Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2

Brubaker, Patricia L.; Anini, Younès

doi:10.1139/y03-107

Cited by 189 publications

(124 citation statements)

References 81 publications

Supporting

Mentioning

123

Contrasting

Order By: Relevance

“…Ingested nutrients, especially fats and carbohydrates, stimulate GLP1 secretion by indirect, duodenally activated neurohumoral mechanisms, as well as by direct contact within the distal intestine (49). The two equipotent bioactive forms, GLP1 7-36 amide and GLP1 , are rapidly inactivated in the circulation by dipeptidyl peptidase-4 (DPP4) (50).…”

Section: Lower-intestinal Satiation: Glucagon-like Peptide-1mentioning

confidence: 99%

Gastrointestinal regulation of food intake

Cummings¹,

Overduin²

2007

J. Clin. Invest.

1,011

827

View full text Add to dashboard Cite

Despite substantial fluctuations in daily food intake, animals maintain a remarkably stable body weight, because overall caloric ingestion and expenditure are exquisitely matched over long periods of time, through the process of energy homeostasis. The brain receives hormonal, neural, and metabolic signals pertaining to body-energy status and, in response to these inputs, coordinates adaptive alterations of energy intake and expenditure. To regulate food consumption, the brain must modulate appetite, and the core of appetite regulation lies in the gut-brain axis. This Review summarizes current knowledge regarding the neuroendocrine regulation of food intake by the gastrointestinal system, focusing on gastric distention, intestinal and pancreatic satiation peptides, and the orexigenic gastric hormone ghrelin. We highlight mechanisms governing nutrient sensing and peptide secretion by enteroendocrine cells, including novel taste-like pathways. The increasingly nuanced understanding of the mechanisms mediating gut-peptide regulation and action provides promising targets for new strategies to combat obesity and diabetes.

show abstract

Section: Lower-intestinal Satiation: Glucagon-like Peptide-1mentioning

confidence: 99%

Gastrointestinal regulation of food intake

Cummings¹,

Overduin²

2007

J. Clin. Invest.

1,011

827

View full text Add to dashboard Cite

show abstract

“…Intestinal injury and resection are both associated with elevated circulating levels of PGDPs and increased levels of proglucagon mRNA in the remnant intestine (29,30). PGDP secretion by enteroendocrine L cells is stimulated by neural signals, peptide hormones such as GIP (in rodents but not humans), and direct nutrient contact (31).…”

Section: The Proglucagon-derived Peptidesmentioning

confidence: 99%

The role of gut hormones in glucose homeostasis

Drucker¹

2007

J. Clin. Invest.

544

409

View full text Add to dashboard Cite

The gastrointestinal tract has a crucial role in the control of energy homeostasis through its role in the digestion, absorption, and assimilation of ingested nutrients. Furthermore, signals from the gastrointestinal tract are important regulators of gut motility and satiety, both of which have implications for the long-term control of body weight. Among the specialized cell types in the gastrointestinal mucosa, enteroendocrine cells have important roles in regulating energy intake and glucose homeostasis through their actions on peripheral target organs, including the endocrine pancreas. This article reviews the biological actions of gut hormones regulating glucose homeostasis, with an emphasis on mechanisms of action and the emerging therapeutic roles of gut hormones for the treatment of type 2 diabetes mellitus.

show abstract

“…The incretin hormone glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide that is secreted from the intestinal L cells in response to nutrient ingestion [7,8]. This peptide and its long-acting receptor agonist, exendin-4 [9], possess a variety of actions that are protective against diabetes and that are mediated at the level of the beta cell, as well as in peripheral tissues.…”

Section: Introductionmentioning

confidence: 99%

Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B

et al. 2005

View full text Add to dashboard Cite

Aims/hypothesis: The gut hormone glucagonlike peptide-1 (GLP-1) decreases beta cell apoptosis in a protein kinase B (PKB)-dependent fashion, and increases islet cell mass and function in vivo. In contrast, cytokines induce beta cell apoptosis, leading to decreased islet mass and type 1 diabetes. In the present study we used rat INS-1E beta cells and primary rat islet cells to examine the potential role of PKB as a mediator of the effect of GLP-1 on cytokine-induced apoptosis. Methods: Cell viability was determined by MTTassay, and apoptosis and necrosis by Hoechst 33342-propidium iodide staining. Immunoblot analysis was used to detect changes in protein expression, including active (phosphorylated) and total PKB, phosphorylated and total glycogen synthase kinase-3β, activated caspase-3 and inducible nitric oxide synthase. Reactive oxygen species were determined by 1,7-dichlorofluorescein (DCF) analysis, and mutant forms of PKB were introduced into cells using adenoviral vectors. Results: Incubation of INS-1E cells with cytokines (IL-1β, TNF-α and interferon-γ; 10-50 ng/ml) for 18 h significantly decreased cell viability (by 44%, p<0.001), cell proliferation (by 80%, p<0.001), and activation of PKB (by 67%, p<0.001). Pre-treatment with exendin-4 (10 −7 mol/l), a long-acting GLP-1 receptor agonist, partially protected the cells against cytokine-induced toxicity (p<0.01) in association with a reduction in cytokine-induced inhibition of PKB phosphorylation (p<0.05). Exendin-4 pre-treatment did not change cell proliferation. Cytokine treatment increased apoptosis (by 156%, p<0.05) and necrosis (from undetectable to 2.6% of cells). These increases were both reduced by pre-treatment with exendin-4 (p<0.05-0.01). Furthermore, cytokine-induced apoptosis and necrosis were significantly increased in cells infected with kinase-dead PKB (p<0.05), and the protective effect of exendin-4 on both parameters was fully abolished in these cells. Similar changes were observed in primary islet cells. In parallel with these changes, exendin-4 decreased the cytokine-induced activation of caspase-3 (by 46%, p<0.05), and decreased levels of inducible nitric oxide synthase (by 71%, p<0.05) and reactive oxygen species (by 27%, p< 0.05). Conclusions/interpretation: The results of our study indicate that GLP-1 plays a protective role against cytokineinduced apoptosis and necrosis in beta cells through a PKB-dependent signalling pathway.

show abstract

Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2

Cited by 189 publications

References 81 publications

Gastrointestinal regulation of food intake

Gastrointestinal regulation of food intake

The role of gut hormones in glucose homeostasis

Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B

Contact Info

Product

Resources

About