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 action 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. Postprandial
insulin sensitivity was quantified using the rapid
insulin sensitivity test (RIST). Animals at 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. The 10-week SS resulted in complete absence of HISS-dependent
glucose uptake and produced a model of gestational
obesity and
prediabetes. The 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 and (or)
prediabetes, allowing further studies into treatments of gestational
obesity and
insulin resistance.