the mutant mouse a powerful tool for analyzing the number and nature of the primary defects than can cause obesity states.
It is now recognized that dietary carbohydrate components influence the prevalence and severity of common degenerative diseases such as dental problems, diabetes, heart disease and obesity. Fructose and sucrose have been evaluated and compared to glucose using glucose tolerance tests, but few such comparisons have been performed for a "natural" sugar source such as honey. In this study, 33 upper trimester chiropractic students volunteered for oral glucose tolerance testing comparing sucrose, fructose and honey during successive weeks. A 75-gm carbohydrate load in 250 ml of water was ingested and blood sugar readings were taken at 0, 30, 60, 90, 120 and 240 minutes. Fructose showed minimal changes in blood sugar levels, consistent with other studies. Sucrose gave higher blood sugar readings than honey at every measurement, producing significantly (p less than .05) greater glucose intolerance. Honey provided the fewest subjective symptoms of discomfort. Given that honey has a gentler effect on blood sugar levels on a per gram basis, and tastes sweeter than sucrose so that fewer grams would be consumed, it would seem prudent to recommend honey over sucrose.
The metabolic effects of honey - alone or combined with other foods - were investigated in type II diabetics using 2 protocols: A) 33 g honey and 50 g bread (same amounts of carbohydrate) were given on alternate days to 12 patients. Blood levels of glucose, insulin and triglycerides were determined in venous samples before and every 30 min after meal ingestion (for a total of 3h). Areas under glucose curves were equal, although honey - compared to bread - resulted in higher blood sugar concentrations at 30 min (p less than 0.01) and lower at 90 min (p less than 0.05). B) Another 19 type II diabetics consumed on separate days 3 different meals: H (30 g honey), HA (30 g honey, 100 g almonds), HB (30 g honey, 125 g cheese, 10 g bread, 10 g butter). HA and HB contained the same amount of fat, but were different in fiber. No significant differences in the areas under glucose curves were observed. However, meal H produced earlier hyperglycemia than HA and HB (30 min: p less than 0.01). Insulin levels were higher after HB compared to H (p less than 0.05). Meals HA and HB were followed by higher triglyceride levels than H (p less than 0.05). It is concluded that: 1) honey and bread produce similar degrees of hyperglycemia in type II diabetics. 2) Fat-rich foods added to honey do not alter the total hyperglycemic effect but result in higher triglyceride and insulin serum concentrations.
Parabiosis is the surgical union of two animals to produce a chronic blood exchange. This model has previously been used to demonstrate the involvement of a blood-borne factor in the feedback control of food intake and regulation of energy balance. It has been hypothesized that obese rats produce a humoral agent that acts centrally to inhibit food intake and accumulation of fat. In this study 50-day-old male or female Zucker rats were joined in either lean-lean pairs or lean-obese pairs. They ate ad libitum until 152 days of age when body composition was determined. Parabiosis inhibited growth in all rats compared with single controls. Lean partners of obese rats had reduced carcass weights, the same percent body protein but less fat than members of lean-lean pairs. Female rats showed larger changes in body composition than did males. These results suggest that obese Zucker rats produce the hypothesized regulatory signal but do not respond to it.