Role of glucose in the regulation of glutamine metabolism in health and intype 1 insulin-dependent diabetes

To determine the effect of glucose availability on glutamine metabolism, gl utamine kinetics were assessed under conditions of hyperglycemia resulting from 1) intravenous infusion of 7.5% dextrose in healthy adults and 2) insu lin deficiency in young adults with insulin-dependent diabetes mellitus (ID DM). Eight healthy adults and five young adults with IDDM were studied in t he postabsorptive state by use of a primed continuous infusion of D-[U-C-14 ] glucose, L-[5,5,5-H-2(3)]leucine, and L-[3,4-C-13] glutamine. Whether res ulting from insulin deficiency or dextrose infusion, the rise in plasma glu cose was associated with increased glucose turnover (23.5 +/- 0.7 vs. 12.9 +/- 0.3 mu mol.kg(-1).min(-1), P< 0.01 and 20.9 +/- 2.5 vs. 12.8 +/- 0.4 mu mol.kg(-1).min(-1), P = 0.03, in health and IDDM, respectively). In both c ases, high blood glucose failed to alter glutamine appearance rate (Ra) int o plasma [298 +/- 9 vs. 312 +/- 14 mu mol.kg(-1).h(-1), not significant (NS ) and 309 +/- 23 vs 296 +/- 26 mu mol.kg(-1).h(-1), NS, in health and IDDM, respectively] and the estimated fraction of glutamine Ra arising from de n ovo synthesis (210 +/- 7 vs. 217 +/- 10 mu mol.kg(-1).h(-1), NS and 210 +/- 16 vs. 207 +/- 21 mu mol.kg(-1). h(-1), NS, in health and IDDM, respective ly). When compared with the euglycemic day, the apparent contribution of gl ucose to glutamine carbon skeleton increased when high plasma glucose resul ted 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 fr om insulin deficiency in IDDM. We conclude that 1) the contribution of gluc ose to the estimated rate of glutamine de novo synthesis does not increase when elevation of plasma glucose results from insulin deficiency, and 2) th e transfer of carbon from glucose to glutamine may depend on insulin availa bility.