Expression of somatostatin receptor subtypes 1-5 in pancreatic islets of normoglycaemic and diabetic NOD mice.

Objective: Somatostatin acts on five specific receptors (sst1-5) to elicit different biological functions. The non-obese diabetic (NOD) mouse is an experimental model of type I diabetes. The aim of this study was to investigate whether the islet expression of sst1-5 is affected during the development of diabetes in NOD mice, with insulitis accompanied by spontaneous hyperglycaemia. Methods: By immunostaining for sst1-5 the expression and co-expression together with the four major islet hormones in pancreatic islets were investigated in female and male NOD mice at different stages of disease. The NOD related non-diabetic ICR mouse was also examined. Results: The islet cells of diabetic NOD mice showed an increased islet cell expression of sst2-5 compared with normoglycaemic female NOD mice. This correlated to increasing age and extent of insulitis. Major findings from the co-expression investigations were that sst2 was expressed in a majority of R-cells in the normoglycaemic NOD mice, but absent in the beta-cells in the diabetic NOD mice. A majority of the a-cells expressed sst2 and 5 in normoglycaemic and diabetic NOD mice. About 60% of delta-cells showed co-expression of sst4 and 5 in both normoglycaemic and diabetic NOD mice. 60% of pancreatic polypeptide (PP)-cells expressed sst4 in both groups. Insulitis was found to be accompanied by a down-regulation of sst in normoglycaemic animals. Conclusions: The difference in sst expression in the islets cells of diabetic mice may suggest either a contributing factor in the process leading to diabetes, or a defence response against ongoing beta-cell destruction.