Studies in the diabetic mutant mouse: III. Physiological factors associated with alterations in beta cell proliferation

Summary 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/g 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.USPHS Research Career Development Awardee, Grant K4-AM-7394.