Variation in characteristics of islets of Langerhans in insulin-resistant, diabetic and non-diabetic-rat strains.

Abstract

Assessment of the histopathological and plasma biochemical characteristics of diabetic and non-diabetic rat strains [Han and AP Wistar, lean and obese Zucker Fatty (ZF), and lean and obese Zucker Diabetic Fatty (ZDF) rats] was performed at 6 or 14 weeks of age. Wistar and lean ZF and ZDF rats showed no or minimal islet pathology or plasma biochemical alterations at both timepoints. Obese ZFs were euglycaemic at both timepoints and mildly and severely hyperinsulinaemic at 6 and 14 weeks respectively. Islet morphology was normal at 6 weeks but at 14 weeks, islet hyperplasia was present with a minority showing degenerative changes namely, beta-cell vacuolation, vascular congestion and haemorrhage with minimal mononuclear cell and T lymphocytic infiltration. Obese ZDFs were euglycaemic and moderately hyperinsulinaemic at 6 weeks and severely hyperglycaemic with minor hypoinsulinaemia at 14 weeks. Obese ZDFs at 6 weeks showed mainly normal islets with some displaying degeneration (ranging from beta-cell vacuolation alone to the features described above). At 14 weeks, islet degeneration was more severe and widespread: beta-cell death was present in numerous islets at low level. Islet beta-cell numbers were reduced or absent (with associated reduction in insulin immunostaining) within the islets that now consisted predominantly of fibroblasts, collagen and mononuclear cells. Fibroproliferation consisting of smooth muscle actin-alpha-positive tissue was associated with mononuclear cell infiltration. Some fibrous scars were visible indicative of lost islets. Islet degeneration in obese ZF and ZDF rats was not accompanied by a reduction in beta-cell proliferation or in compensatory proliferation of beta-cell neogenic clusters. In the light of recent reports of adaptive and inflammation-mediated degenerative changes in human non-insulin dependent diabetes mellitus (NIDDM) islets, the hypertrophy/hyperplasia of beta-cells and islet degeneration involving infiltration by monocyte/macrophages in obese ZF and obese ZDF rats respectively offers substantial potential for elucidation of the processes involved.