The effects of chronic diabetes and physiological insulin concentration on ketone bodies metabolism in the heart.

Abstract

In this study the effects of filter-type (Millipore and Whatman No. 54), albumin and insulin at physiological and non-physiological concentrations (12000, 1200, 600, 480, and 300 pM) on D-3-hydroxybutyrate (D-3-HB) utilization and oxidation and acetoacetate production by the isolated nonworking perfused heart from normal and diabetic (4-week) rats was investigated. The use of Whatman No. 54 paper filter to filter the perfusate, in contrast to Millipore filter (0.4 mm) porisity, resulted in the elevation of the rates of utilization and oxidation of D-3-HB and had no effect on acetoacetate production in hearts from normal or diabetic (4-week) rats. Albumin inhibited the utilization and oxidation of D-3-HB, suppressed the percentage of D-3-HB oxidation, increased the percentage of acetoacetate production and had no effect on acetoacetate production in hearts from normal or diabetic rats. Regardless of the filter type and the presence or absence of albumin, the utilization and oxidation of D-3-HB are inhibited and no effect on acetoacetate production was observed in hearts from diabetic rats. Insulin at physiological and non-physiological concentrations in the presence of albumin affects the metabolism of D-3-HB; the stimulations of D-3-HB utilization averaged 32% and 46% in hearts from normal and diabetic rats respectively. The stimulation of D-3-HB oxidation averaged 40% and 60% in hearts from normal and diabetic rats respectively. The D-3-HB utilization and oxidation rates were higher in the hearts isolated from normal rats. No effect of insulin on the rate of acetoacetate production in hearts from normal or diabetic rats was observed, with the exception of an insulin concentration of 1200 pM; there was a 54% reduction in hearts from normal rats. Insulin at 12000 pM had no effect on D-3-HB utilization and oxidation and acetoacetate production in hearts from normal or diabetic rats when perfused using Whatman paper filters in the absence of albumin, but it enhanced the utilization and oxidation of D-3-HB when Millipore paper filters were used.