Bao-Sheng Yu1, An-Ru Wang. 1. Department of Pediatric Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China. drbsyu@yahoo.com.cn
Abstract
BACKGROUND: Incidence of type 2 diabetes mellitus (T2DM) has increased in young people in recent years and new therapies are required for its effective treatment. Glucagon-like peptide 1 (GLP-1) is a potent blood glucose-lowering hormone produced in the L cells of the intestine. It may be potentially effective in the treatment of hyperglycemia in patients with T2DM. DATA SOURCES: PubMed database were searched with the terms "GLP-1", "incretins" and "diabetes". RESULTS: GLP-1 is a product of the glucagon gene, and its secretion is controlled by both neural and endocrine signals. GLP-1 lowers plasma glucose by stimulating insulin and suppressing secretion of glucagons, thus inhibiting gastric emptying and reducing appetite. GLP-1 exerts these actions by the engagement of structurally distinct G-protein-coupled receptors (GPCRs). In patients with T2DM, GLP-1 increases insulin secretion and normalizes both fasting and postprandial blood glucose when given as a continuous intravenous infusion. However, the native hormone is unsuitable as a drug because it is broken down rapidly by dipeptidyl peptidase IV (DPP-4) and cleared by the kidneys. Fortunately, many GLP-1 agonists or analogues and DPP-4 inhibitors have been found or developed, such as exendin-4, exenatide, liraglutide, CJC1131, vidaliptin and P32/98. Clinical trials have shown their therapeutic functions in T2DM with little adverse reaction. CONCLUSION: A GLP-1 based therapy will be safe and effective for the treatment of T2DM.
BACKGROUND: Incidence of type 2 diabetes mellitus (T2DM) has increased in young people in recent years and new therapies are required for its effective treatment. Glucagon-like peptide 1 (GLP-1) is a potent blood glucose-lowering hormone produced in the L cells of the intestine. It may be potentially effective in the treatment of hyperglycemia in patients with T2DM. DATA SOURCES: PubMed database were searched with the terms "GLP-1", "incretins" and "diabetes". RESULTS:GLP-1 is a product of the glucagon gene, and its secretion is controlled by both neural and endocrine signals. GLP-1 lowers plasma glucose by stimulating insulin and suppressing secretion of glucagons, thus inhibiting gastric emptying and reducing appetite. GLP-1 exerts these actions by the engagement of structurally distinct G-protein-coupled receptors (GPCRs). In patients with T2DM, GLP-1increases insulin secretion and normalizes both fasting and postprandial blood glucose when given as a continuous intravenous infusion. However, the native hormone is unsuitable as a drug because it is broken down rapidly by dipeptidyl peptidase IV (DPP-4) and cleared by the kidneys. Fortunately, many GLP-1 agonists or analogues and DPP-4 inhibitors have been found or developed, such as exendin-4, exenatide, liraglutide, CJC1131, vidaliptin and P32/98. Clinical trials have shown their therapeutic functions in T2DM with little adverse reaction. CONCLUSION: A GLP-1 based therapy will be safe and effective for the treatment of T2DM.
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