Ciglitazone, a new hypoglycaemic agent. 4. Effect on pancreatic islets of C57BL/6J-ob/ob and C57BL/KsJ-db/db mice

Abstract

Pancreases of treated and control male C57BL/6J-ob/ob and C57BL/KsJ-db/db mice were evaluated by qualitative and morphometric microscopic techniques to determine the effects of chronic ciglitazone treatment on the morphology of beta cells and surface area and number of pancreatic islets. The beta cells of treated ob/ob and db/db mice displayed moderate to heavy granulation whereas most beta cells of untreated obese and diabetic mice were extensively degranulated. Although moderate proliferation of the rough endoplasmic reticulum and Golgi apparatus was evident in some beta cells of treated db/db mice, both groups of treated ob/ob and db/db mice displayed an improved pattern of insulin synthesis and storage. In contrast, the beta cells of untreated ob/ob and db/db mice were in a severe state of stress which was indicated by extensive hypertrophy of the rough endoplasmic reticulum, Golgi apparatus and mitochondria. Some beta cells of untreated db/db mice also displayed lysosome aggregates indicative of early stages of necrosis. Morphometric analysis revealed that the surface area of islets of treated ob/ob mice was significantly smaller in comparison with that of untreated ob/ob mice. Since the surface area of islets of treated C57BL/6J-+/? mice (lean littermates of ob/ob mice) was less than that of treated ob/ob mice, the progression of islet hypertrophy in the obese mice was probably arrested or attenuated but not to the level of the treated +/? mice. The number of pancreatic islets was significantly greater in treated than in untreated db/db mice. A majority of the islets of untreated db/db mice were atrophic and consisted of acinar and endocrine cells whereas most of the islets of treated db/db mice appeared to be intact and unremarkable. The results of this study suggest that ciglitazone is an effective hypoglycaemic agent which may directly or indirectly promote beta-cell regranulation and an improved pattern of insulin synthesis and storage in ob/ob and db/db mice. However, in treated db/db mice, there still was some evidence of stress in the beta cells. Overall, the prolonged treatment with ciglitazone also seemed to inhibit the hypertrophy of islets in ob/ob mice and protect the structural integrity and viability of islets in db/db mice.