Five stages of progressive β-cell dysfunction in the laboratory Nile rat model of type 2 diabetes

    1. Catherine B Chan1,2
    1. 1Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
    2. 2Department of Physiology, University of Alberta, Edmonton, Alberta, Canada
    3. 3Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, Alberta, Canada
    1. Correspondence should be addressed to Y Sauvé; Email: ysauve{at}


    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.

    • Received 1 April 2016
    • Accepted 11 April 2016
    • Made available online as an Accepted Preprint 1 June 2016
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