The effect of glucose and glucagon-like peptide-1 stimulation on insulin release in the perfused pancreas in a non—insulin-dependent diabetes mellitus animal model

Shen, Hua-Qiong; Roth, Mark D.; Peterson, Richard G.

doi:10.1016/s0026-0495(98)90275-x

Cited by 10 publications

(8 citation statements)

References 35 publications

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“…This is similar to the progressive loss of glucose-stimulated insulin secretion in human type 2 diabetes, and thus ZDF rats represent a good animal model for this form of human diabetes (16). Interestingly, GLP-1 retains its potency of enhancing glucose-stimulated insulin release in prediabetic and diabetic ZDF rats (17,18), and chronic administration of exendin-4, a peptide showing agonistic activity at the GLP-1 receptor, demonstrated antidiabetic efficacy in these animals, improving glycemic control and insulin sensitivity (19). Similarly, in type 2 diabetic patients, GLP-1 has been successfully used to normalize fasting and prandial glycemia (20 -23).…”

mentioning

confidence: 69%

Chronic Inhibition of Circulating Dipeptidyl Peptidase IV by FE 999011 Delays the Occurrence of Diabetes in Male Zucker Diabetic Fatty Rats

et al. 2002

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Acute suppression of dipeptidyl peptidase IV (DPP-IV) activity improves glucose tolerance in the Zucker fatty rat, a rodent model of impaired glucose tolerance, through stabilization of glucagon-like peptide (GLP)-1. This study describes the effects of a new and potent DPP-IV inhibitor, FE 999011, which is able to suppress plasma DPP-IV activity for 12 h after a single oral administration. In the Zucker fatty rat, FE 999011 dose-dependently attenuated glucose excursion during an oral glucose tolerance test and increased GLP-1(7-36) release in response to intraduodenal glucose. Chronic treatment with FE 999011 (10 mg/kg, twice a day for 7 days) improved glucose tolerance, as suggested by a decrease in the insulin-to-glucose ratio. In the Zucker diabetic fatty (ZDF) rat, a rodent model of type 2 diabetes, chronic treatment with FE 999011 (10 mg/kg per os, once or twice a day) postponed the development of diabetes, with the twice-a-day treatment delaying the onset of hyperglycemia by 21 days. In addition, treatment with FE 999011 stabilized food and water intake to prediabetic levels and reduced hypertriglyceridemia while preventing the rise in circulating free fatty acids. At the end of treatment, basal plasma GLP-1 levels were increased, and pancreatic gene expression for GLP-1 receptor was significantly upregulated. This study demonstrates that DPP-IV inhibitors such as FE 999011 could be of clinical value to delay the progression from impaired glucose tolerance to type 2 diabetes.

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confidence: 69%

Chronic Inhibition of Circulating Dipeptidyl Peptidase IV by FE 999011 Delays the Occurrence of Diabetes in Male Zucker Diabetic Fatty Rats

et al. 2002

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“…A 48-h infusion of native GLP-1 lowered blood glucose in association with increased levels of circulating insulin, islet insulin content, and insulin mRNA in Wistar rats aged 22 months (100), and perfused pancreas studies have demonstrated GLP-1-dependent augmentation of insulin secretion in ZDF rats of diverse genetic backgrounds (101)(102)(103). Similarly, exendin-4 lowered glucose in db/db and ob/ob mice, ZDF rats, and diabetic rhesus monkeys in acute and chronic experiments (78,104,105) and the GLP-1 analog NN211 improved glycemic control in pigs, rats, and mice (60,81,106).…”

