Defects in Insulin Secretion and Action in the Pathogenesis of Type 2 Diabetes Mellitus
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Type 2 diabetes mellitus (T2DM) is characterized by defects in insulin action and insulin secretion. Although insulin resistance manifests early during the prediabetic state, a failing β-cell function unable to overcome insulin resistance at target tissues determines the onset of T2DM. This review focuses on recent advances in the molecular mechanisms of insulin resistance and β-cell dysfunction. The role of mitochondrial dysfunction, impaired regulation of the enteroinsular axis, and endoplasmic reticulum stress are currently the subjects of intensive research. In addition, the adipose tissue has emerged as a major endocrine organ that secretes a growing list of adipocytokines with diverse central and peripheral metabolic effects. The role of a growing number of candidate genes and transcription factors regulating insulin action and secretion is also discussed.
KeywordsType 2 diabetes mellitus Insulin resistance Insulin secretory defects Mitochondrial dysfunction Free fatty acids Adipokines Incretins
Dr. Devjit Tripathy has received research support from Takeda Pharmaceuticals. No other potential conflicts of interest relevant to this article were reported.
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