CHICK, WILLIAM L., AND ARTHUR, A. LIKE. Effects of diet on pancreatic beta cell replication in mice with hereditary diabetes. Am. J. Physiol. 22 l (1): 202-208. 1971.-The effects of caloric intake and dietary composition on beta cell replication were studied in diabetic mutant(C57BL/Ks-dbdb) mice. Mitotic activity was evaluated following thymidine-3H administration both by autoradiography and by determining islet DNA specific activity (DPM/pg islet DNA). Food restriction early in the diabetic syndrome reduced hyperglycemia and hyperinsulinemia and resulted in low incorporation of label. Animals refed ad libitum with either commercial laboratory chow or with a synthetic diet containing a combination of carbohydrate, protein, and fat showed the greatest increases in labeling. This was associated with rises in both blood glucose and serum insulin levels. Mice refed with only protein had a lower daily caloric intake and remained normoglycemic. Despite this, both serum insulin levels and the incorporation of label were significantly increased. Mice refed with carbohydrate alone remained normoglycemic and showed only a small rise in serum insulin. There was no increased labeling, even though daily caloric intake was similar to that with the protein diet. Increased beta cell mitotic activity therefore occurred in the absence of hyperglycemia, but not in the absence of hyperinsulinemia. diabetic mutant mouse; genotype C57BL,‘Ks-dbdb; mutation; pancreatic islets; islets of Langerhans; mitotic activity; glucose; insulin; food restriction

RECENT STUDIES suggest that limitation of the capacity to form new beta cells may be a fundainental factor in determining the onset and severity of hereditary diabetes. An absolute decrease in beta cell nuinbers has been reported in human diabetes and is most marked in the juvenile form (9). In addition, in laboratory rodents with spontaneous diabetes, the disease is most severe, and frcqucntly lethal in those strains (C57BL/Ks-d6d6 mouse, Chinese hamster) with only a limited capacity for beta cell replication, and hence a limited ability to expand the insulin synthetic capacity (4, 5, 6, 17, 18). In contrast, rodents with a greater ability to produce IUZW beta cells (Egvptian sand rat, obese (06) mouse, and C3Hf XI F1 mouse) generally overcome their rclativc insulin deficiency with amelioration of the diabetic syndrome (2, 19, 20). Previous reports from our laboratory(6, 17, 18) have indicated that the diabetic mutant mouse (C57BL/Ksdbdb) is a useful niodel for studying the factors which regulate beta cell proliferative activity in expcrimen tal heredi tarv diabetes. Beta ccl1 rnitotic activity was determined following