Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/11/2000
Publication Date: 6/1/2000
Citation: HANKARD, R.G., HAYMOND, M., DARMAUN, D. ROLE OF GLUCOSE IN THE REGULATION OF GLUTAMINE METABOLISM IN HEALTH AND IN TYPE 1 INSULIN-DEPENDENT DIABETES. AMERICAN JOURNAL OF PHYSIOLOGY ENDOCRINOLOGY AND METABOLISM. 2000. Interpretive Summary: Glutamine, the most abundant free amino acid in the body, is at the crossroads of protein and carbohydrate metabolisms. Glutamine serves as a major carbon donor for gluconeogenesis in humans. Conversely, glucose serves as precursor for glutamine's carbon skeleton. A glucose-glutamine cycle might operate in humans, yet it remains to be determined whether glucose availability affects estimates of glutamine synthesis, and, if so, whether this effect is mediated via increased insulin secretion. Glucose, glutamine and leucine kinetics were studied using two 4 h tracer infusion studies performed on two consecutive days in healthy volunteers and in patients with insulin dependent diabetes mellitus. In both studies, volunteers were studied under mild hyperglycemic condition on one day and normal plasma glucose levels maintained on the second day. This was done to study the role of glucose in the regulation of glutamine metabolism in both groups. A stable isotope tracer in a primed continuous infusion was used in all studies and study groups. It was determined that 1) the contribution of glucose to the estimated rate of glutamine synthesis does not increase when elevation of plasma glucose results from insulin deficiency, and 2) the transfer of carbon from glucose to glutamine may depend on insulin availability.
Technical Abstract: To determine the effect of glucose availability on glutamine metabolism, glutamine kinetics were assessed under conditions of hyperglycemia resulting from 1) intravenous infusion of 7.5% dextrose in healthy adults and 2) insulin deficiency in young adults with insulin-dependent diabetes mellitus (IDDM). Eight healthy adults and five young adults with IDDM were studied in the postabsorptive state by use of a primed continuous infusion of D-[U-14C]glucose, L-[5,5,5-2H3]leucine, and L-[3,4-13C]glutamine. Whether resulting from insulin deficiency or dextrose infusion, the rise in plasma glucose was associated with increased glucose turnover (23.5 ± 0.7 vs. 12.9 ± 0.3 µmol · kg-1 · min-1, P < 0.01 and 20.9 ± 2.5 vs. 12.8 ± 0.4 µmol · kg-1 · min-1, P = 0.03, in health and IDDM, respectively). In both cases, high blood glucose failed to alter glutamine appearance rate (Ra) into plasma [298 ± 9 vs. 312 ± 14 µmol · kg-1 · h-1, not significant (NS) and 309 ± 23 vs 296 ± 26 µmol · kg-1 · h-1, NS, in health and IDDM, respectively] and the estimated fraction of glutamine Ra arising from de novo synthesis (210 ± 7 vs. 217 ± 10 µmol · kg-1 · h-1, NS and 210 ± 16 vs. 207 ± 21 µmol · kg-1 · h-1, NS, in health and IDDM, respectively). When compared with the euglycemic day, the apparent contribution of glucose to glutamine carbon skeleton increased when high plasma glucose resulted from intravenous dextrose infusion in healthy volunteers (10 ± 0.8 vs. 4.8 ± 0.3%, P < 0.01) but failed to do so when hyperglycemia resulted from insulin deficiency in IDDM. We conclude that 1) the contribution of glucose to the estimated rate of glutamine de novo synthesis does not increase when elevation of plasma glucose results from insulin deficiency, and 2) the transfer of carbon from glucose to glutamine may depend on insulin availability.