Glucose-free fatty acid cycle operates in human heart and skeletal muscle in vivo.

Abstract

Positron emission tomography permits noninvasive measurement of regional glucose uptake in vivo in humans. We employed this technique to determine the effect of FFA on glucose uptake in leg, arm, and heart muscles. Six normal men were studied twice under euglycemic hyperinsulinemic (serum insulin -500 pmol/liter) conditions, once during elevation of serum FFA by infusions of heparin and Intralipid (serum FFA 2.0±0.4 mmol/liter), and once during infusion of saline (serum FFA 0.1±0.01 mmol/liter). Regional glucose uptake rates were measured using positron emission tomography-derived 'Ffluoro-2-deoxy-D-glucose kinetics and the three Elevation of plasma FFA decreased whole body glucose uptake by 31±2% (1,960±130 vs. 2,860±250 Mmol/min, P < 0.01, FFA vs. saline study). This decrease was due to inhibition of glucose uptake in the heart by 30±8% (150±33 vs. 200±28 smol/min, P < 0.02), and in skeletal muscles; both when measured in femoral (1,594±261 vs. 2,272±328 Mmol/ min. 25+13%) and arm muscles (1,617±411 to 2,305±517Mmol/min, P < 0.02, 31±6%). Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.75, P < 0.005), and arm muscles (r = 0.69, P < 0.05) but not with glucose uptake in the heart (r = 0.04, NS). These data demonstrate that the glucose-FFA cycle operates in vivo in both heart and skeletal muscles in humans. (J.

Myocardial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in Type 2 diabetic patients

“…The clinical implications of the present study support the role of high TGs and FFAs in the development of long-term adverse effects on myocardial function reported by Nuutila et al (23).…”

Abnormal myocardial kinetics of 123 I-heptadecanoic acid in subjects with impaired glucose tolerance

“…Increased lipid turnover rate and elevated NEFA concentration lead to increased triglyceride accumulation, enhanced lipid oxidation and further to inhibition of glycolysis and glucose oxidation [12,30]. The glucose-fatty acid cycle initially described by Randle et al [31] has been shown to be present also in the human heart: increased fatty acid oxidation inhibits glucose oxidation delete [32]. However, data concerning myocardial metabolism in NIDDM and IGT patients are scarce, and it is not known whether myocardial substrate utilization is altered in these conditions.…”

“…According to the glucose-fatty acid cycle [31,32], hyperglycaemia could result in depression of myocardial NEFA utilization. However, even though IGT subjects were normoglycaemic during the study, they still had the most abnormal HDA kinetics.…”

“…This perfusion phase is followed by two elimination phases. The first elimination phase is considered to represent beta-oxidation, k 32 , and it is clinically the most important. The parameter k 42 mainly reflects esterification of NEFA-CoA into a slow turnover pool.…”

Brown Adipose Tissue in Humans

“…Mathematical modeling becomes mandatory when the effects of hormones and nutrients on brown fat activity are studied. During insulin stimulation muscle glucose uptake is up to six--fold enhanced and covers 60--70% of the whole body glucose utilization (Nuutila et al 1992). Therefore 18 FDG is cleared from the plasma into muscles, its availability in plasma is decreased and 'counts' are lower in BAT.…”