Role of FoxO1 in regulating autophagy in type 2 diabetes mellitus (Review)

Abstract

Type 2 diabetes mellitus (T2DM) is a major chronic disease that is characterized by pancreatic β-cell dysfunction and insulin resistance. Autophagy is a highly conserved intracellular recycling pathway and is involved in regulating intracellular homeostasis. Transcription factor Forkhead box O1 (FoxO1) also regulates fundamental cellular processes, including cell differentiation, metabolism and apoptosis, and proliferation to cellular stress. Increasing evidence suggest that autophagy and FoxO1 are involved in the pathogenesis of T2DM, including β-cell viability, apoptosis, insulin secretion and peripheral insulin resistance. Recent studies have demonstrated that FoxO1 improves insulin resistance by regulating target tissue autophagy. The present review summarizes current literature on the role of autophagy and FoxO1 in T2DM. The participation of FoxO1 in the development and occurrence of T2DM via autophagy is also discussed.

Keywords: FoxO1; T2DM; autophagy; insulin resistance; pancreatic β-cell.

Figure 1

FoxO1 promotes insulin resistance by upregulating PEPCK and G6Pase expression. FoxO1 inhibits insulin resistance by downregulating fasting triglyceride and cholesterol levels, and suppressing Fasn/Hmger and tribble 3 expression, while upregulating adiponectin and UCP-1 expression. FoxO1, Forkhead box O1; PEPCK, phosphoenolpyruvate carboxykinase; G6Pase, glucose-6-phosphatase; UCP1, uncoupling protein 1.