The Fate of [U-13C]Palmitate Extracted by Skeletal Muscle in Subjects With Type 2 Diabetes and Control Subjects

Abstract

The current study investigated the fate of a [U-13 C] palmitate tracer extracted by forearm muscle in type 2 diabetic and control subjects. We studied seven healthy lean male subjects and seven obese male subjects with type 2 diabetes using the forearm muscle balance technique with continuous intravenous infusion of the stable isotope tracer [U-13 C]palmitate under baseline conditions and during intravenous infusion of the nonselective ␤-agonist isoprenaline (ISO; 20 ng ⅐ kg ؊1 lean body mass ⅐ min ؊1 ). In skeletal muscle of control subjects, there was a significant release of 13 C-labeled oxidation products in the form of 13 CO 2 (15% of 13 C uptake from labeled palmitate) and a significant release of 13 C-labeled glutamine (release of 13 C-labeled atoms from glutamine was 6% of 13 C uptake from labeled palmitate), whereas in type 2 diabetic subjects there was no detectable release of 13 CO 2 and 13 C-glutamine, despite a significant uptake of [U-13 C]palmitate (60% of control value). There was net uptake of arterial 13 Clabeled glutamate by forearm muscle in both groups. Also, the ISO-induced increase in arterial glutamine enrichment and arterial concentration of 13 C-glutamine was more pronounced in the diabetic group relative to control subjects. In view of the diminished ISO-induced release of 13 C-glutamine from type 2 diabetic muscle, the latter data indicate that more [U-13 C]palmitate entered the liver in the diabetic group and was incorporated into newly synthesized glutamine and glutamate molecules. Thus, the lack of release of 13 C-labeled oxidation products by type 2 diabetic muscle during ␤-adrenergic stimulation, despite significant [U-13 C]-palmitate uptake, indicates differences in the handling of fatty acids between type 2 diabetic subjects and healthy control subjects. Diabetes 51:784 -789, 2002

Substrate source utilisation in long-term diagnosed type 2 diabetes patients at rest, and during exercise and subsequent recovery

“…The present data are not necessarily in contrast to previous findings, which generally show reduced NEFA uptake and/or oxidation rates over the leg or arm in recently diagnosed type 2 diabetes patients [11,14,16,20,45]. The greater whole-body NEFA turnover rate in long-termdiagnosed type 2 diabetes patients observed in the present study is most likely attributable to the presence of adipose tissue insulin resistance and the absence of compensating hyperinsulinaemia in the selected patient group.…”

Membrane Fatty Acid Transporters as Regulators of Lipid Metabolism: Implications for Metabolic Disease

“…It was initially reported that skeletal muscle fatty acid uptake in human muscle is reduced in type 2 diabetes (35,476). However, these observations are likely incorrect, because these conclusions appear to be based on problematic, indirect measurements, and the data do not concur with more recent direct determination of fatty acid transport rates across the plasma membrane in muscles of diabetic animals (71,387) or humans with type 2 diabetes (48).…”

Determinants of intramyocellular triglyceride turnover: implications for insulin sensitivity

“…Skeletal muscle oxidative capacity, on the other hand, has been shown to be predictive of insulin action when sedentary and physically active individuals are studied (16). A reduction in fatty acid oxidation in skeletal muscle has been reported in obese and type 2 diabetic individuals in postabsorptive conditions (9,10,65,112). This observation is more controversial when subjects are performing exercise where whole body fat oxidation has been found to be either reduced (86) or increased (14,15,37) compared with lean control.…”