Glucose transport and glucose transporter GLUT4 are regulated by product(s) of intermediary metabolism in cardiomyocytes

Abstract

Alternative substrates of energy metabolism are thought to contribute to the impairment of heart and muscle glucose utilization in insulin-resistant states. We have investigated the acute effects of substrates in isolated rat cardiomyocytes. Exposure to lactate, pyruvate, propionate, acetate, palmitate, β-hydroxybutyrate or α-oxoglutarate led to the depression of glucose transport by up to 50 %, with lactate, pyruvate and propionate being the most potent agents. The percentage inhibition was greater in cardiomyocytes in which glucose transport was stimulated with the α-adrenergic agonist phenylephrine or with a submaximal insulin concentration than in basal or fully insulin-stimulated cells. Cardiomyocytes from fasted or diabetic rats displayed a similar sensitivity to substrates as did cells from control animals. On the other hand, the amination product of pyruvate (alanine), as well as valine and the aminotransferase inhibitors cycloserine and amino-oxyacetate, stimulated glucose transport about 2-fold. In addition, the effect of pyruvate was counteracted by cycloserine. Since reversible transamination reactions are known to affect the pool size of the citrate cycle, the influence of substrates, amino acids and aminotransferase

Protection of ischemic hearts by high glucose is mediated, in part, by GLUT-4

“…Another limitation of our study is the absence of lactate in perfusion medium. Studies have shown that lactate can be a significant source of energy (7) and that lactate can influence glucose uptake in cardiomyocytes (4). The extent of GLUT-4 translocation during ischemia observed in our study is similar to that demonstrated by Young et al (29) in an in vivo dog model of ischemia.…”

Stereoselective effects of 3-hydroxybutyrate on glucose utilization of rat cardiomyocytes

“…Yet it is notable that ''hhydroxybutyrate'' as well as ''3-hydroxybutyrate'' are often used to represent d-3HB (Christopher et al, 1995;Jovanovic et al, 1998;Boden and Chen, 1999;Alam et al, 2001) or Dl-3HB (Edmond, 1974;Siess, 1985;Poole et al, 1990). Fischer et al reported that administration of 3 mM of hhydroxybutyrate to cardiomyocytes could cause a reduction in glucose uptake to 84% of the control within 1 h (Fischer et al, 1997). On the contrary, Tardif et al showed that incubation of cardiomyocytes with 5 mM of h-hydroxybutyrate for 4 h did not affect glucose uptake (Tardif et al, 2001).…”

EFFECTS OF PYRUVATE ON INTRACELLULAR Ca2+ REGULATION IN CARDIAC MYOCYTES FROM NORMAL AND DIABETIC RATS

“…Diabetes is also associated with a shift from carbohydrate metabolism to increased oxidation of fatty acids. 11–14 The reduced rate of glucose uptake and oxidation is due, in part, to down‐ regulation of GLUT‐4 glucose transporters. 11 Interestingly, the majority of studies comparing the function of diabetic and non‐diabetic hearts have used glucose as the substrate.…”