Improved glucose regulation in type 2 diabetic patients with DPP-4 inhibitors: focus on alpha and beta cell function and lipid metabolism
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- 作者：Bo Ahrén ; James E. Foley
- 关键词：Dipeptidyl peptidase ; 4 inhibitors ; GIP ; GLP ; 1 ; Glucagon ; Insulin ; Review
- 刊名：Diabetologia
- 出版年：2016
- 出版时间：May 2016
- 年：2016
- 卷：59
- 期：5
- 页码：907-917
- 全文大小：674 KB
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James E. Foley (2)
1. Faculty of Medicine, Department of Clinical Sciences Lund, Lund University, B11 BMC, Sölvegatan 19, 22184, Lund, Sweden
2. World Wide Medical Affairs, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA - 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Internal Medicine
Metabolic Diseases
Human Physiology - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-0428
文摘
Inhibition of dipeptidyl peptidase-4 (DPP-4) is an established glucose-lowering strategy for the management of type 2 diabetes mellitus. DPP-4 inhibitors reduce both fasting and postprandial plasma glucose levels, resulting in reduced HbA1c with low risk for hypoglycaemia and weight gain. They act primarily by preventing inactivation of the incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, thereby prolonging the enhanced endogenous levels of these hormones after meal ingestion. This in turn causes islet and extrapancreatic effects, including increased glucose sensing in islet alpha and beta cells. These effects result in increased insulin secretion and decreased glucagon secretion being more effective in hyperglycaemic states and reduced insulin secretion and increased glucagon secretion being more effective during hypoglycaemia. Other secondary pharmacological actions of DPP-4 inhibitors include mobilisation and burning of fat during meals, decrease in fat extraction from the gut, reduction of fasting lipolysis and liver fat and increase in LDL particle size. These actions contribute to the clinical effects of DPP-4 inhibition, and the reduced demand for insulin could also lead to a durability benefit. This review summarises the current knowledge of the secondary pharmacological actions of DPP-4 inhibitors that lead to improved glucose regulation in patients with type 2 diabetes, focusing on alpha and beta cell function and lipid metabolism.