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Non-Essential Role of Dietary Factors in the Development of Diabetes in ob/ob Mice¹

Department of Metabolism and Endocrinology, City of Hope National Medical Center, 1500 East Duarte Rd., Duarte, CA 91010

Hyperinsulinemia is detectable in C57BL/6J ob/ob mice as early as 6 days following birth. Although these mice continue to have very high circulating insulin levels during weaning, they exhibit a transition from mild hypoglycemia to hyperglycemia between 17 and 28 days of age. In the present studies, I examined the roles of the dietary changes associated with weaning (unlimited access to food and its altered composition), and of glucagon and corticosterone overproduction, to the phenotypic differences in glucose regulation observed at this time. The results indicated that neither continuation of the preweaning milk diet nor severely limiting the daily intake of a stock commercial diet significantly affected the initial appearance of glycoregulatory disturbances in ob/ob mice or the maintenance of their hyperinsulinemia. However, the diets reduced the severity of the diabetes. Large phenotype differences in glucagon and corticosterone production were generally associated with the periweaning glycemic changes in both dieted and ad libitum-fed obese mice. Since several previous studies indicate that the tissue responsiveness to insulin is "normal" in ob/ob mice at this time, the increased production of these diabetogenic hormones may contribute to the initial appearance of diabetes.

KEY WORDS: • insulin • diabetes • obesity

¹ Supported by grant AM 19627 from the National Institute of Arthritis, Metabolism and Digestive Diseases.

² Present address: Sansum Medical Research Foundation, Santa Barbara, CA 93102.

Manuscript received 8 December 1980.