Beta-cell failure in type 2 diabetes mellitus.
Diabetes mellitus has been defined as a "group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both" and encompasses a wide range of heterogeneous conditions. Common type 2 diabetes mellitus (T2DM) results from a combination of genetic and acquired factors. However, lifestyle factors, particularly overeating and physical inactivity, are the major clinical determinants of T2DM. Insulin resistance is a common feature of T2DM, but it is unlikely to cause T2DM unless progressive loss of beta-cell function develops. Significant reduction in beta-cell function is already present at the time of T2DM diagnosis, and it continuously declines irrespective of treatment. As such, the progressive loss of beta-cell function dictates the rate of worsened glycemic control. Development of progressive deterioration accelerates via gluco- and lipotoxicity, loss of beta-cell function, and shrinkage of beta-cell mass. Understanding the causes for beta-cell failure is therefore of capital importance to develop new and more effective therapeutic strategies.
Lencioni
Cristina
C
Department of Endocrinology and Metabolism, Section of Diabetes and Metabolic Diseases, University of Pisa, Ospedale Cisanello, Via Paradisa, 2, 56124 Pisa, Italy.
Lupi
Roberto
R
Del Prato
Stefano
S
D000682:Amyloid / Q000009:adverse effects; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000473:pathology*; D005947:Glucose / Q000009:adverse effects; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008055:Lipids / Q000009:adverse effects
D000682:Amyloid; D008055:Lipids; D005947:Glucose