Glucagon-like Peptide 1 (GLP-1) in the Treatment of Diabetes

M. A. Nauck

doi:10.1055/s-2004-826175

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2004; 36(11/12): 852-858
DOI: 10.1055/s-2004-826175

Review

Glucagon-like Peptide 1 (GLP-1) in the Treatment of Diabetes

M. A. Nauck¹

¹ Diabeteszentrum Bad Lauterberg, Germany

Abstract

Glucagon-like peptide 1 (GLP-1) was discovered as an incretin (insulinotropic gut) hormone. Biological actions of GLP-1 in healthy and type 2 diabetic subjects include (a) stimulation of insulin secretion in a glucose-dependent manner, (b) suppression of glucagon, (c) reduction in appetite and food intake, (d) deceleration of gastric emptying. In animal experiments, in addition, (e) stimulation of β-cell neogenesis, growth and differentiation in animal and tissue culture experiments, and (f) in vitro inhibition of β-cell apoptosis induced by different agents have been observed. Since the incretin effect - the higher insulin secretory response to oral as compared to intravenous glucose loads - is reduced in patients with Type 2 diabetes, GLP-1 has been used to pharmacologically replace incretin. Intravenous GLP-1 can normalise, and subcutaneous GLP-1 can significantly lower plasma glucose in the majority of patients with Type 2 diabetes. The magnitude of this effect does not greatly depend on patient characteristics such as age, sex, obesity, or baseline insulin and glucagon, with minor influences of previous antidiabetic therapy and actual metabolic control. GLP-1 itself, however, is inactivated rapidly in vivo by the protease DPP IV and can only be used for short-term metabolic control, such as in intensive care units (potentially useful in patients with acute myocardial infarction, coronary surgery, cerebrovascular events, septicaemia, during the perioperative period and while on parenteral nutrition). For more long-term metabolic control, incretin mimetics (agonists at the GLP-1 receptor) with more favourable pharmacokinetic profiles should be used.

Key words

Glucagon-like peptide-1 - Incretin - Incretin mimetic - Type 2 diabetes - Insulin - Glucagon - β-cell - Obesity - Gastric emptying

Full Text

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Prof. Dr. med. M. A. Nauck

Diabeteszentrum Bad Lauterberg

Kirchberg 21 · 37431 Bad Lauterberg im Harz · Germany

Phone: +49 (524) 81-218

Fax: +49 (524) 81-398

Email: M.Nauck@diabeteszentrum.de