Time Course of Serum Glucoregulatory Variables and Lipids following Neonatal Thymectomy of Diabetes-Prone and Control BB Wistar Rats Fed a Defined Diet

Abstract

The acute diabetic syndrome in the BB Wistar rat resembles human type 1 (insulin-dependent) diabetes, including a possible association with T cell-mediated, (auto)immune processes. In most previous studies ‘normoglycemic’ littermates of diabetic BB rats have been used as controls and little attention has been paid to the role of diet. It now appears that asymptomatic/diabetes-prone littermates of diabetics have immune system defects as well as metabolic abnormalities. Since there are also indicators that the disease process starts before animals become symptomatic, we looked for prospective metabolic changes in prediabetic, asymptomatic/diabetes-prone and control (diabetes-free) BB rats following intervention in the immune system while maintaining the animals on a defined diet (AIN-76). The results reported here confirm and extend the finding of Like et al. (1982) that neonatal thymectomy reduces the frequency of the syndrome and emphasize the role of diet in modifying its expression. In contrast to previous reports of hyperglucagonemia only after onset of diabetes, asymptomatic/diabetes-prone animals had periodic increases of plasma glucagon values up to 3-fold those of diabetes-free controls; prediabetics displayed a similar pattern. Asymptomatic/diabetes-prone rats also tended to have slightly higher blood cholesterol levels. The low incidence and delayed onset of the syndrome in rats fed a modified AIN-76 diet (27%, 127 ± 21 days) compared to the previous chow-fed generation (60%, 93 ± 18 days) and chow-fed littermates (38%, 87 ± 16 days) suggested that diet can modify expression of the syndrome.