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Determination and kinetic analysis of non-insulin mediated glucose uptake in Type 1 (insulin-dependent) diabetes mellitus

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In man, total glucose uptake is the sum of insulin mediated glucose uptake and non-insulin mediated glucose uptake. The latter pathway has not been examined in Type 1 (insulin-dependent) diabetes mellitus. In order to assess non-insulin mediated glucose uptake in Type 1 diabetes, we measured steady-state rates of glucose uptake during glucose clamps at 5.27, 9.71 and 12.5 mmol/l using low (0.25 mU· kg−1·min−1), intermediate (0.75 mU·kg−1·min−1) and high (1.50 mU·kg−1·min−1) insulin infusion rates in 10 subjects with Type 1 diabetes. For insulin infusion rates of 0.25, 0.75 and 1.50 mU·kg−1·min−1 as plasma glucose rose from 5.27 to 9.71 mmol/l, total glucose uptake increased by 35, 43 and 52 percent respectively (p<0.05 for each insulin infusion rate). For all three insulin infusion rates, there was no significant increase in total glucose uptake as plasma glucose increased from 9.71 to 12.5 mmol/l. At each glycaemic level, glucose uptake correlated significantly with plasma free insulin (r=0.81, p<0.01 at 5.71 mmol/l; r=0.84, p<0.01 at 9.71 mmol/l; r=0.73, p<0.02 at 12.5 mmol/l). Linear regression analysis to a point corresponding to plasma free insulin equalling zero, yielded values for non-insulin mediated glucose uptake (mmol·kg−1·min−1) of 0.11,0.14,0.18 at plasma glucose of 5.27, 9.7 and 12.5 mmol/l respectively. Thus, increasing plasma glucose concentrations were associated with increasing rates of non-insulin mediated glucose uptake. For each insulin infusion rate used, the percent of total glucose uptake accounted for by non-insulin mediated glucose uptake remained independent of plasma glucose concentration, but decreased as insulin infusion rate increased. During the insulin infusion at 0.25 mU·kg−1·min−1, this percentage ranged from 83.7 to 91.4%. Analysis of glucose uptake data derived for theoretical plasma insulin levels of 0, 40, 80 and 160 μU/ml yielded linear Eadie-Hofstee plots (r=− 0.83 to − 0.99), suggesting that insulin increased Vmax but did not alter Km. Hence, in these subjects with Type 1 diabetes, glucose uptake, both insulin mediated and non-insulin mediated can be described by Michaelis-Menten kinetics. Comparison of values obtained for Vmax and Km in the present studies of Type 1 diabetes with those obtained from non-diabetic subjects indicates that non-insulin dependent glucose uptake in Type 1 diabetes is quantitatively similar to that of non-diabetic subjects.


  1. 1.

    Bergman RN, Finegood DT, Ader M (1985) Assessment of insulin sensitivity in vivo. Endocr Rev 6: 45–86

  2. 2.

    Gottesman I, Mandarino L, Gerich J (1983) Estimation and kinetic analysis of insulin-independent glucose uptake in human subjects. Am J Physiol 244: E632-T635

  3. 3.

    Baron AD, Kolterman OG, Bell J, Mandarino LJ, Olefsky JM (1985) Rates of noninsulin-mediated glucose uptake are elevated in type II diabetic subjects. J Clin Invest 76: 1782–1788

  4. 4.

    Gottesman I, Mandarino L, Gerich J (1984) Use of glucose uptake and glucose clearance for the evaluation of insulin action in vivo. Diabetes 33: 184–191

  5. 5.

    DeFronzo RA, Hendler R, Simonson D (1982) Insulin resistance is a prominent feature of insulin-dependent diabetes. Diabetes 31: 795–801

  6. 6.

    Yki-Jarvinen H, Koivisto VA (1986) Natural course of insulin resistance in type I diabetes. N Engl J Med 315: 224–230

  7. 7.

