Rosiglitazone protects against beta cell destruction in ZDF (Type 2) diabetic rats

The progression of type 2 diabetes involves insulin resistance, impairment in insulin secretion, and eventual loss of β‐cell mass. Current therapies largely address insulin sensitivity and secretion but it is also important that therapies be found which protect against β‐cell loss. Finegood et al (2000) have reported that rosiglitazone (RSG) treatment largely prevents loss of β‐cell mass. We have confirmed this observation and present new information on islet morphology during this process. Examination of pancreas sections from 6 week‐old ZDF fa/fa rats, by means of double immunofluorescence staining for insulin and glucagon, revealed the normal oval morphology of islets with a mantle of α‐cells at the periphery and β‐cells in the central region. Six weeks of treatment with RSG (10 μmol/kg BW/day) maintained this structure whereas, in untreated rats, the islets had lost their normal architecture. After another 6 weeks, atrophy of the islets, fibrosis and loss of insulin‐positive cells was observed in the untreated rats whereas in the treated group, the islets were larger with numerous insulin‐positive cells. However, at this time point, islets from both groups showed diffusion into exocrine tissue and loss of the α‐cell mantle. The appearance of signs of endoplasmic reticulum stress during the loss of islet integrity was also protected against by RSG. (Supported by CIHR and Canadian Diabetes Association).