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


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 β cells and surface area and number of pancreatic islets. The β cells of treated ob/ob and db/db mice displayed moderate to heavy granulation whereas most β 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 β 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 β 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 β 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 atrophie 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 β-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 β 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.


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Diani, A.R., Peterson, T., Sawada, G.A. et al. Ciglitazone, a new hypoglycaemic agent. 4. Effect on pancreatic islets of C57BL/6J-ob/ob and C57BL/KsJ-db/db mice. Diabetologia 27, 225–234 (1984).

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Key words

  • Ciglitazone
  • C57BL/6J-ob/ob mice
  • C57BL/KsJ-db/db mice
  • β-cell granulation
  • electron microscopy
  • rough endoplasmic reticulum
  • Golgi apparatus