Insulin action during fasting and refeeding in rat determined by euglycemic clamp

To further characterize the role of insulin in glucose metabolism during fasting and refeeding, euglycemic-hyperinsulinemic clamps were performed in control, 3 day-fasted, and 3 day-fasted then 3 day-refed rats. Glucose production and utilization were measured by using [3-3H]glucose. In control and refed rats, hepatic glucose production was totally suppressed at insulin concentration higher than 500 microU/ml; by contrast, during fasting, hepatic glucose production was not suppressed even at insulin concentration tenfold higher. Maximal increment of glucose utilization was lower in fasted than in control rats. Three days of refeeding restored almost entirely normal responses to insulin for glucose utilization. Blood glucose concentration was clamped at a different level in fasted and in control and refed rats; however, increment in glucose clearance in response to insulin was lower in fasted rats than in the two other groups. Thus fasting produces a state of insulin unresponsiveness both at the hepatic and peripheral levels, normal responsiveness being restored after 3 days of refeeding.