Gut peptides and type 2 diabetes mellitus treatment

被引：107

作者：

Bo Ahrén

机构：

[1] Department of Medicine, Lund University

来源：

Current Diabetes Reports | 2003年 / 3卷 / 5期

关键词：

Gastric Emptying; Gastric Inhibitory Polypeptide; Gastric Inhibitory Polypeptide; Stimulate Insulin Secretion; Meal Ingestion;

D O I：

10.1007/s11892-003-0079-9

中图分类号：

学科分类号：

摘要：

The gut expresses peptide hormones in endocrine cells and neuropeptides in autonomic nerves. Several of these peptides have the ability to stimulate insulin secretion. Gut hormones that are released after meal ingestion and stimulate insulin secretion postprandially are called incretins. In humans, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the most important incretins. The potential use of these insulinotropic gut peptides for the treatment of diabetes has been considered. This has been most successful for GLP-1, which exerts antidiabetogenic properties in subjects with type 2 diabetes by stimulating insulin secretion, increasing β-cell mass, inhibiting glucagon secretion, delaying gastric emptying, and inducing satiety. However, GLP-1 is rapidly degraded by the enzyme dipeptidyl peptidase IV (DPPIV), making it unattractive as a therapeutic agent because of a very short half-life. Successful strategies to overcome this difficulty are the use of DPPIV-resistant GLP-1 receptor agonists, such as NN2211 or exendin-4, and the use of inhibitors of DPPIV, such as NVPDPP728 and P32/98. These two approaches are explored in clinical investigations. Copyright © 2003 by Current Science Inc.

引用

页码：365 / 372

页数：7

共 50 条

[21] Buteay J., Roduit R., Susini S., Prentki M., Glucagon-like peptide-1 promotes DNA synthesis, activates phosphatidylinositol 3-kinase and increases transcription factor pancreatic and duodenal homeobox gene 1 (PDX-1) DNA binding activity in beta (INS-1)-cells, Diabetologia, 42, pp. 856-864, (1999)
[22] Drucker D.J., Glucagon-like peptides: Regulators of cell proliferation, differentiation, and apoptosis, Mol. Endocrinol., 17, pp. 161-171, (2003)
[23] Larsson H., Holst J.J., Ahren B., Glucagon-like peptide-1 reduces hepatic glucose production indirectly through insulin and glucagon in humans, Acta Physiol. Scand., 160, pp. 413-422, (1997)
[24] Nauck M.A., Niedereichholz U., Ettler R., Et al., Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans, Am. J. Physiol., 273, (1997)
[25] Verdich C., Flint A., Gutzwiller J.P., Et al., A meta-analysis of the effect of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake in humans, J. Clin. Endocrinol. Metab., 86, pp. 4382-4389, (2001)
[26] Ahren B., Larsson H., Holst J.J., Effects of glucagon-like peptide-1 on islet function and insulin sensitivity in noninsulin-dependent diabetes mellitus, J. Clin. Endocrinol. Metab., 82, pp. 473-478, (1997)
[27] Egan J.M., Meneilly G.S., Habener J.F., Elahi D., Glucagon-like peptide-1 augments insulin-mediated glucose uptake in the obese state, J. Cin. Endocrinol. Metab., 87, pp. 3673-3768, (2002)
[28] Gutniak M., Orskov C., Holst J., Et al., Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects and patients with diabetes mellitus, N. Engl. J. Med., 326, pp. 1316-1322, (1992)
[29] Juntti-Berggren L., Pigon J., Karpe F., Et al., The antidiabetogenic effect of GLP-1 is maintained during a 7-day treatment period and improves diabetic dyslipoproteinemia in NIDDM patients, Diabetes Care, 19, pp. 1200-1206, (1996)
[30] Toft-Nielsen M.B., Madsbad S., Holst J.J., Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients, Diabetes Care, 22, pp. 1137-1143, (1999)

← 1 2 3 4 5 →