In type 2 diabetes induced by cigarette smoking, activation of p38 MAPK is involved in pancreatic β-cell apoptosis.

Abstract

Type 2 diabetes (T2D) is a chronic disease caused by pancreatic β-cell dysfunction and insulin resistance. Exposure to smoke is a risk factor for diabetes; however, its mechanisms are unclear. In an epidemiological study, we determined the relationship between cigarette smoking and β-cell function. T2D patients had a history of heavier smoking than people without T2D, and heavy smokers had more abnormal glucose metabolism. For various smoking populations, there was a dose-effect relationship between decreases of homeostatic model assessment (HOMA)-β levels or the increases of HOMA-insulin resistance (IR) levels and amount of smoking (pack-years), which indicated that smoking induced β-cell dysfunction. For MIN6 cells, cigarette smoke extract (CSE) decreased insulin secretion and content; enhanced apoptosis, as illustrated by decreases of BCL-2 levels, increases of BAX and cleaved caspase-3 levels, and an increased apoptotic index; and activated the p38 MAPK pathway. For MIN6 cells, inhibition of p-p38 MAPK by SB203580 prevented enhanced apoptosis and the dysfunction of insulin secretion induced by CSE. In sum, activation of p38 MAPK is involved in the apoptosis of pancreatic β-cells induced by cigarette smoking, which is a possible mechanism for induction of T2D by cigarette smoke.