Pancreatic islet dysfunction in type 2 diabetes mellitus

Abstract

Islet dysfunction is a hallmark of type 2 diabetes mellitus (T2DM). Compelling evidence suggests that accumulation of islet amyloid in the islets of Langerhans significantly contribute to β-cell dysfunction and diabetes. Emerging evidence implicates a role for cystic fibrosis transmembrane-conductance regulator in the regulation of insulin secretion from pancreatic islets. Impaired first-phase insulin responses and glucose homeostasis have also been reported in cystic fibrosis patients. The transforming growth factor-β protein superfamily is central regulators of pancreatic cell function, and has a key role in pancreas development and pancreatic disease, including diabetes and islet dysfunction. It is also becoming clear that islet inflammation plays a key role in the development of islet dysfunction. Inflammatory changes, including accumulation of macrophages, have been documented in type 2 diabetic islets. Islet dysfunction leads to hyperglycemia and ultimately the development of diabetes. In this review, we describe these risk factors and their associations with islet dysfunction.

KEYWORDS:

• Islet dysfunction
• islet amyloid polypeptide
• cystic fibrosis transmembrane conductance regulator
• transforming growth factor-β
• islet inflammation
• type 2 diabetes mellitus

Acknowledgements

This work was supported by the Ningbo Science and Technology Huimin Program (2017C50040); the Ningbo Science and Technology Innovation Team Program (2014B82002); the Fang Runhua Fund of Hong Kong and K. C. Wong Magna Fund in Ningbo University.

Disclosure statement

The authors declare no conflict of interest.