β-cell dysfunction is an early pathophysiological defect in type 2 diabetes mellitus. Conventional secretagogues, although effective in increasing insulin secretion, may be associated with undesirable side effects, including hypoglycemia, abnormalities in cardiovascular responses, and β-cell apoptosis. Glucagon-like peptide(GLP)-1 is an incretin hormone displaying glucose-dependent stimulation of insulin secretion, trophic effects on the pancreatic β-cells, and inhibitory effects on gastrointestinal motility, which has been shown to ameliorate hyperglycemia and reduce glycemic excursions. However, after parenteral administration native GLP-1 is rapidly degraded by plasma dipeptydil peptidase (DPP)-IV. Hence, degradation-resistant, long-acting GLP-1 receptor agonists have been proposed as novel agents for diabetes therapy. Alternatively, inhibitionof DPP-IV-mediated GLP-1 degradation represents another approach for exploiting GLP-1 beneficial effects on metabolic control. This review will summarize the biological effects of GLP-1, the general features of GLP-1 mimetics and DPP-IV inhibitors, and the promising results of recently published clinical trials testing these compounds for the treatment of type 2 diabetes. © 2006 Elsevier Ireland Ltd. All rights reserved.

GLP-1: a new approach for type 2 diabetes therapy

GIORGINO, Francesco;NATALICCHIO, ANNALISA;LAVIOLA, Luigi;LEONARDINI, ANNA
2006

Abstract

β-cell dysfunction is an early pathophysiological defect in type 2 diabetes mellitus. Conventional secretagogues, although effective in increasing insulin secretion, may be associated with undesirable side effects, including hypoglycemia, abnormalities in cardiovascular responses, and β-cell apoptosis. Glucagon-like peptide(GLP)-1 is an incretin hormone displaying glucose-dependent stimulation of insulin secretion, trophic effects on the pancreatic β-cells, and inhibitory effects on gastrointestinal motility, which has been shown to ameliorate hyperglycemia and reduce glycemic excursions. However, after parenteral administration native GLP-1 is rapidly degraded by plasma dipeptydil peptidase (DPP)-IV. Hence, degradation-resistant, long-acting GLP-1 receptor agonists have been proposed as novel agents for diabetes therapy. Alternatively, inhibitionof DPP-IV-mediated GLP-1 degradation represents another approach for exploiting GLP-1 beneficial effects on metabolic control. This review will summarize the biological effects of GLP-1, the general features of GLP-1 mimetics and DPP-IV inhibitors, and the promising results of recently published clinical trials testing these compounds for the treatment of type 2 diabetes. © 2006 Elsevier Ireland Ltd. All rights reserved.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/11870
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