Peripheral
hyperinsulinemia resulting from subcutaneous
insulin injection is associated with metabolic defects which include abnormal
glucose metabolism. The first aim of this study was to quantify the impairments in liver and muscle
glucose metabolism that occur when
insulin is delivered via a peripheral vein compared to when it is given through its endogenous secretory route (the hepatic portal vein) in overnight fasted conscious dogs. The second aim was to determine if peripheral delivery of a hepato-preferential
insulin analog could restore the physiologic response to
insulin that occurs under meal feeding conditions. This study is the first to show that hepatic
glucose uptake correlates with
insulin's direct effects on the liver under hyperinsulinemic-hyperglycemic conditions. In addition,
glucose uptake was equally divided between the liver and muscle when
insulin was infused into the portal vein, but when it was delivered into a peripheral vein the percentage of
glucose taken up by muscle was 4-times greater than that going to the liver, with liver
glucose uptake being less than half of normal. These defects could not be corrected by adjusting the dose of peripheral
insulin. On the other hand, hepatic and non-hepatic
glucose metabolism could be fully normalized by a hepato-preferential
insulin analog.