In vivo insulin resistance during pregnancy in the rat

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Abstract
The glucose disappearance rate measured after IV glucose injection (1 g/kg body wt) remained unchanged between 12 and 21 day of gestation in the rat. In contrast, insulin secretion in response to IV glucose was markedly increased on day 19 and 21 of pregnancy, suggesting resistance to endogenous insulin. Glucose kinetics (glucose production, utilization and clearance) in response to various doses of IV insulin have been studied in anaesthetised postabsorbtive 19 day pregnant and virgin rats using 6-3H glucose. With the supramaximal dose of insulin (4 U/kg body wt) no differences in glucose kinetics were found between pregnant and virgin rats. In contrast, with the two lower doses of insulin (0.15 and 0.05 U/kg body wt) glucose production was inhibited by 36±3% and 13±2% (Mean±SEM) respectively in virgin rats, but was not decreased in pregnant rats. When the effect of insulin on glucose clearance was expressed as % of the maximal effect obtained with 4 U/kg body weight, the rise in glucose clearance in response to the two lower doses of insulin (0.15 and 0.05 U/kg body wt) was lower in pregnant (57.5±6 and 27.4±4%) than in virgin rats (73.3±6 and 42.2±7%). These results suggest that a decreased sensitivity to insulin appears in late pregnancy in the rat and could involve both liver and skeletal muscle.