The fate of [U-13C] palmitate extracted by skeletal muscle in subjects with type 2 diabetes and control subjects

The current study investigated the fate of a [U-Cl-13 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-C-13]palmitate under baseline conditions and during intravenous infusion of the nonselective P-agonist isoprenaline (ISO; 20 ng (.) kg(-1) lean body mass (.) min(-1)). In skeletal muscle of control subjects, there was a significant release of C-13-labeled oxidation products in the form of (CO2)-C-13 (15% of C-13 uptake from labeled palmitate) and a significant release of 13 C-labeled glutamine (release of 13 C-labeled atoms from glutamine was 6% of C-13 uptake from labeled palmitate), whereas in type 2 diabetic subjects there was no detectable release of (CO2)-C-13 and C-13-glutamine, [U-C-13]palmitate (60% of despite a significant uptake of [U-C-13] 60% of control value). There was net uptake of arterial C-13-labeled glutamate by forearm muscle in both groups. Also, the ISO-induced increase in arterial glutamine enrichment and arterial concentration of C-13-glutamine was more pronounced in the diabetic group relative to control subjects. In view of the diminished ISO-induced release of C-13-glutamine from type 2 diabetic muscle, the latter data indicate that more [U-13C]palmitate entered the liver in the diabetic group and was incorporated into newly synthesized glutamine and glutamate molecules. Thus, the lack of release of C-13-labeled oxidation products by type 2 diabetic muscle during beta-adrenergic stimulation, despite significant [U-C-13]- palmitate uptake, indicates differences in the handling of fatty acids between type 2 diabetic subjects and healthy control subjects.