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

Abstract

The dysregulation of the β-cell functional mass, which is a reduction in the number of β-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 β-cell loss and dysfunction and a risk factor for T2D. The natural history of β-cell failure in obesity-induced T2D can be divided into three steps: (1) β-cell compensatory hyperplasia and insulin hypersecretion, (2) insulin secretory dysfunction, and (3) loss of β-cell mass. Adipose tissue (AT) secretes many hormones/cytokines (adipokines) and fatty acids that can directly influence β-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 β-cells could drive the maintenance of the β-cell integrity under physiological conditions and contribute to the reduction in the β-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 β-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 β-cell functional mass.

Keywords: adipokines; adipose tissue; cross-talk; obesity; pancreatic β-cells; type 2 diabetes.

Figure 1

Timeline of the possible alterations in the adipokines secretion pattern in the transition from obesity to T2D that reflects the progressive deterioration of β-cell functional mass. ↑, increased levels; ↓, decreased levels. AGT, angiotensinogen; AngII, angiotensinogen II; DPP-4, dipeptidyl peptidase-4; FABP4, fatty acid-binding protein specific for adipocytes; FFAs, free fatty acids; IL-6, interleukin-6; MIP-1α, macrophage inflammatory protein-1α; RANTES, regulated upon activation normal T cells, expressed and secreted; TIMP-1, tissue inhibitor of metalloproteinases-1; TNF-α, tumour necrosis factor-α.