An animal model of gestational obesity and prediabetes: HISS-dependent insulin resistance induced by a high sucrose diet in Sprague Dawley rats.

This study developed an animal model of gestational obesity and prediabetes in Sprague Dawley rats using 35% sucrose supplementation (SS). Postprandially, insulin stimulates glucose uptake and nutrient partitioning via insulin-dependent as well as Hepatic Insulin Sensitizing Substance (HISS)-dependent action. HISS is glycogenic in heart, kidney, and skeletal muscle (contrasting insulin's lipogenic actions in liver and adipose tissue) and is responsible for the vasodilatory action of insulin. Post-prandial insulin sensitivity was quantified using the Rapid Insulin Sensitivity Test (RIST). 15-day gestation and virgin animals received SS for 8-weeks (with a 2-week recovery), 10-weeks or 22-weeks. SS in pregnant and virgin rats eliminated HISS-dependent glucose uptake, resulting in compensatory hyperinsulinemia and resultant hypertriglyceridemia and obesity. In groups with SS for 8-weeks followed by a 2-week recovery, there was spontaneous partial recovery of HISS-dependent glucose uptake in virgins and complete recovery in pregnancy. 10-week SS resulted in complete absence of HISS-dependent glucose uptake and produced a model of gestational obesity and prediabetes. 22-week SS did not produce hyperglycemia or worsen hyperinsulinemia but did increase hypertriglyceridemia above 10-week SS. This substantiates the use of 10-week SS as a model of gestational obesity/prediabetes, allowing further studies into treatments of gestational obesity and insulin resistance.