Beta cell replication was studied in normal (C 57 BL/Ks) and diabetic mutant (C 57 BL/Ks-db/db) mice following thymidine-3H administration. The specific activity of DNA of isolated islets (DPM/μg islet DNA) was used as an index of proliferative activity and correlated with labeling determined by radioautography. Although thymidine-3H incorporation in islets of prehyperglycemic 5 to 6 week old mutants was limited, it was significantly greater than that in normal mice. With the elevation of blood glucose values, incorporation rose sharply, reaching a maximum level above 130 mg glucose/100 ml blood. Sustained, severe hyperglycemia subsequently correlated with a decline in islet DNA synthesis. Food restriction early in the syndrome reduced hyperglycemia and resulted in low incorporation of label. Animals refed ad lib for periods of 1, 2, or 3 weeks showed significant increases in labeling, with maximal values after 1 week of refeeding. Electron microscopic radioautographs of the islets revealed labeled beta cells but no labeled alpha cells, suggesting that proliferative activity is predominantly restricted to the beta cell population.
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