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.

Non-altered incretin secretion in women with impaired fasting plasma glucose in the early stage of pregnancy: a case control study

“…Although BMI did not correlate with both fasting and postprandial incretin production and women with impaired fasting glucose did not show a significant increase in markers of insulin resistance (HOMA-IR, QUICKI), they had reduced beta-cell function as measured by HOMA-β. Obesity can impair glycemic compensation not only through insulin resistance but also through disruption of beta-cell function due to adverse secretion of adipokines [ 28 , 29 ]. Unbalanced adipokine (low adiponectin, high leptin) levels were detected even in overweight women with early-onset GDM [ 30 ].…”

Association between Intrapancreatic Fat Deposition and Lower High-Density Lipoprotein Cholesterol in Individuals with Newly Diagnosed T2DM

“…This irrelevance could be partly explained by methodological (such as insufficient enrollment and inevitable limitation of the HOMA model) and pathophysiological factors. Firstly, the pancreatic β cells had a strong compensatory capacity to tolerate the adverse effects of ectopic fat deposition [ 21 ], and individuals with newly diagnosed T2DM might remain a certain extent of this adapted ability. Secondly, the simultaneous activation of several deleterious cascades might further accelerate β -cell dysfunction, including oxidative stress, chronic inflammation, hypoperfusion of islets, and β -cell apoptosis, and thus the deterioration of β -cell function developed at a rate disproportionate to pancreatic fat deposition [ 22 ].…”

Adipose Tissue Dysfunction and Obesity-Related Male Hypogonadism

“…Obesity is also known to alter the release of adipocytokines from AT, resulting in important health consequences [ 24 , 25 , 26 ]. For instance, the increased secretion of leptin by expanded AT is known to impair central leptin signaling and to participate in the development of metabolic alterations and HPT dysfunction [ 27 , 28 , 29 ].…”