RT Journal Article SR Electronic T1 13C NMR studies of glucose disposal in normal and non-insulin-dependent diabetic humans JF Philosophical Transactions of the Royal Society of London. Series A: Physical and Engineering Sciences JO Philos Trans Phys Sci Eng FD The Royal Society SP 525 OP 529 DO 10.1098/rsta.1990.0180 VO 333 IS 1632 A1 A1 A1 YR 1990 UL http://rsta.royalsocietypublishing.org/content/333/1632/525.abstract AB To examine the extent to which the defect in insulin action in subjects with non-insulin-dependent diabetes mellitus (NIDDM) can be accounted for by impairment of muscle glycogen synthesis, we performed combined hyperglycemic-hyperinsulinemic clamp studies with [13C]glucose in five subjects with NIDDM and in six age- and weight-matched healthy subjects. The rate of incorporation of intravenously infused [1-13C]glucose into muscle glycogen was measured directly in the gastrocnemius muscle by means of a nuclear magnetic resonance (NMR) spectrometer with a 15.5 min time resolution and a 13C surface coil. The steady-state plasma concentrations of insulin (ca. 400 pmol l-1) and glucose (ca. 10 mmol l-1) were similar in both study groups. The mean (±SE) rate of glycogen synthesis, as determined by 13C NMR, was 78 ± 28 and 183 ± 39 (imol-glucosyl units (kg muscle tissue (wet mass))-1 min-1 in the diabetic and normal subjects, respectively (p < 0.05). The mean glucose uptake was markedly reduced in the diabetic (30 ± 4 pmol kg-1 min-1) as compared with the normal subjects (51 ± 3 pmol kg-1 min-1; p < 0.005). The mean rate of non-oxidative glucose metabolism was 22 ± 4 pmol kg-1 min-1 in the diabetic subjects and 42 ± 4 pmol kg-1 min-1 in the normal subjects (p < 0.005). When these rates are extrapolated to apply to the whole body, the synthesis of muscle glycogen would account for most of the total-body glucose uptake and all of the non-oxidative glucose metabolism in both normal and diabetic subjects. We conclude that muscle glycogen synthesis is the principal pathway of glucose disposal in both normal and diabetic subjects and that defects in muscle glycogen synthesis have a dominant role in the insulin resistance that occurs in persons with NIDDM.