Adipose Tissue Secretion Pattern Influences β-Cell Wellness in the Transition from Obesity to Type 2 Diabetes

The dysregulation of the beta-cell functional mass, which is a reduction in the number of beta-cells and their ability to secure adequate insulin secretion, represents a key mechanistic factor leading to the onset of type 2 diabetes (T2D). Obesity is recognised as a leading cause of beta-cell loss and dysfunction and a risk factor for T2D. The natural history of beta-cell failure in obesity-induced T2D can be divided into three steps: (1) beta-cell compensatory hyperplasia and insulin hypersecretion, (2) insulin secretory dysfunction, and (3) loss of beta-cell mass. Adipose tissue (AT) secretes many hormones/cytokines (adipokines) and fatty acids that can directly influence beta-cell function and viability. As this secretory pattern is altered in obese and diabetic patients, it is expected that the cross-talk between AT and pancreatic beta-cells could drive the maintenance of the beta-cell integrity under physiological conditions and contribute to the reduction in the beta-cell functional mass in a dysmetabolic state. In the current review, we summarise the evidence of the ability of the AT secretome to influence each step of beta-cell failure, and attempt to draw a timeline of the alterations in the adipokine secretion pattern in the transition from obesity to T2D that reflects the progressive deterioration of the beta-cell functional mass.

Automated summary

This review summarises the impact of obesity on beta-cell dysfunction, focusing on the natural history of beta-cell failure in obesity-induced T2D and the influence of AT secretome on beta-cells.