[Show abstract][Hide abstract] ABSTRACT: Nutrient restriction during the early stages of life usually leads to alterations in glucose homeostasis, mainly insulin secretion and sensitivity, increasing the risk of metabolic disorders in adulthood. Despite growing evidence regarding the importance of insulin clearance during glucose homeostasis in health and disease, no information exists about this process in malnourished animals. Thus, in the present study, we aimed to determine the effect of a nutrient-restricted diet on insulin clearance using a model in which 30-d-old C57BL/6 mice were exposed to a protein-restricted diet for 14 weeks. After this period, we evaluated many metabolic variables and extracted pancreatic islet, liver, gastrocnemius muscle (GCK) and white adipose tissue samples from the control (normal-protein diet) and restricted (low-protein diet, LP) mice. Insulin concentrations were determined using RIA and protein expression and phosphorylation by Western blot analysis. The LP mice exhibited lower body weight, glycaemia, and insulinaemia, increased glucose tolerance and altered insulin dynamics after the glucose challenge. The improved glucose tolerance could partially be explained by an increase in insulin sensitivity through the phosphorylation of the insulin receptor/protein kinase B and AMP-activated protein kinase/acetyl-CoA carboxylase in the liver, whereas the changes in insulin dynamics could be attributed to reduced insulin secretion coupled with reduced insulin clearance and lower insulin-degrading enzyme (IDE) expression in the liver and GCK. In summary, protein-restricted mice not only produce and secrete less insulin, but also remove and degrade less insulin. This phenomenon has the double benefit of sparing insulin while prolonging and potentiating its effects, probably due to the lower expression of IDE in the liver, possibly with long-term consequences.
[Show abstract][Hide abstract] ABSTRACT: Aim: Glucose homeostasis is maintained under strict physiological control in which the central nervous system is very important. Ketamine/xylazine mixture induces hyperglycemia, although the mechanism involved is unknown. We aimed to study the role of sympathoadrenal axis on glycemia and insulinemia in adult rats. Methods: NInety-day-old male Wistar rats were used. Half of the rats underwent removal of the adrenal gland medullae (adrenodemedullation, ADM). After overnight fasting, all rats were given the intravenous glucose tolerance test (ivGTT), which was performed in six groups: awake, ketamine/xylazine (KX) and thiopental (Thiop) anesthetized intact rats, and the same groups of ADM rats. The intraperitoneal insulin tolerance test (1U/kg BW) was performed in an additional animal group to record the rate constant of plasma glucose disappearance (Kitt). Tissue insulin sensitivity was also evaluated by the homeostasis model assessment (HOMA). Results: Ketamine/xylazine increased basal glycemia by 110.6% (P<0.001) in intact rats. In the ADM group, KX rats had a reduction of 36.6% (P<0.05) basal glycemia. Thiop caused a decrease of 70.3% (P<0.05) in basal insulinemia in intact rats. ADM reduced fasting insulin in all groups. Insulin sensitivity was elevated in intact Thiop rats, while insulin resistance was observed in intact KX rats. Both anesthetics induced glucose intolerance during ivGTT in the intact group, but not in ADM rats. Insulin secretion was reduced for both anesthetics in intact and ADM rats. Conclusion: Sympathoadrenal axis activity is not involved with the hyperglycemia induced by thiopental or ketamine/xylazine.
[Show abstract][Hide abstract] ABSTRACT: AIMS: Glucagon-like peptide-1 (GLP-1) is an important modulator of insulin secretion by endocrine pancreas. In the present study we investigated the effect of swim training on GLP-1 insulinotropic action in pancreatic islets from monosodium glutamate (MSG)-obese rats. METHODS: Obesity was induced by neonatal MSG administration. MSG-obese and control (CON) exercised rats swam for 30 min (3 times/week) for 10 weeks. Pancreatic islets were isolated by colagenase technique and incubated with low (5.6 mM) or high (16.7 mM) glucose concentrations in the presence or absence of GLP-1 (10 nM). In addition, GLP-1 gene expression in ileum was quantified in fasting and glucose conditions. RESULTS: Exercise reduced obesity and hyperinsulinemia in MSG-obese rats. Swim training also inhibited glucose-induced insulin secretion in islets from both groups. Islets from MSG-obese rats maintained GLP-1 insulinotropic response in low glucose concentration. In contrast, in the presence of high glucose concentration GLP-1 insulinotropic action was absent in islets from MSG-obese rats. Islets from MSG-exercised rats showed reduced GLP-1 insulinotropic action in the presence of low glucose. However, in high glucose concentration swim training restored GLP-1 insulinotropic response in islets from MSG-obese rats. In all groups, glucose intake increased GLP-1immunoreactivity and gene expression in ileum cells in relation at fasting conditions. Swim training reduced these parameters only in ileum cells from CON-exercised rats. Neither MSG treatment nor exercise affected GLP-1 expression in the ileum. CONCLUSIONS: Exercise avoids insulin hypersecretion restoring GLP-1's insulinotropic action in pancreatic islets from MSG-obese rats. