Pathology of the Nile rat developing type 2 diabetes

Abstract

The Nile rat (NR) develops metabolic syndrome and type 2 diabetes (T2DM) in a manner similar to humans (NutrMetab 7: 29, 2010). To characterize the pathology of developing T2DM, relevant organs (pancreas, liver, kidney) were examined histopathologically. Immunohistochemical analyses of the pancreatic β cells were performed, as well. Fatty infiltration of the pancreas and hepatic steatosis were the most prevalent early lesions. Rats with advanced T2DM revealed a loss of pancreatic islet cells and insulin immunoreactivity. Hepatomegaly and discoloration were present macroscopically. This was confirmed as mid‐zonal to diffuse steatosis with microscopic foci of steatitis, accompanied by increased triglycerides and cholesterol esters. Hepatic steatosis was correlated with advancing T2DM, but was more pronounced in rats fed a modCHO/modFat diet compared to hiCHO/loFat rats, where clinical T2DM developed most rapidly. Selected chow‐fed diabetic rats >;1y of age with chronic hyperinsulinemia were found to have nodular hepatomas, not unlike non‐alcoholic steatohepatosis in humans. Histopathology of the kidney revealed the 4 stages of diabetic nephropathy described in humans, including early thickening of the glomerular basement membranes followed by thickening and increased interstitial fibrosis with end‐stage glomerular sclerosis.Funding source: Foster Biomed Res Lab and the Malaysian Palm Oil Board.