Glucagon-like peptide-1: a major regulator of pancreatic beta-cell function

Perfetti, Riccardo; Merkel, Patricia

doi:10.1530/eje.0.1430717

Cited by 125 publications

(80 citation statements)

References 58 publications

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“…10,11 GLP-1 stimulates the formation of the second messenger, cAMP, which activates a cAMP-dependent protein kinase and phosphorylation of key proteins in the control of insulin secretion. 12,35 The binding of GLP-1 to its receptor also depolarizes the cellular membrane and induces a rise in free intracellular calcium concentration, followed by a potentiation of the glucose-induced insulin secretion dependent upon extracellular sodium. 16 In addition to the insulin stimulatory effect, GLP-1 may affect the hepatic insulin extraction.…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15][16] Recent evidence suggests that GLP-1 may also promote regeneration of islet cells and expansion of the b-cell mass. 12,17 Racial differences in GLP-1 concentrations in obese subjects have not been previously reported. Based on GLP-1's effect on b-cell function and insulin secretion, we assessed whether differences in GLP-1 levels may account for the increased b-cell activity, insulin concentrations, and decreased insulin clearance in obese AAs.…”

mentioning

confidence: 90%

“…10,11 In addition to stimulating insulin secretion, GLP-1 has been shown to have other profound biological effects on b-cells. 12 GLP-1 regulates b-cell function by maintaining a portion of the b-cell population in a glucose-competent state by making resistant islets glucose sensitive. [13][14][15][16] Recent evidence suggests that GLP-1 may also promote regeneration of islet cells and expansion of the b-cell mass.…”

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confidence: 99%

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Racial differences in glucagon-like peptide-1 (GLP-1) concentrations and insulin dynamics during oral glucose tolerance test in obese subjects

et al. 2003

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Obese African-American (AA) subjects have higher resting and stimulated insulin concentrations than obese Caucasians (C), which could not be explained by the severity of obesity or the degree of insulin sensitivity. We investigated whether differences in glucagon-like peptide-1 (GLP-1), the most potent incretin that regulates insulin secretion, might explain racial differences in insulin response. Accordingly, we measured fasting and stimulated glucose, insulin, and GLP-1 levels during a 3-h oral glucose tolerance test (OGTT) in 26 obese C (age 3872 y, body mass index 4471 kg/m 2 ) and 16 obese AA (age 3672 y, BMI 4672 kg/ m 2 ) subjects. Corrected insulin response (CIR 30 ), a measure of b-cell activity, whole body insulin sensitivity index (WBISI), and area under the curve (AUC) for insulin, GLP-1, and C-peptide/insulin ratio were computed from the OGTT. Glucose levels, fasting and during the OGTT, were similar between racial groups; 32% of the C and 31% of the AA subjects had impaired glucose tolerance. Keywords: GLP-1; insulin; racial; b-cell activity Obesity is characterized by hyperinsulinemia and increased insulin resistance. 1 Several in vitro and in vivo studies have shown that hyperinsulinemia may play an important role in the pathogenesis of obesity through regulation of appetite, fat cell metabolism, and energy expenditure. 2-4 Recent different cross-sectional and longitudinal studies have reported that both lean and obese African Americans (AA) exhibit higher fasting and stimulated insulin levels when compared with their white counterparts. 5,6 Several studies have reported increased b-cell activity as the primary mechanism for this hyperinsulinemic state in black patients; 6 while others, have suggested that the hyperinsulinemia is the result of decreased hepatic insulin clearance 7 and reduced insulin sensitivity. 8 Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide gastric inhibitory polypeptide (GIP) are the two most important incretins. 9 In humans, GLP-1 results from post-translational processing of proglucagon in the intestinal L-cells and accounts for 80% of the intestinal incretin effect. 10 GLP-1's action is mediated by its binding to cell surface receptors (GLP-1R) that are highly expressed on the cell membranes of pancreatic b-cells. 10,11 In addition to stimulating insulin secretion, GLP-1 has been shown to have other profound biological effects on b-cells. 12 GLP-1 regulates b-cell function by maintaining a portion of the b-cell population in a glucose-competent state by making resistant islets glucose sensitive. [13][14][15][16] Recent evidence suggests that GLP-1 may also promote regeneration of islet cells and expansion of the b-cell mass. 12,17 Racial differences in GLP-1 concentrations in obese subjects have not been previously reported. Based on GLP-

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 90%

mentioning

confidence: 99%

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Racial differences in glucagon-like peptide-1 (GLP-1) concentrations and insulin dynamics during oral glucose tolerance test in obese subjects

et al. 2003

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“…GLP-1 also has tropic effects, including pancreatic b-cell proliferation and neurogenesis as well as an inhibition of b-cell apoptosis (Brubaker & Drucker 2004). However, the clinical application of GLP-1 is limited because of its short duration of action due to rapid degradation by dipeptidyl peptidase IV (Perfetti & Merkel 2000). Exendin-4, a naturally occurring more potent and stable analog of GLP-1 that selectively binds to the GLP-1 receptor, is clinically used to treat type II diabetes mellitus .…”

Section: Introductionmentioning

confidence: 99%

Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease

Kim

Moon²,

Park

2009

Journal of Endocrinology

225

179

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Exendin-4 is a naturally occurring more potent and stable analog of glucagon-like peptide-1 (GLP-1) that selectively binds at the GLP-1 receptor. It has been recently demonstrated that GLP-1 receptor stimulation preserves dopaminergic neurons in cellular and rodent models of Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity in rodents; previous studies suggest that activated microglia actively participate in the pathogenesis of PD neurodegeneration. However, the role of microglia in the neuroprotective properties of exendin-4 is still unknown. Here, we show that, in the mouse MPTP PD model, systemic administration of exendin-4 significantly attenuates the loss of substantia nigra pars compacta (SNpc) neurons and the striatal dopaminergic fibers. Exendin-4 prevents MPTP-induced microglial activation in the SNpc and striatum, and the expression of matrix metalloproteinase-3. In addition, exendin-4 also suppressed MPTP-induced expression of pro-inflammatory molecules and tumor necrosis factor a and interleukin-1b. Our data indicate that exendin-4 may act as a survival factor for dopaminergic neurons by functioning as a microgliadeactivating factor and suggest that exendin-4 may be a valuable therapeutic agent for neurodegenerative diseases such as PD.

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“…The most important marker was the fatty acid binding protein, involved in the fixation, transport and intracellular metabolism of long chain fat acids, which have also been linked to the development of diabetes, obesity, insulin resistance and metabolic syndrome. C reactive protein, GLP-1 and the pancreatic polypeptide were also involved in the development of insulin resistance [9]. It is therefore evident that in patients with Mexican ancestry the development of AD is linked to diabesity and metabolic syndrome.…”

Section: Diabesity and Neurodegenerative Diseases In The Hispanic Patmentioning

confidence: 99%

Diabetes, Neurodegenerative Diseases, GLP-1 & Surgery: Evidence Calls for Exploration

Kunz-Martinez¹

2017

EMIJ

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Glucagon-like peptide-1: a major regulator of pancreatic beta-cell function

Cited by 125 publications

References 58 publications

Racial differences in glucagon-like peptide-1 (GLP-1) concentrations and insulin dynamics during oral glucose tolerance test in obese subjects

Racial differences in glucagon-like peptide-1 (GLP-1) concentrations and insulin dynamics during oral glucose tolerance test in obese subjects

Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease

Diabetes, Neurodegenerative Diseases, GLP-1 & Surgery: Evidence Calls for Exploration

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