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Monosodium glutamate-obese rats are glucose intolerant and insulin resistant. Their pancreatic islets secrete more insulin at increasing glucose concentrations, despite the possible imbalance in the autonomic nervous system of these rats. Here, we investigate the involvement of the cholinergic/protein kinase (PK)-C and PKA pathways in MSG β-cell function. Male newborn Wistar rats received a subcutaneous injection of MSG (4 g/kg body weight (BW)) or hyperosmotic saline solution during the first 5 days of life. At 90 days of life, plasma parameters, islet static insulin secretion and protein expression were analyzed. Monosodium glutamate rats presented lower body weight and decreased nasoanal length, but had higher body fat depots, glucose intolerance, hyperinsulinemia and hypertrigliceridemia. Their pancreatic islets secreted more insulin in the presence of increasing glucose concentrations with no modifications in the islet-protein content of the glucose-sensing proteins: the glucose transporter (GLUT)-2 and glycokinase. However, MSG islets presented a lower secretory capacity at 40 mM K(+) (P < 0.05). The MSG group also released less insulin in response to 100 μM carbachol, 10 μM forskolin and 1 mM 3-isobutyl-1-methyl-xantine (P < 0.05, P < 0.0001 and P < 0.01). These effects may be associated with a the decrease of 46 % in the acetylcholine muscarinic type 3 (M3) receptor, and a reduction of 64 % in PKCα and 36 % in PKAα protein expressions in MSG islets. Our data suggest that MSG islets, whilst showing a compensatory increase in glucose-induced insulin release, demonstrate decreased islet M3/PKC and adenylate cyclase/PKA activation, possibly predisposing these prediabetic rodents to the early development of β-cell dysfunction.
[Show abstract][Hide abstract] ABSTRACT: Changes in glucose levels mobilize a neuroendocrine response that prevents or corrects glycemia. The hypothalamus is the main area of the brain that regulates glycemic homeostasis. Metabolic diseases, such as obesity and diabetes, are related to imbalance of this control. The modulation of autonomic nervous system (ANS) activity is mediated by neuronal hypothalamic pathways. In the present work, we investigate whether glucose concentration in the hypothalamic area changes ANS activity.
Glucose was administered intracerebroventricularly to 90-day-old rats, and samples of blood were collected during brain glucose infusion to measure the blood glucose and insulin levels. The electric activity of the superior vagus nerve and superior sympathetic ganglion was directly registered.
Glucose 5·6 mM infused in the hypothalamus induced a 67·6% decrease in blood insulin concentration compared to saline infusion (P<0·01); however, no glycemia changes occurred. During glucose 5·6 mM intracerebroventricular infusion, the firing rate of the vagus nerve was decreased 39% and sympathetic nerve activity was increased 177% compared to saline infusion (P<0·01).
Glucose injection into the brain in the hypothalamic area modulates glucose homeostasis, which might be mediated by the sensitivity of the hypothalamic area to local changes in glucose concentration. We suggest that gluconeurons in the hypothalamus contribute to the control of glycemia through ANS activity.
Neurological Research 01/2013; 35(1):15-21. · 1.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Feeding behavior is a major determinant of body composition, adiposity, and glucose homeostasis. Both obesity and malnutrition are risk factors for the metabolic syndrome and are associated with altered food intake. Here we assessed the effects of taurine (TAU) supplementation upon adiposity, food intake, and central insulin signaling in malnourished mice fed on a high-fat diet (HFD). Weaned male C57BL/6 mice were fed a control (14% protein-C) or a protein-restricted (6% protein-R) diet. After 6 weeks, both groups received or not HFD for 8 weeks (CH and RH). Half of the HFD groups were supplemented with 5% TAU (CHT and RHT). Both HFD groups were overweight and showed increased perigonadal and retroperitoneal fat pads. TAU supplementation attenuated obesity in CHT but not in RHT mice. HFD induced hypercholesterolemia and glucose intolerance, although only CH group presented fasting hyperglycemia. TAU supplementation also improved glucose homeostasis only in CHT mice. Western blot analysis showed a reduction of 55% in CH hypothalamic content of phosphorylated IRS-1 (pIRS-1) at basal condition compared with C. TAU treatment increased 35% Akt phosphorylation levels in CHT without modification in RHT hypothalamus. However, TAU supplementation did not alter hypothalamic pIRS-1 amount. CH and RH mice presented increased calorie intake that was normalized in CHT but not in RHT. In conclusion, mice fed on an HFD developed obesity, hypercholesterolemia, glucose intolerance, and increased calorie intake. TAU promoted increased hypothalamic insulin action only in CH mice which was linked to prevention of overfeeding, obesity, and glucose intolerance. Protein-restriction promoted metabolic damages that were not prevented by TAU supplementation.
