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- Title
β-Cell compensation concomitant with adaptive endoplasmic reticulum stress and β-cell neogenesis in a diet-induced type 2 diabetes model.
- Authors
Huang, Hui; Yang, Kaiyuan; Wang, Rennian; Han, Woo Hyun; Kuny, Sharee; Zelmanovitz, Paula Horn; Sauvé, Yves; Chan, Catherine B.
- Abstract
Insulin-secreting pancreatic β-cells adapt to obesity-related insulin resistance via increases in insulin secretion and β-cell mass. Failed β-cell compensation predicts the onset of type 2 diabetes (T2D). However, the mechanisms of β-cell compensation are not fully understood. Our previous study reported changes in β-cell mass during the progression of T2D in the Nile rat (NR; Arvicanthis niloticus) fed standard chow. In the present study, we measured other β-cell adaptive responses, including glucose metabolism and β-cell insulin secretion in NRs at different ages, thus characterizing NR at 2 months as a model of β-cell compensation followed by decompensation at 6 months. We observed increased proinsulin secretion in the transition from compensation to decompensation, which is indicative of impaired insulin processing. Subsequently, we compared adaptive unfolded protein response in β-cells and demonstrated a positive role of endoplasmic reticulum (ER) chaperones in insulin secretion. In addition, the incidence of insulin-positive neogenic but not proliferative cells increased during the compensation phase, suggesting nonproliferative β-cell growth as a mechanism of β-cell mass adaptation. In contrast, decreased neogenesis and β-cell dedifferentiation were observed in β-cell dysfunction. Furthermore, the progression of T2D and pathophysiological changes of β-cells were prevented by increasing fibre content of the diet. Novelty Our study characterized a novel model for β-cell compensation with adaptive responses in cell function and mass. The temporal association of adaptive ER chaperones with blood insulin and glucose suggests upregulated chaperone capacity as an adaptive mechanism. β-Cell neogenesis but not proliferation contributes to β-cell mass adaptation.
- Subjects
TYPE 2 diabetes prevention; PREVENTION of disease progression; PHYSIOLOGICAL adaptation; ANIMAL experimentation; BLOOD sugar; DIET; ENDOPLASMIC reticulum; INSULIN; ISLANDS of Langerhans; MOLECULAR chaperones; TYPE 2 diabetes; RATS; PHYSIOLOGICAL stress
- Publication
Applied Physiology, Nutrition & Metabolism, 2019, Vol 44, Issue 12, p1355
- ISSN
1715-5312
- Publication type
Article
- DOI
10.1139/apnm-2019-0144