Peter Raymond Flatt Dsc

Peter Raymond Flatt Dsc
Verified
Peter verified their affiliation via an institutional email.
Verified
Peter verified their affiliation via an institutional email.
University of Ulster

Professor

About

887
Publications
109,043
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
24,327
Citations
Additional affiliations
University of Ulster
Position
  • Research Director

Publications

Publications (887)
Article
Full-text available
Conditions like diabetes mellitus (DM), cancer, infections, inflammation, cardiovascular diseases (CVDs), and gastrointestinal (GI) disorders continue to have a major global impact on mortality and morbidity. Medicinal plants have been used since ancient times in ethnomedicine (e.g., Ayurveda, Unani, Traditional Chinese Medicine, and European Tradi...
Preprint
Full-text available
Conditions like diabetes mellitus (DM), cancer, infection, inflammation, cardiovascular diseases (CVDs) as well as gastrointestinal (GI) disorders continue to have a major global impact on mortality and morbidity. Medicinal plants have been used since ancient times in ethnomedicine (e.g. Ayurveda, Unani, Traditional Chinese Medicine, European Tradi...
Article
Full-text available
Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are related intestinal L-cell derived secretory products. GLP-1 has been extensively studied in terms of its influence on metabolism, but less attention has been devoted to GLP-2 in this regard. The current study compares the effects of these proglucagon-derived peptides on pancrea...
Article
Full-text available
Diabetes mellitus (DM) is currently regarded as a global public health crisis for which lifelong treatment with conventional drugs presents limitations in terms of side effects, accessibility, and cost. Type 2 diabetes (T2DM), usually associated with obesity, is characterized by elevated blood glucose levels, hyperlipidemia, chronic inflammation, i...
Poster
Full-text available
This study aims to compare the effects of GLP-1 and GLP-2 on pancreatic beta-cell function and turnover in vitro, along with their impact on glucose tolerance and appetite suppression in mice.
Article
Background: Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), are key products of the L-cell proglucagon-gene with diverse effects on metabolism. Whereas GLP-1 has been extensively studied, much less attention has been devoted to GLP-2. The current study directly compares the impact of GLP-1 and GLP-2 on pancreatic beta-cell func...
Article
Background Pancreatic islet β‐cell mass expands during pregnancy, but underlying mechanisms are not fully understood. This study examines the impact of pregnancy and cafeteria diet on islet morphology, associated cellular proliferation/apoptosis rates as well as β‐cell lineage. Methods Non‐pregnant and pregnant Ins 1 Cre/+ ; Rosa26‐eYFP transgenic...
Article
Aim To thoroughly investigate the impact of sustained neuropeptide Y4 receptor (NPY4R) activation in obesity‐associated diabetes. Methods Initially, the prolonged pharmacodynamic profile of the enzymatically stable pancreatic polypeptide (PP) analogue, [P ³ ]PP, was confirmed in normal mice up to 24 h after injection. Subsequent to this, [P ³ ]PP...
Preprint
Full-text available
Diabetes mellitus (DM) is currently regarded as a global public health crisis for which lifelong treatment with conventional drugs present limitations in terms of side effects, accessibility and cost. Type 2 diabetes (T2DM), usually associated with obesity, is characterized by elevated blood glucose levels, hyperlipidemia, chronic inflammation, imp...
Article
Full-text available
Recent approval of the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, tirzepatide, for the management of type 2 diabetes mellitus (T2DM) has reinvigorated interest in exploitation of GIP receptor (GIPR) pathways as a means of metabolic disease management. However, debate has long surrou...
Article
Objectives Dopamine and related receptors are evidenced in pancreatic endocrine tissue, but the impact on islet β-cell stimulus-secretion as well as (patho)physiological role are unclear. Methods The present study has evaluated islet cell signalling pathways and biological effects of dopamine, as well as alterations of islet dopamine in rodent mod...
Article
Pancreatic polypeptide (PP) is a postprandial hormone secreted from pancreatic islets that activates neuropeptide Y4 receptors (NPY4Rs). PP is known to induce satiety but effects at the level of the endocrine pancreas are less well characterized. In addition, rapid metabolism of PP by dipeptidyl peptidase‐4 (DPP‐4) limits the investigation of the e...
Chapter
Several amphibian peptides that were first identified on the basis of their antimicrobial or cytotoxic properties have subsequently shown potential for development into agents for the treatment of patients with Type 2 diabetes. A strategy is presented for the isolation and characterization of such peptides that are present in norepinephrine-stimula...
Article
Full-text available
Obesity and diabetes mellitus are prevalent metabolic disorders that have a detrimental impact on overall health. In this regard, there is now a clear link between these metabolic disorders and compromised bone health. Interestingly, both obesity and diabetes lead to elevated risk of bone fracture which is independent of effects on bone mineral den...
Article
Objective Momordica charantia, commonly known as bitter gourd, is traditionally used as remedies for various diseases including diabetes. The main objective of this study is to investigate the in vitro and in vivo insulinotropic and anti-diabetic effects of an 80% ethanolic extract of Momordica charantia (EEMC) fruit, as well as the underlying mole...
Article
Full-text available
Objective: Momordica charantia, commonly known as bitter gourd, is traditionally used as remedies for various diseases including diabetes. The main objective of this study is to investigate the in vitro and in vivo insulinotropic and anti-diabetic effects of an 80% ethanolic extract of Momordica charantia (EEMC) fruit, as well as the underlying mol...
Article
Aim Despite its abundance in pancreatic islets of Langerhans and proven antihyperglycemic effects, the impact of the essential amino acid, taurine, on islet β‐cell biology has not yet received due consideration, which prompted the current studies exploring the molecular selectivity of taurine import into β‐cells and its acute and chronic intracellu...
Conference Paper
The prevalence of type 2 diabetes (non-insulin dependent diabetes) has been universally acknowledged as a chronic public health concern and the leading cause of mortality on a global scale. Plant-based bioactive compounds have made significant contributions to the management of diabetes mellitus globally. Artocarpus heterophyllus, also known as “ka...
Article
The development of pancreatic islet endocrine cells is a tightly regulated process leading to the generation of distinct cell types harbouring different hormones in response to small changes in environmental stimuli. Cell differentiation is driven by transcription factors that are also critical for the maintenance of the mature islet cell phenotype...
Article
Effects of sustained activation of glucagon-like peptide-1 (GLP-1) receptors (GLP-1R) as well as antagonism of receptors for glucose-dependent insulinotropic peptide (GIP) on intestinal morphology and related gut hormone populations have not been fully investigated. The present study assesses the impact of 21-days twice daily treatment with the GLP...
Article
Full-text available
The present study examines differences in metabolic and pancreatic islet adaptative responses following streptozotocin (STZ) and hydrocortisone (HC) administration in male and female transgenic GluCreERT2/Rosa26-eYFP mice. Mice received 5 daily doses of STZ (50 mg/kg, i.p) or 10 daily doses of HC (70 mg/kg, i.p), with parameters assessed on day 11....
Article
Obesity is a major cause of infertility in females with a direct correlation between energy intake and reproductive dysfunction. To explore underlying mechanisms, disturbances in reproductive health and incretin/reproductive hormone receptor expression were studied in female Wistar rats fed a high-fat-diet for 20-weeks. Metabolic parameters and ova...
Article
Full-text available
Insulin regulates blood glucose levels, and is the mainstay for the treatment of type-1 diabetes and type-2 when other drugs provide inadequate control. Therefore, effective oral Insulin delivery would be a significant advance in drug delivery. Herein, we report the use of the modified cell penetrating peptide (CPP) platform, Glycosaminoglycan-(GAG...
Article
Insulin regulates blood glucose levels, and is the mainstay for the treatment of type-1 diabetes and type-2 when other drugs provide inadequate control. Therefore, effective oral Insulin delivery would be a significant advance in drug delivery. Herein, we report the use of the modified cell penetrating peptide (CPP) platform, Glycosaminoglycan-(GAG...
Article
Full-text available
Roux-en-Y gastric-bypass (RYGB) induced alterations in intestinal morphology and gut-cell hormone expression profile in the bypassed biliopancreatic-limb (BPL) versus the alimentary-limbs (AL) are poorly characterised. This pilot study has therefore explored effects following RYGB in high-fat-diet (HFD) and normal-diet (ND) rats. Female Wistar rats...
