Effects of nutritional status and acute variation in substrate supply on cardiac and skeletal-muscle fructose 2,6-bisphosphate concentrations

Abstract

We examined the long-term effects of nutritional status and the acute effects of changes in exogenous carbohydrate- and lipid-substrate supply and utilization on fructose 2,6-bisphosphate (Fru-2,6-P2) concentrations in heart, gastrocnemius and soleus. Starvation decreased Fru-2,6-P2 concentrations in all three muscles. The acute administration of insulin and glucose increased skeletal-muscle Fru-2,6-P2 in the fed, but not in the starved, state, but cardiac Fru-2,6-P2 was unchanged. Cardiac and skeletal-muscle Fru-2,6-P2 concentrations were unaffected by acute increases in fatty acid supply produced by the administration of corn oil plus heparin, or by acute decreases in fatty acid supply produced by inhibition of lipolysis. Differences in cardiac and skeletal-muscle Fru-2,6-P2 concentrations observed in response to starvation were not reversed by administration of glucose or glucose plus insulin, or by inhibition of lipolysis, even though changes in citrate (heart), acylcarnitine (heart) and glycogen (skeletal muscle) were observed. Concentrations remained low for at least 8 h after chow re-feeding, but the fed value was restored by 24 h.

The relationship between changes in lipid fuel availability and tissue fructose 2,6-bisphosphate concentrations and pyruvate dehydrogenase complex activities in the fed state

“…Concentrations of glucose and the ketone bodies were measured in KOH-neutralized HC104 extracts of whole blood, concentrations of non-esterified fatty acids (NEFA) in plasma, and concentrations of free and acylated carnitine, citrate and Fru-2,6-P2 in extracts offreeze-clamped tissues (see ref. [6] for details).…”

“…Sources of material were as in [6]. 5-Methylpyrazole-3-carboxylic acid (MPCA) was generously given by Upjohn Ltd., Crawley, West Sussex, U.K.…”

“…in 0.2 ml of 0.9 NaCl, pH 7.4, intraperitoneally) at 2.5 h before the rats were killed. An elevation of fatty acid concentration was achieved by the administration of corn oil followed by heparin as detailed previously [6]. Rats were sampled at 1 or 2 h after heparin injection.…”

“…In vitro, exogenous fatty acid decreases the percentage of PDH in the active form [11,12], decreases the concentration of Fru-2,6-P2 [7], and inhibits flux through PFK-1 [7]. The [6]. Moreover, when lipid fuel con-centrations are decreased in response to re-feeding after starvation, restoration of hepatic PDH activity precedes any change in the Fru-2,6-P2 concentration [10].…”

“…[4]). The glucose-sparing effect of lipid-derived fuels has been demonstrated in working muscles in starvation [5,6], and can be reproduced in perfused hearts from fed rats by the provision of ketone bodies or acetate [1][2][3][4][5][6][7]. PDH is inactivated [1], and specific inhibition of PFK-1 has been demonstrated by measurements of the detritiation of [3-3H]glucose [7].…”