grantor:
University of TorontoIn our previous studies in normal dogs and humans, insulin had both a peripheral extrahepatic effect and a direct effect in suppressing glucose production (GP) whereas the direct effect was undetectable in moderately hyperglycemic diabetic dogs. The purpose of this thesis was to investigate whether euglycemia restores the direct effect of insulin on GP in diabetic dogs. Insulin was infused portally (POR) or peripherally at half the rate (1/2PER) to match the peripheral insulin levels and therefore obtain a selective POR vs. 1/2PER difference in hepatic insulin levels. A greater suppression of GP was seen with POR than 1/2PER during euglycemia. The effect of portal (POR REPL) vs. peripheral basal replacement doses (PER REPL) was also analyzed. To obtain the same basal euglycemia, a greater degree of peripheral insulinemia was required with PER REPL than POR REPL which is also consistent with a direct effect of insulin in suppressing GP. Therefore, acute insulin-induced restoration of euglycemia in diabetic dogs restores the direct hepatic effect of insulin on GP. Our studies show that the physiological route of insulin delivery results in better regulation of GP and in less peripheral hyperinsulinemia than the peripheral route.M.Sc