    National Diabetes Data Group (1979) Classification and diagnosis of diabetes mellitus and other categories of glucose tolerance. Diabetes 28: 1039–1057

  8. 8.

    White NH, Skor D, Santiago JV (1982) Practical closed-loop insulin delivery. Ann Int Med 97: 210–213

  9. 9.

    Rizza R, Mandarino L, Gerich J (1981) Dose-response characteristics for the effect of insulin on production and utilization of glucose in man. Am J Physiol 240: E630-E639

  10. 10.

    Sherwin RS, Kramer KJ, Tobin JD, Insel PA, Liljen Quist JE, Berman M, Andres R (1974) A model of the kinetics of insulin in man. J Clin Invest 53: 1481–1492

  11. 11.

    McGuire E, Helderman J, Tobin J, Andres R, Berman M (1976) Effects of arterial versus venous sampling on analysis of glucose kinetics in man. J Appl Physiol 41: 565–573

  12. 12.

    Desbuquois B, Auerbach GD (1971) Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. J Clin Endocrinol Metab 33: 732–738

  13. 13.

    Hanna AK, Zinman B, Nakhooda AF, Minuk HL, Stokes EF, Albisser AM, Leibel BS, Marliss EB (1980) Insulin, glucagon and aminoacids during glycemic control by the artificial pancreas in diabetic man. Metabolism 29: 321–332

  14. 14.

    Rizza R, Mandarino L, Gerich J (1981) Mechanism and significance of insulin resistance in noninsulin-dependent diabetes mellitus. Diabetes 30: 990–995

  15. 15.

    DeBodo R, Steele R, Alstszuler N, Dunn A, Bishop J (1963) On the hormonal regulation of carbohydrate metabolism: studies with C14-glucose. Recent Prog Res 19: 445–488

  16. 16.

    Dunn A, Katz J, Golden S, Chenoweth M (1976) Estimation of glucose turnover and recycling in rabbits using various [3H14C] glucose labels. Am J Physiol 230: 1159–1162

  17. 17.

    Radziuk J, Norwich KH, Vranic M (1978) Experimental validation of measurements of glucose turnover in nonsteady state. Am J Physiol 234: E84-E93

  18. 18.

    Cushman S, Wardzala L (1980) Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane. J Biol Chem 255: 4758–4762

  19. 19.

    Karnielli E, Hissin P, Simpson I, Salans L, Cushman S (1981) A possible mechanism of insulin resistance in the rat adipose cell in streptozotocin-induced diabetes mellitus. J Clin Invest 68: 811–814

  20. 20.

    Gottesman I, Mandarino L, Verdonk C, Rizza R, Gerich J (1982) Insulin increases the maximum velocity for glucose uptake without altering the Michaelis constant in man. J Clin Invest 70: 1310–1314

  21. 21.

    Best JD, Taborsky GJ Jr, Halter JB, Porte D Jr (1981) Glucose disposal is not proportional to plasma glucose level in man. Diabetes 30: 847–850

  22. 22.

    Ciaraldi T, Kolterman O, Siegal J, Olefsky J (1979) Insulin-stimulated glucose transport in human adipocytes. Am J Physiol 236: E621-E625

  23. 23.

    LeMarchand-Brustel Y, Freychet P (1979) Effect of fasting and streptozotocin diabetes on insulin binding and action in the isolated mouse soleus muscle. J Clin Invest 64: 1505–1515

  24. 24.

    Berhanu P, Olefsky J (1981) Effects of insulin and insulin-like agents on the glucose transport system of cultured human fibroblasts. Diabetes 30: 523–529

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Shumak, S.L., Gulan, M., Zinman, B. et al. Determination and kinetic analysis of non-insulin mediated glucose uptake in Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 32, 28–33 (1989). https://doi.org/10.1007/BF00265400

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Key words

  • Type 1 (insulin-dependent) diabetes
  • glucose uptake
  • non-insulin mediated glucose uptake
  • glucose kinetics