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

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

SUBMITTER: He W 

PROVIDER: S-EPMC5807311 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature