ECE2011 Oral Communications Diabetes/Thyroid (6 abstracts)
Hepatic insulin resistance in rats on free-choice high-fat diets
C Diepenbroek 1 , L Eggels 1 , M T Ackermans 2 , E Fliers 1 , M J M Serlie 1 , A Kalsbeek 1 & S E la Fleur 1
1Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands; 2Laboratory of Endocrinology, Department of Clinical Chemistry, Academic Medical Center, Amsterdam, The Netherlands.
Background: Recently, we showed that rats on a free-choice high-fat high-sugar (fcHFHS) diet became rapidly obese and developed glucose intolerance within a week. Interestingly, rats on a free-choice high-fat diet (fcHF), although equally obese and hyperphagic as rats on a fcHFHS diet, did not develop glucose intolerance. Glucose tolerance was also unaffected in rats on a free-choice high-sugar diet, although they consumed more liquid sugar than rats on a fcHFHS diet. Hence, the diet-induced glucose intolerance is specific for rats on a fcHFHS diet. We investigated whether changes in (hepatic) insulin sensitivity contribute to the observed glucose intolerance.
Methods: Male Wistar rats received a jugular vein and carotid artery catheter. After recovery, rats were subjected to either a fcHFHS diet, a fcHF diet or a chow (control) diet for one week. We subsequently performed a hyperinsulinemic-euglycemic clamp, with insulin concentrations two times basal insulin values, combined with stable isotope dilution to measure the decrease in endogenous glucose production (EGP) as a measure of hepatic insulin sensitivity.
Results: Rats on a fcHF and fcHFHS diet increased caloric intake significantly and gained more fat mass compared to rats on chow. EGP suppression by hyperinsulinemia in rats on a fcHFHS diet and on a fcHF diet was more than 50% less compared to suppression in rats on a control chow diet. Moreover, rats on a fcHFHS diet showed a decreased rate of disappearance for glucose compared to chow controls (90 vs 67 μmol/kg min respectively), which was not observed in rats on a fcHF diet.
Conclusions: These data suggest that both obesogenic diets resulted in hepatic insulin resistance whereas a fcHFHS diet also reduced peripheral insulin sensitivity.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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