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Ageing potentiates diet-induced glucose intolerance, β-cell failure and tissue inflammation through TLR4.

Ageing potentiates diet-induced glucose intolerance, β-cell failure and tissue inflammation through TLR4.
Author Information (click to view)

He W, Yuan T, Choezom D, Hunkler H, Annamalai K, Lupse B, Maedler K,


He W, Yuan T, Choezom D, Hunkler H, Annamalai K, Lupse B, Maedler K, (click to view)

He W, Yuan T, Choezom D, Hunkler H, Annamalai K, Lupse B, Maedler K,

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Scientific reports 2018 02 098(1) 2767 doi 10.1038/s41598-018-20909-w
Abstract

Ageing and obesity are two major risk factors for the development of type 2 diabetes (T2D). A chronic, low-grade, sterile inflammation contributes to insulin resistance and β-cell failure. Toll-like receptor-4 (TLR4) is a major pro-inflammatory pathway; its ligands as well as downstream signals are increased systemically in patients with T2D and at-risk individuals. In the present study we investigated the combined effects of high fat/high sucrose diet (HFD) feeding, ageing and TLR4-deficiency on tissue inflammation, insulin resistance and β-cell failure. In young mice, a short-term HFD resulted in a mildly impaired glucose tolerance and reduced insulin secretion, together with a β-cell mass compensation. In older mice, HFD further deteriorated insulin secretion and induced a significantly impaired glucose tolerance and augmented tissue inflammation in adipose, liver and pancreatic islets, all of which was attenuated by TLR4 deficiency. Our results show that ageing exacerbates HFD-induced impairment of glucose homeostasis and pancreatic β-cell function and survival, and deteriorates HFD-induced induction of mRNA expression of inflammatory cytokines and pro-inflammatory macrophage markers. TLR4-deficiency protects against these combined deleterious effects of a high fat diet and ageing through a reduced expression of inflammatory products in both insulin sensitive tissues and pancreatic islets.

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