Advances in experimental medicine and biology 01/2013; 776:93-103. · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Whey protein (WP) and whey protein hydrolysate (WPH) have the recognized capacity to increase glycogen stores. The objective of this study was to verify if consuming WP and WPH could also increase the concentration of the glucose transporters GLUT-1 and GLUT-4 in the plasma membrane (PM) of the muscle cells of sedentary and exercised animals. Forty-eight Wistar rats were divided into 6 groups (n = 8 per group), were treated and fed with experimental diets for 9 days as follows: a) control casein (CAS); b) WP; c) WPH; d) CAS exercised; e) WP exercised; and f) WPH exercised. After the experimental period, the animals were sacrificed, muscle GLUT-1 and GLUT-4, p85, Akt and phosphorylated Akt were analyzed by western blotting, and the glycogen, blood amino acids, insulin levels and biochemical health indicators were analyzed using standard methods. Consumption of WPH significantly increased the concentrations of GLUT-4 in the PM and glycogen, whereas the GLUT-1 and insulin levels and the health indicators showed no alterations. The physical exercise associated with consumption of WPH had favorable effects on glucose transport into muscle. These results should encourage new studies dealing with the potential of both WP and WPH for the treatment or prevention of type II diabetes, a disease in which there is reduced translocation of GLUT-4 to the plasma membrane.
PLoS ONE 01/2013; 8(8):e71134. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: SCOPE: Poor nutrition during the perinatal period is associated with an increased risk for metabolic syndrome in adulthood. Taurine (TAU) regulates β-cell function and glucose homeo-stasis. Here, we assessed the effects of TAU supplementation upon adiposity and glucose control in malnourished mice fed a high-fat diet (HFD). METHODS AND RESULTS: Weaned male C57BL/6J mice were fed a control (14% protein - C) or a protein-restricted (6% protein - R) diet for 6 weeks. Afterwards, mice received or not an HFD for 8 weeks (CH and RH). Half of the HFDmice were supplemented with 5% TAU after weaning (CHT and RHT). Protein restriction led to typical malnutrition features. HFD increased body weight, adiposity, and led to hyperleptinemia, hyperphagia, glucose intolerance, and higher liver glucose output in RH and CH groups. Fasted R mice showed higher plasma adiponectin levels and increased phosphorylation of the AMP-activated protein kinase (p-AMPK) in the liver. These parameters were reduced in RH mice and increased p-AMPK persisted in RHT. TAU prevented obesity and improved glucose tolerance only in CHT, but liver glucose control was ameliorated in both supplemented groups. Better CHT liver glucose control was linked to increased Akt (thymoma viral proto-oncogene/protein kinase B) phosphorylation. CONCLUSION: Malnourished mice fed an HFD developed obesity, glucose intolerance, and increased liver glucose output. TAU preserved only normal liver glucose control in RHT mice, an effect associated with increased liver p-AMPK content.
Molecular Nutrition & Food Research 12/2012; · 4.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was determine whether the introduction of a high-fat diet during the peripubertal phase induces significant changes in body weight control, glucose homeostasis and the parasympathetic tonus compared with the administration of this diet to adult rats. High-fat diet was offered to male Wistar rats at weaning or during adulthood. A group of rats received high-fat diet for 60 days, from weaning to 81-day-old (HF81) or from 60 to 120-day-old (HF120), whereas 2 other groups received a normal-fat diet (i. e., NF81 and NF120). We analyzed adiposity, glucose homeostasis, insulin sensitivity, and vagal nerve activity. High-fat diet increased the accumulation of adipose tissue in all of the rats, but the difference was greater in the rats that were fed the high-fat diet since weaning (p<0.001). The HF rats showed glucose intolerance with high levels of insulin secretion during the glucose tolerance test (p<0.01). Rats that were fed the high-fat diet presented severe insulin resistance, indicated by a low K itt (p<0.01). Interestingly, the HF81 rats exhibited greater insulin resistance compared with the HF120 rats (p<0.05). The recordings of vagus nerve activity showed that the HF rats had higher parasympathetic activity than the NF rats irrespective of age (p<0.01). Our results show that a high-fat diet offered to rats just after weaning or in adulthood both cause impairment of glycemic homeostasis and imbalance in parasympathetic activity. Importantly, the consumption of high-fat diet immediately after weaning has more drastic consequences compared with the consumption of the same diet during adulthood.
Hormone and Metabolic Research 03/2012; 44(6):458-64. · 2.15 Impact Factor