Polyamines in pancreatic islets of obese-hyperglycemic (ob/ob) mice of different ages

To further evaluate the role of polyamines in insulin production and cell r eplication in diabetic pancreatic islets, we have studied hyperplastic isle ts of obese-hyperglycemic mice of different ages and normal islets of the s ame strain. The aims of the study were to investigate the impact of the dia betic state and aging on polyamine contents and requirements in these islet s. Cultured islets from lean and obese animals contained significantly less polyamines than freshly isolated islets. Spermine-to-spermidine ratio was elevated in freshly isolated islets from young obese mice compared with tho se from lean mice. In islets from old obese animals, spermidine content was decreased, whereas the content of spermine was not different from that of young obese mice. The physiological significance of polyamines was investig ated by exposing islets in tissue culture to inhibitors of polyamine synthe sis. This treatment caused a partial polyamine depletion in whole islets bu t failed to affect polyamine content of cell nuclei. Insulin content was no t affected in polyamine-deficient islets of obese mice, irrespective of age , in contrast to decreased islet insulin content in polyamine-depleted youn g lean animals. Polyamine depletion depressed DNA synthesis rate in obese m ouse islets; in lean mice it actually stimulated DNA synthesis. We conclude d that important qualitative and quantitative differences exist between isl ets from obese-hyperglycemic and normal mice with respect to polyamine cont ent and requirements of polyamines for regulation of insulin content and ce ll proliferation. The results suggest that spermine may be involved in medi ating the rapid islet cell proliferation noted early in obese-hyperglycemic syndrome, but changes in spermine concentration do not seem to account for the decline in islet cell DNA synthesis in aged normoglycemic animals.