Five stages of progressive β-cell dysfunction in the laboratory Nile rat model of type 2 diabetes. Issue 3 (June 2016)

• Record Type: Journal Article
• Authors: Yang, Kaiyuan; Gotzmann, Jonathan; Kuny, Sharee; Huang, Hui; Sauvé, Yves; Chan, Catherine B
• Is Part Of: Journal of endocrinology. Volume 229:Issue 3(2016)
• Page Start: 343
• Page End: 356
• Publication Date: 2016-06
• Subjects: insulin resistance -- type 2 diabetes -- animal model -- insulin processing -- endoplasmic reticulum stress; Endocrinology -- Periodicals; 616.4005
• DOI: 10.1530/JOE-15-0517
• Languages: English
• ISSNs: 0022-0795

Abstract

Abstract : We compared the evolution of insulin resistance, hyperglycemia, and pancreatic β-cell dysfunction in the Nile rat ( Arvicanthis niloticus ), a diurnal rodent model of spontaneous type 2 diabetes (T2D), when maintained on regular laboratory chow versus a high-fiber diet. Chow-fed Nile rats already displayed symptoms characteristic of insulin resistance at 2 months (increased fat/lean mass ratio and hyperinsulinemia). Hyperglycemia was first detected at 6 months, with increased incidence at 12 months. By this age, pancreatic islet structure was disrupted (increased α-cell area), insulin secretion was impaired (reduced insulin secretion and content) in isolated islets, insulin processing was compromised (accumulation of proinsulin and C-peptide inside islets), and endoplasmic reticulum (ER) chaperone protein ERp44 was upregulated in insulin-producing β-cells. By contrast, high-fiber-fed Nile rats had normoglycemia with compensatory increase in β-cell mass resulting in maintained pancreatic function. Fasting glucose levels were predicted by the α/β-cell ratios. Our results show that Nile rats fed chow recapitulate the five stages of progression of T2D as occurs in human disease, including insulin-resistant hyperglycemia and pancreatic islet β-cell dysfunction associated with ER stress. Modification of diet alone permits long-term β-cell compensation and prevents T2D.