Poster
Background and Aims: Recent studies suggest that synthetic (such as cotadutide) and natural (oxyntomodulin) dual agonists of GLP-1 and glucagon receptors may become future key antidiabetic medications. The two signals amplify cAMP production in target cells, which, on the whole-body scale is reflected in the potentiation of insulin secretion withou...
Article
Objective: Glucagon receptor (GCGR) antagonism elicits antihyperglycemic effects in rodents and humans. The present study investigates whether the well characterised peptide-based GCGR antagonist, desHis1Pro4Glu9-glucagon (Lys12PAL), alters alpha-cell turnover or identity in mice. Methods: Multiple low-dose streptozotocin (STZ) treated (50 mg/kg...
Article
Introduction : Obesity is recognised as a major healthcare challenge. Following years of slow progress in discovery of safe, effective therapies for weight management, recent approval of the glucagon-like peptide 1 receptor (GLP-1R) mimetics, liraglutide and semaglutide, for obesity has generated considerable excitement. It is anticipated these age...
Article
Full-text available
Objectives: Within mammalian pancreatic islets, there are two major endocrine cell types, beta-cells which secrete insulin and alpha-cells which secrete glucagon. Whereas, insulin acts to lower circulating glucose, glucagon counters this by increasing circulating glucose via the mobilisation of glycogen. Synthalin A (Syn A) was the subject of much...
Article
Aims: Despite its high concentration in pancreatic islets of Langerhans and broad range of antihyperglycemic effects, the route facilitating the import of dietary taurine into pancreatic β-cell and mechanisms underlying its insulinotropic activity are unclear. We therefore studied the impact of taurine on beta-cell function, alongside that of othe...
Article
Background: Prolonged high fat feeding negatively impacts pancreatic and intestinal morphology. In this regard, direct effects of PYY(3-36) on intestinal cell and pancreatic islet morphometry are yet to be fully explored in the setting of obesity. Methods: We examined the influence of 21-days twice daily treatment with PYY(3-36) on these paramet...
Article
Aims: To assess the role of GPR120 in glucose metabolism and incretin regulation from enteroendocrine L- and K-cells with determination of the cellular localisation of GPR120 in intestinal tissue and clonal Glucagon-Like Peptide-1 (GLP-1)/Gastric Inhibitory Polypeptide (GIP) cell lines. Main methods: Anti-hyperglycaemic, insulinotropic and incre...
Thesis
Full-text available
Research presented in this thesis has revealed exciting possibilities for exploiting normal physiological mechanisms triggered by incretin and other gut hormones for treatment of diabetes. A major theme has been the design of different families of enzyme resistant forms of GIP, GLP-1, CCK and oxyntomodulin by modification or substitution of amino a...
Article
The semi‐essential ubiquitous amino acid taurine has been shown to alleviate obesity and hyperglycemia in humans; however, the pathways underlying the antidiabetic actions have not been characterized. We explored the effect of chronic taurine exposure on cell biology of pancreatic islets, in degenerative type 1‐like diabetes. The latter was modeled...
Article
Long-acting analogues of the naturally occurring incretin, glucagon-like peptide-1 (GLP-1) and those modified to interact also with receptors for glucose-dependent insulinotropic polypeptide (GIP) have shown high glucose-lowering and weight-lowering efficacy when administered by once-weekly subcutaneous injection. These analogues herald an exciting...
Article
Pancreatic polypeptide (PP), a member of the neuropeptide Y (NPY) family of peptides, is a hormone secreted from the endocrine pancreas with established actions on appetite regulation. Thus, through activation of hypothalamic neuropeptide Y4 (NPY4R or Y4) receptors PP induces satiety in animals and humans, suggesting potential anti-obesity actions....
Article
GPR55 has been recognized as a novel anti-diabetic target exerting positive effects on beta cell function and mass. This study evaluated the metabolic actions and therapeutic efficacy of GPR55 agonist abnormal cannabidiol (Abn-CBD) administered alone and in combination with sitagliptin in diet-induced obese-diabetic mice. Chronic effects of 21-day...
