Insulin replacement therapy in diabetic rats using an osmotic pump normalizes protein and mrna levels of enzymes key to hepatic carbohydrate metabolism

In previous studies we demonstrated the failure of hepatic protein and mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK), glycogen synthase (GS) and glycogen phosphorylase (GP) to return to control levels in the insulininjected diabetic rat. The purpose of this study was to determine whether these results are a consequence of the insulin replacement therapy or a new homeostasis resulting from the diabetic condition. Alloxan-diabetic rats received similar amounts of insulin for 5 days, either by twice daily injections (TDI) or continuous subcutaneous infusion (CSI) using an Alzet osmotic pump. While TDI brought blood glucose levels within normal limits, there were transient hyperglycémie fluctuations between injections over a 24 hour period. These variations in blood glucose levels were not observed in the CSI animals which were strictly controlled at normal levels. PEPCK, GS and GP protein and mRNA from TDI rats were identical to those previously observed. In contrast, all the aforementioned protein and mRNA levels returned to control levels in CSI-treated animals. This data emphasizes the effects of altered blood glucose levels on hepatic carbohydrate metabolism, and further emphasizes the importance of strictly regulating blood glucose in the treatment of insulin-dependent diabetes.