ONTOGENIC CHANGES IN PROGLUCAGON MESSENGER-RNA IN BB DIABETES-PRONE AND NORMAL RATS WEANED ONTO A CHOW DIET

Weaning onto chow diets causes the highest incidence of diabetes in th e BE rat. Changes in gut development and absorption of nutrients in th e diabetes prone sat and the subsequent effect on pancreatic function may play a role in the ultimate development of the disease. BE diabete s prone (dp) and BE normal (n) dams were fed chow diets. Pups were kil led at Various ages ranging from 7 to 30 days. BBdp rats had higher sm all intestine and colon weights expressed per body weight at all ages (p < 0.0001). RNA content (mg/g) in the jejunum, ileum and colon was h igher in the BBdp rats beginning at the critical period at 21 days and maintained at 24 days and 30 days (p < 0.0001). Proglucagon message d ecreased with age in both BBdp and BBn animals (p < 0.0001). Levels of proglucagon mRNA were higher in BBdp compared to BBn animals only in the ileum at 10 days (p < 0.01). Adjusting for total ileal and colonic RNA content resulted in BBdp animals having higher total colonic prog lucagon mRNA at 21, 24 and 30 days (p < 0.0001). Plasma GLP-1(7-36) am ide was more than doubled in BBdp compared to BBn animals (p < 0.0005) at 30 days. Expressing sodium-dependent D-glucose co-transporter (SGL T-1), GLUT2 and GLUT5 mRNA per total jejunal RNA shows increased trans porter mRNA in BBdp compared to BBn rats at weaning (21 days) (p < 0.0 5). Radical differences exist between BBdp and BBn animals at 'critica l periods' in both proglucagon and glucose transporter gene expression . These differences may help explain altered growth and diseases incid ence between these two strains [Diabetologia (1997) 40: 871-878].