Article
Full-text available
Substantial evidence suggests crosstalk between reproductive and gut-axis but mechanisms linking metabolism and reproduction are still unclear. The present study evaluated the possible role of glucose-dependent-insulinotropic-polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1) in reproductive function by examining receptor distribution and the ef...
Conference Paper
Full-text available
Spirulina platensis (SP, Blue-green algae) have been accepted as a supplement for the treatment of pre and post diabetes. The present study investigated the effects of butanol fraction from ethanol extract of S. platensis on insulin release from BRIN BD11 cells, isolated mouse islets, and perfused rat pancreas, as well as glucose homeostasis in typ...
Presentation
cAMP-elevating incretin peptides have been shown to attain multiple antidiabetic effects ranging from promoting insulin secretion from pancreatic islet beta cells to inhibiting glucagon release from alpha cells. Elevation of cAMP has an inhibitory effect on glycolytic flux in hepatocytes, however, the distinct effect of incretins on glycolytic flux...
Article
Full-text available
Objectives The antimalarial drug artemether is suggested to effect pancreatic islet cell transdifferentiation, presumably through activation γ-aminobutyric acid receptors, but this biological action is contested. Methods We have investigated changes in α-cell lineage in response to 10-days treatment with artemether (100 mg/kg oral, once daily) on...
Article
Full-text available
Modification of gut-islet secretions after Roux-En-Y gastric bypass (RYBG) surgery contributes to its metabolic and anti-diabetic benefits. However, there is limited knowledge on tissue-specific hormone distribution post-RYGB surgery and how this compares with best medical treatment (BMT). In the present study, pancreatic and ileal tissues were exc...
Article
Absolute or relative hyperglucagonaemia is a characteristic of both Type 1 and Type 2 diabetes, resulting in fasting hyperglycaemia due in part to increased hepatic glucose production and lack of postprandial suppression of circulating glucagon concentrations. Consequently, therapeutics that target glucagon secretion or biological action may be eff...
Article
Full-text available
Discerning modification to the amino acid sequence of native glucagon can generate specific glucagon receptor (GCGR) antagonists, that include desHis1Pro4Glu9-glucagon and the acylated form desHis1Pro4Glu9(Lys12PAL)-glucagon. In the current study, we have evaluated the metabolic benefits of once daily injection of these peptide-based GCGR antagonis...
Article
Full-text available
Aim: The current study examines whether sequential administration of (d-Arg35 )-sea lamprey PYY(1-36) (SL-PYY) and the GLP-1 mimetic, liraglutide, has beneficial effects in diabetes. Methods: SL-PYY is an enzymatically stable neuropeptide Y1 receptor (NPY1R) agonist known to induce pancreatic beta-cell rest and improve overall beta-cell health....
Article
Full-text available
Diabetes mellitus is prevalent among women of reproductive age, and many women are left undiagnosed or untreated1. Gestational diabetes has profound and enduring effects on the long-term health of the offspring2,3. However, the link between pregestational diabetes and disease risk into adulthood in the next generation has not been sufficiently inve...
Article
Ablation of glucagon receptor (GCGR) signalling is a potential treatment option for diabetes, whilst glucagon-like peptide-1 (GLP-1) receptor agonists are clinically approved for both obesity and diabetes. There is a suggestion that GCGR blockade enhances GLP-1 secretion and action, whilst GLP-1 receptor activation is known to inhibit glucagon rele...
Article
Full-text available
In folklore, Heritiera fomes (H. fomes) has been extensively used in treatment of various ailments such as diabetes, cardiac and hepatic disorders. The present study aimed to elucidate the antidiabetic actions of hot water extract of H. fomes (HWHF), including effects on insulin release from BRIN BD11 cells and isolated mouse islets as well as gluc...
Article
Aim Poorly controlled diabetes is characterised by a partial or complete loss of pancreatic islet β-cells, which deprives the remaining islet cells of important β-cell-derived soluble signals, such as insulin or GABA. We aimed to dissect the role of the two signals in the development of islet α-cells, focusing specifically on α-/β-cell transdiffere...
Article
The Avpr1a (V1a) and Avpr1b (V1b) receptor selective, vasopressin (AVP) analogue, Ac3IV has been shown to improve metabolism and pancreatic islet structure in diabetes and insulin resistance. The present study further investigates these actions by assessing the ability of Ac3IV to protect against pancreatic islet architectural disturbances induced...
Article
Despite the rapidly increasing prevalence and associated costs of obesity, treatment options have remained remarkably limited. Some 650 million people are estimated to be living with obesity, but until recently the lipase inhibitor orlistat was the only mainstay pharmacological option, alongside dietary restriction. However, with FDA approval of th...
Article
Full-text available
Ac3IV (Ac-CYIQNCPRG-NH2) is an enzymatically stable vasopressin analogue that selectively activates Avpr1a (V1a) and Avpr1b (V1b) receptors. In the current study we have employed streptozotocin (STZ) diabetic transgenic Ins1Cre/+;Rosa26-eYFP and GluCreERT2;Rosa26-eYFP mice, to evaluate the impact of sustained Ac3IV treatment on pancreatic islet cel...
Article
The dual role of the pancreas as both an endocrine and exocrine gland is vital for food digestion and control of nutrient metabolism. The exocrine pancreas secretes enzymes into the small intestine aiding digestion of sugars and fats, whereas the endocrine pancreas secretes a cocktail of hormones into the blood, which is responsible for blood gluco...
Article
The long-acting glucagon-like peptide-1 receptor (GLP1R) agonist, semaglutide and the unimolecular glucose-dependent insulinotropic polypeptide receptor (GIPR)/GLP1R dual-agonist, tirzepatide have been successfully introduced as therapeutic options for patients with Type-2 diabetes (T2DM) and obesity. Proglucagon-derived peptides from phylogenetica...
Conference Paper
Heritiera fomes (Sundari) have been accepted as a supplement for the treatment of pre and post diabetes. The present study investigated the effects of ethanol extract of H. fomes (EEHF) on insulin release from clonal pancreatic β-cells and mouse islets and protein glycation, starch digestion, glucose diffusion, DPP-IV enzyme activity in vitro and g...
Article
Clinically approved for the treatment of diabetes and obesity, glucagon‐like peptide‐1 (GLP‐1) receptor agonists display prominent glucose‐ and weight‐lowering effects as well as positive cardio‐ and neuro‐protective actions. Despite these benefits, bariatric surgery remains superior in producing robust and sustained weight loss alongside improveme...
Article
Full-text available
Neurotensin and xenin possess antidiabetic potential, mediated in part through augmentation of incretin hormone, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), action. In this study, fragment peptides of neurotensin and xenin, acetyl-neurotensin (8-13) and xenin-8-Gln, were fused together to create Ac-NT/XN-...
Article
Full-text available
Acacia arabica is used traditionally to treat a variety of ailments, including diabetes. This study elucidated the antidiabetic actions of A. arabica bark together with the isolation of bioactive molecules. Insulin secretion and signal transduction were measured using clonal β cells and mouse islets. Glucose uptake was assessed using 3T3-L1 adipocy...
Article
Aim: Evidence suggests beneficial metabolic effects of the nonapeptide hormone, arginine vasopressin (AVP), on metabolism, as also observed recently with the closely related oxytocin peptide. Materials and methods: In the current study we have exchanged selected amino acids at position 3 and 8 of AVP, namely phenylalanine and arginine, with thos...
Article
Full-text available
Aims Metformin, rosiglitazone and sulfonylureas enhance either insulin action or secretion and thus have been used extensively as early stage anti-diabetic medication, independently of the aetiology of the disease. When administered to newly diagnosed diabetes patients, these drugs produce variable results. Here, we examined the effects of the thre...
Article
Full-text available
Initially discovered as an impurity in insulin preparations, our understanding of the hyperglycaemic hormone glucagon has evolved markedly over subsequent decades. With description of the precursor proglucagon, we now appreciate that glucagon was just the first proglucagon-derived peptide (PGDP) to be characterised. Other bioactive members of the P...
Article
Full-text available
Combined activation of GLP-1 and CCK1 receptors has potential to synergistically augment the appetite-suppressive and glucose homeostatic actions of the individual parent peptides. In the current study, pancreatic beta-cell benefits of combined GLP-1 and CCK1 receptor upregulation were established, before characterising bioactivity and antidiabetic...