Section: Glp-1r Agonists and Experimental Models Of Diabetesmentioning

confidence: 99%

Enhancing Incretin Action for the Treatment of Type 2 Diabetes

2003

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OBJECTIVE—To examine the mechanisms of action, therapeutic potential, and challenges inherent in the use of incretin peptides and dipeptidyl peptidase-IV (DPP-IV) inhibitors for the treatment of type 2 diabetes. RESEARCH DESIGN AND METHODS—The scientific literature describing the biological importance of incretin peptides and DPP-IV inhibitors in the control of glucose homeostasis has been reviewed, with an emphasis on mechanisms of action, experimental diabetes, human physiological experiments, and short-term clinical studies in normal and diabetic human subjects. RESULTS—Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) exert important effects on β-cells to stimulate glucose-dependent insulin secretion. Both peptides also regulate β-cell proliferation and cytoprotection. GLP-1, but not GIP, inhibits gastric emptying, glucagon secretion, and food intake. The glucose-lowering actions of GLP-1, but not GIP, are preserved in subjects with type 2 diabetes. However, native GLP-1 is rapidly degraded by DPP-IV after parenteral administration; hence, degradation-resistant, long-acting GLP-1 receptor (GLP-1R) agonists are preferable agents for the chronic treatment of human diabetes. Alternatively, inhibition of DPP-IV–mediated incretin degradation represents a complementary therapeutic approach, as orally available DPP-IV inhibitors have been shown to lower glucose in experimental diabetic models and human subjects with type 2 diabetes. CONCLUSIONS—GLP-1R agonists and DPP-IV inhibitors have shown promising results in clinical trials for the treatment of type 2 diabetes. The need for daily injections of potentially immunogenic GLP-1–derived peptides and the potential for unanticipated side effects with chronic use of DPP-IV inhibitors will require ongoing scrutiny of the risk-benefit ratio for these new therapies as they are evaluated in the clinic.

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“…The insulinotropic effect of GLP-1 on the pancreas has been demonstrated to be preserved in animal models of diabetes by stimulating insulin exocytosis (Shen et al, 1998; Drucker, 2001; MacDonald et al, 2002), and promoting insulin biosynthesis (Fehmann and Habener, 1992; Perfetti and Merkel, 2000; Moon et al, 2011). Recently, direct effects of GLP-1 on growth, survival (Xu et al, 1999; Stoffers et al, 2000; List and Habener, 2004), and differentiation of β-cells have been reported (Drucker, 2003).…”

Section: Introductionmentioning

confidence: 99%

Structural and Molecular Conservation of Glucagon-Like Peptide-1 and Its Receptor Confers Selective Ligand-Receptor Interaction

Moon¹,

Park²,

Kim³

et al. 2012

Front. Endocrin.

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Glucagon-like peptide-1 (GLP-1) is a major player in the regulation of glucose homeostasis. It acts on pancreatic beta cells to stimulate insulin secretion and on the brain to inhibit appetite. Thus, it may be a promising therapeutic agent for the treatment of type 2 diabetes mellitus and obesity. Despite the physiological and clinical importance of GLP-1, molecular interaction with the GLP-1 receptor (GLP1R) is not well understood. Particularly, the specific amino acid residues within the transmembrane helices and extracellular loops of the receptor that may confer ligand-induced receptor activation have been poorly investigated. Amino acid sequence comparisons of GLP-1 and GLP1R with their orthologs and paralogs in vertebrates, combined with biochemical approaches, are useful to determine which amino acid residues in the peptide and the receptor confer selective ligand-receptor interaction. This article reviews how the molecular evolution of GLP-1 and GLP1R contributes to the selective interaction between this ligand-receptor pair, providing critical clues for the development of potent agonists for the treatment of diabetes mellitus and obesity.

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The effect of glucose and glucagon-like peptide-1 stimulation on insulin release in the perfused pancreas in a non—insulin-dependent diabetes mellitus animal model

Cited by 10 publications

References 35 publications

Chronic Inhibition of Circulating Dipeptidyl Peptidase IV by FE 999011 Delays the Occurrence of Diabetes in Male Zucker Diabetic Fatty Rats

Chronic Inhibition of Circulating Dipeptidyl Peptidase IV by FE 999011 Delays the Occurrence of Diabetes in Male Zucker Diabetic Fatty Rats

Enhancing Incretin Action for the Treatment of Type 2 Diabetes

Structural and Molecular Conservation of Glucagon-Like Peptide-1 and Its Receptor Confers Selective Ligand-Receptor Interaction

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