Immunohistochemical, Ultrastructural, and Hormonal Studies on the Endocrine Pancreas of Voles (Microtus arvalis) with Monosodium Aspartate-induced Diabetes

Abstract

A single subcutaneous administration of monosodium aspartate (MSA) to 30 neonatal voles, Microtus arvalis Pallas, induced a diabetes mellitus in 50% of the treated animals in early adulthood. The voles (18 males and 12 females) were weaned at 3 weeks of age and fed pellets for Herbivora and cubed hay. Diabetic voles with glycosuria (nine males and six females) were classified into two groups according to the duration and grade of glycosuria. One group had slight diabetes with glycosuria (+: 0.1%) for 1 week and the other severe diabetes with marked glycosuria (+++: ≧0.5%) for over 4 weeks. Pancreatic islets of diabetic voles ( n = 7) were examined immunohistochemically, light microscopically, and electron microscopically. Blood glucose concentration and tissue content of insulin, glucagon, and somatostatin were also measured. Slightly diabetic voles ( n = 3) had enlarged islets, that, viewed by light microscopy, were characterized by hypertrophy and hyperplasia of β cells with moderate degranulation. No changes were observed in the peripherally located α and β cells; the voles were moderately hyperglycemic, and they had decreased pancreatic insulin content. Severely diabetic voles ( n = 4) that had marked hyperglycemia and almost complete loss of insulin content showed marked vacuolation and degranulation of β cells. In addition, altered distribution of α and β cells from the periphery of the islets to their interior was noted. Ultrastructural examination revealed features compatible with those of hyperfunction of β cells in the slightly diabetic voles and marked degeneration of β cells with glycogen accumulation in the severely diabetic voles. In contrast, α and β cells retained their normal morphologic traits, even in the severely diabetic voles.