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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

Summary

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.

References

  1. 1.

    Chang AY, Wyse BM, Gilchrist BJ, Peterson T, Diani AR (1983) Ciglitazone, a new hypoglycemic agent. I. Studies in ob/ob and db/db mice, diabetic Chinese hamsters, and normal and streptozotocin-diabetic rats. Diabetes 32: 830–838

  2. 2.

    Chang AY, Wyse BM, Gilchrist BJ (1983) Ciglitazone, a new hypoglycemic agent. II. Effect on glucose and lipid metabolisms and insulin binding in the adipose tissue of C57BL/6J-ob/ob and - + /? mice. Diabetes 32: 839–845

  3. 3.

    Chang AY, Gilchrist BJ, Wyse BM (1983) Ciglitazone, a new hypoglycaemic agent. 3. Effect on glucose disposal and gluconeo-genesis in vivo in the C57BL/6J-ob/ob and - + /? mice. Diabetologia 25: 514–520

  4. 4.

    Lloyd B, Burrin J, Smythe P, Alberti KGMM (1978) Enzymic fluorometric continuous-flow assays for blood glucose, lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate. Clin Chem 24: 1724–1729

  5. 5.

    Zaharto DS, Beck LV (1968) Studies of a simplified plasma insulin immunoassay using cellulose powder. Diabetes 17: 444–457

  6. 6.

    Chang AY, Noble RE, Wyse BM (1977) Streptozotocin-induced diabetes in the Chinese hamster. Biochemical and endocrine disorders. Diabetologia 13: 596–602

  7. 7.

    Begin-Heick N, Heick HM, Norman MG (1979) Regranulation of islets of Langerhans and normalization of in vivo insulin secretion in ob/ob mice treated with oxytetracycline. Diabetes 28: 65–70

  8. 8.

    Mahler RJ, Szabo O (1971) Amelioration of insulin resistance in obese mice. Am J Physiol 221: 980–983

  9. 9.

    Solomon J, Bulkley RJ, Mayer J (1974) Effect of a low dose of alloxan on blood glucose, islet beta cell granulation, body weight and insulin resistance of ob/ob mice. Diabetologia 10: 709–715

  10. 10.

    Dalpe-Scott M, Heick HMC, Begin-Heick N (1982) Oxytetracycline treatment improves the response to insulin in the spontaneously diabetic (BB) rat. Diabetes 32: 53–59

  11. 11.

    Hiatt N, Bonorris G (1970) Insulin response in pancreatectomized dogs treated with oxytetracycline. Diabetes 19: 307–311

  12. 12.

    Coleman DL, Hummel KP (1973) The influence of genetic background on the expression of the obese (ob) gene in the mouse. Diabetologia 9: 287–293

  13. 13.

    Boquist L (1977) Differences in the expressions of spontaneous and induced diabetes in Chinese hamsters, Mongolian gerbils and C57BL/KsJ and C57BL/6J mice. Int Congr Ser Excerpta Medica 413: 683–690

  14. 14.

    Hummel KP, Coleman DL, Lane PW (1972) The influence of genetic background on expression of mutations at the diabetes locus in the mouse. I. C57BL/KsJ and C57BL/6J strains. Biochem Genet 7: 1–3

  15. 15.

    Boquist L, Hellman B, Lernmark A, Taljedal IB (1974) Influence of the mutation ‘diabetes’ on insulin release and islet morphology in mice of different genetic backgrounds. J Cell Biol 62: 77–89

  16. 16.

    Baetens D, Stefan Y, Ravazzola M, Malaisse-Lagae F, Coleman DL, Orci L (1978) Alteration of islet cell populations in spontaneously diabetic mice. Diabetes 27: 1–7

  17. 17.

    Hummel KP, Dickie MM, Coleman DL (1966) Diabetes, a new mutation in the mouse. Science 153: 1127–1128

  18. 18.

    Coleman DL, Hummel KP (1967) Studies with the mutation, diabetes, in the mouse. Diabetologia 3: 238–248

  19. 19.

    Like AA, Chick WL (1970) Studies in the diabetic mutant mouse: I. Light microscopy and radioautography of pancreatic islets. Diabetologia 6: 207–215

  20. 20.

    Like AA, Chick WL (1970) Studies in the diabetic mutant mouse: II. Electron microscopy of pancreatic islets. Diabetologia 6: 216–242

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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). https://doi.org/10.1007/BF00273811

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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