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DOI: 10.1055/s-2007-1003321
© Georg Thieme Verlag, Stuttgart · New York
“In Vitro” Effects of Insulin on the PDH Complex of the Isolated Perfused Heart of Rats Fed a Sucrose-Rich Diet
A preliminary report has been presented in the 3rd International Workshop, Lessons from Animal Diabetes, Jerusalem, Israel, 1980.Publication History
1991
1991
Publication Date:
14 March 2008 (online)
Summary
We have recently reported that the “in situ” myocardial concentrations of the active form of the Pyruvate Dehydrogenase Complex (PDHa) were significantly decreased in hearts obtained from normal rats fed for 3 weeks on an isocaloric sucrose rich (63%) diet (SRD) when compared to age matched controls fed on the standard laboratory chow (STD).
Since, on the one hand SRD rats present glucose intolerance and impaired “in vivo” insulin action and, on the other hand the effects of insulin on the interconversion of heart PDH remains a controversial matter, we found it relevant to study the effects of insulin on the PDH complex in the “in vitro” perfused (Langendorff technique) heart preparations obtained from SRD rats.
After a 35 minute perfusion period with 5.5 mM glucose as the only nutrient in the perfusate, PDHa as a percentage of total PDH was found to remain significantly lower in SRD hearts (M±SEM 32.6±2.3) when compared to STD hearts (68.3±4.6, P < 0.05) in spite of comparable total PDH activities in both groups of animals. Although the addition of insulin to the perfusate (20 mu/ml) resulted in a significant increase in the percentage of PDHa (45.8±3.4) of SRD heart, values attained still remained significantly lower than those obtained in STD controls (67.5±3.6; P < 0.05). Simultaneously, the addition of insulin to the perfusate, significantly reduced the Acetyl-CoA/CoASH ratio in SRD hearts although this ratio remained still much higher than those observed in STD controls under the same experimental conditions.
Work from other investigators (including ourselves) has previously shown that under the same experimental conditions, insulin at even lower concentrations than the presently used was able to fully normalize the decreased PDHa levels present in the heart of insulinopenic rats (induced by either streptozotocin or alloxan). Thus, our findings that high concentrations of insulin were unable to normalize the decreased PDHa levels of SRD hearts indicates that insulin resistance is present in the heart muscle of this nutritionally induced experimental animal model.
Key words
Sucrose-Rich Diet - Pyruvate Dehydrogenase - Heart Muscle - Hypertriglyceridemia