The effect of insulin on the uptake and metabolic fate of glucose in isolated perfused hearts of dyslipemic rats

Male Wistar rats chronically (15 weeks) fed a sucrose-rich diet (SRD; 63% w /w) developed hypertriglyceridemia and impaired glucose homeostasis. Hearts from these animals rr ere isolated and perfused using the Langendorff reci rculating method. Glucose at levels similar to those found in the animal in vivo was used is the only exogenous substrate. The hearts were perfused fo r 30 minutes in the presence or absence of insulin (30 mU/mL) in the perfus ion medium. In the absence of the hormone, glucose uptake was impaired and the glucose utilization uns reduced, with a significant increase of lactate release. Glucose oxidation, which was estimated from the activation state of the enzyme pyruvate dehydrogenase complex (PDHc), was depressed mainly d ue to both an increase of PDH kinase and a decrease of PDHa (active Sonn of PDHc) activities. Although the addition of insulin in the perfusion medium improved the above parameters, it was unable to normalize them. The presen t results suggest that at least two different mechanisms might contribute t o insulin resistance and to the impaired glucose metabolism in the perfused hearts of the dyslipemic SRD-fed animals: (1) reduced basal and insulin-st imulated glucose uptake and its utilization or (2) increased availability a nd oxidation of lipids (low PDHa and high PDH kinase activities), which in trim decrease glucose uptake and utilization. Thus, this nutritional experi mental model may be useful to study how impaired glucose homeostasis, incre ases plasma free fatty acid levels and hypertriglyceridemia could contribut e to heart tissue malfunction. (J. Nutr. Biochem. 11: 39-37, 2000) (C) Else vier Science Inc. 2000. All rights reserved.