Analysis of pancreatic islet cells and hormone content in the spontaneously diabetic KKAy mouse by morphometry, immunocytochemistry and radioimmunoassay

Abstract

The splenic pancreas of 165 day old diabetic KKAy and age-matched nondiabetic C57BL/6 mice was examined by morphometry and immunocytochemistry at the light microscopic level and by radioimmunoassay to evaluate the morphology, surface area, endocrine cell composition and hormone content of the pancreatic islets. The insulin cells of the diabetic mice were severely degranulated and many of the glucagon, somatostatin and pancreatic polypeptide cells were displaced from the mantle to the core of the islet tissue where the non-insulin cells appeared to lose their continuity. The topography of some of the islets of KKAy mice was further deranged by acinar cells among the endocrine tissue. Morphometric analysis revealed that the surface area of the islets of KKAy mice was significantly expanded in comparison with that of C57BL/6 mice. The volume and numerical percents of the insulin cells were significantly increased whereas those of the glucagon and somatostatin cells were decreased in the KKAy mice. Since only the mean absolute number of insulin cells was elevated in the diabetic mice, the alteration in the relative proportions of the non-insulin cells and hypertrophy of the islets seemed to be a manifestation of insulin cell hyperplasia. Pancreatic insulin and somatostatin contents were markedly diminished in the islets of KKAy compared with those of C57BL/6 mice. These results demonstrate that the microscopic anatomy, endocrine cell populations and hormone content of the pancreatic islets are deranged in the KKAy mouse with severe hyperinsulinemia and hyperglycemia.

Glomerulopathy in the KK.Cg-Ay/J Mouse Reflects the Pathology of Diabetic Nephropathy

“…This model exhibits marked obesity, glucose intolerance, severe insulin resistance, dyslipidemia, and hypertension [16–18]. KK- A y mice also develop renal disease characterized by moderate albuminuria with mild glomerular pathology and podocyte loss [19–21].…”

Glucose-induced changes of multiple mouse islet proteins analysed by two-dimensional gel electrophoresis and mass spectrometry

“…Although such measures improve the glycaemic control, the mechanisms behind the deranged GSIS are still to a large extent unknown. In this context the observation that islets from ob/ob and KKA y mice, which are animal models of type 2 diabetes mellitus [4,5], and from C57BL/6J control mice demonstrate improved GSIS after exposure to elevated glucose concentrations [6][7][8] is of interest. Indeed, such beneficial effects on GSIS have been correlated to changes in expression of individual islet proteins such as glucose transporter 2, glucokinase and uncoupling protein 2 [9][10][11].…”

Testicular Mineralization in KK-A^y Mice Treated with an Oxovanadium Complex

“…If VO 2+ complexes show reproductive toxicity, it would be fatal in humans, because many people take various vanadium (V 4+ and V 5+ ) salts by gavage as supplements. In this study, we performed a histological assessment of testicular toxicity after repeated administration of VO(opt) 2 in KK-A y mice, a mouse model of type 2 diabetes mellitus (DM) 11 , 12 , 13 , 14 .…”