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Sulphonylurea stimulates glucose uptake in rats through an ATP-sensitive K+ channel dependent mechanism

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We studied the effect of gliclazide, a second-generation sulphonylurea, on rat skeletal muscle glucose uptake using perfused hindquarter muscle preparations. Gliclazide at concentrations of 10 to 1000 Μg/ml increased (p<0.05) the basal glucose uptake. The effect of gliclazide on glucose uptake was immediate and dose-dependent, reaching a plateau at a concentration of 300 Μg/ml; the half-maximal effect was obtained between 25 and 50 Μg/ml. The glucose uptake stimulated by gliclazide (300–1000 Μg/ ml) did not differ from that achieved by 10−9 mol/l insulin, and was lower (p<0.05) than that obtained with 10−7 mol/l insulin. The combination of gliclazide (300 Μg/ml) and 10−9 mol/l insulin produced an increase in glucose uptake (7.7±0.6 Μmol · g−1 · h−1, n=8, mean±SEM) which was higher (p<0.05) than that achieved with 10−9 mol/l insulin (5.6±0.7 Μmol · g−1 · h−1, n=11) and not different from that obtained with 10−7 mol/l insulin (9.8±1.0 Μmol · g−1 · h−1, n=11). Diazoxide (100 Μmol/l), an ATP-sensitive K+ channel opener, reversed the stimulatory effect of gliclazide (100 Μg/ml) on muscle glucose uptake from 3.1±0.4 to 0.5±0.2 Μmol · g−1 · h−1, (n=7, p<0.001). The addition of diazoxide prior to gliclazide into the perfusion medium blocked the gliclazide-induced glucose uptake by the hindquarter muscle preparations. In conclusion, gliclazide alone has an immediate stimulatory effect on glucose uptake by skeletal muscle and together with insulin has an additive effect on muscle glucose uptake. The effect of gliclazide on muscle glucose uptake seems to be due to the inhibition of ATP-sensitive K+ channels.

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Non-insulin-dependent diabetes mellitus


glucose transporter


  1. 1.

    Henquin JC (1988) ATP-sensitive K+ channels may control glucose-induced electrical activity in pancreatic Β-cells. Biochem Biophys Res Commum 156: 769–775

  2. 2.

    Best JD, Judzewitsch RG, Pfeifer MA, Beard JC, Halter JB, Porte D Jr (1982) The effect of chronic sulfonylurea therapy on hepatic glucose production in non-insulin dependent diabetes. Diabetes 31: 333–338

  3. 3.

    Kolterman OG, Gray RS, Shapiro G, Scarlett JA, Griffin J, Olefsky JM (1984) The acute and chronic effects of sulfonylurea therapy in type II diabetic subjects. Diabetes 33: 346–354

  4. 4.

    Simonson DC, Ferrannini E, Bevilacqua S et al. (1984) Mechanism of improvement in glucose metabolism after chronic glyburide therapy. Diabetes 33: 838–845

  5. 5.

    DeFronzo RA, Jacot E, Jequier E, Maeder E, Felber JP (1981) The effect of insulin on the disposal of intravenous glucose: results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes 30: 1000–1007

  6. 6.

    Feldman JM, Lebovitz HE, Durham NC (1969) An insulin dependent effect of chronic tolbutamide administration on the skeletal muscle carbohydrate transport system. Diabetes 18: 84–95

  7. 7.

    Wang PH, Beguinot F, Smith RJ (1987) Augmentation of the effects of insulin and insulin-like growth factors I and II on glucose uptake in cultured rat skeletal muscle cells by sulfonylureas. Diabetologia 30: 797–803

  8. 8.

    Wang PH, Moller D, Flier JS, Nayak RC, Smith RJ (1989) Coordinate regulation of glucose transporter function, number and gene expression by insulin and sulfonylureas in L6 rat skeletal muscle cells. J Clin Invest 84: 62–67

  9. 9.

    Daniels EL, Lewis SB (1982) Acute tolbutamide administration alone or combined with insulin enhances glucose uptake in the perfused rat hindlimb. Endocrinology 110: 1840–1842

  10. 10.

    Kramer JH, Lampson WG, Schaffer SW (1983) Effect of tolbutamide on myocardial energy metabolism. Am J Physiol 245: H313–H319

  11. 11.

    Ruderman NB, Houghton CRS, Hems R (1971) Evaluation of the isolated perfused rat hindquarter for the study of muscle metabolism. Biochem J 124: 639–651

  12. 12.

    Dohm GL, Kasperek GJ, Tapscott EB, Beecher GR (1980) Effect of exercise on synthesis and degradation of muscle protein. Biochem J 188: 255–262

  13. 13.

    Davidson MB, Molnar G, Furman A, Yamaguchi D (1991) Glyburide-stimulated glucose transport in cultured muscle cells via protein kinase C-mediated pathway requiring new protein synthesis. Diabetes 40: 1531–1538

  14. 14.

    Rogers BJ, Standaert ML, Pollet RJ (1987) Direct effects of sulfonylurea agents on glucose transport in the BC3H-1 myocyte. Diabetes 36: 1292–1296

  15. 15.

    Tordjman KM, Leingang KA, James DE, Mueckler MM (1989) Differential regulation of two distinct glucose transporter species expressed in 3T3-L1 adipocytes: effects of chronic insulin and tolbutamide treatment. Proc Natl Acad Sci USA 86: 7761–7765

  16. 16.

    Campbell DB, Taylor A, Taylor D, Gordon B, Ings RMJ (1987) The biodisposition and pharmacodynamics of gliclazide in man. In: Halim D, Nielsen SP (eds) Proceedings from a Danish-Dutch meeting on diabetes mellitus, Copenhagen, November 2 1985. FADL Publishers, Copenhagen, Aarhus, Odense, pp 24–38

  17. 17.

    Chiasson JL, Dietz MR, Shikama H, Wootten M, Exton JH (1980) Insulin regulation of skeletal muscle glycogen metabolism. Am J Physiol 239: E69–E74

  18. 18.

    Lewis SB, Shultz TA, Westbie DK, Gerich JE, Wallin JD (1977) Insulin-glucose dynamics during flow-through perfusion of the isolated rat hindlimb. Horm Metab Res 9: 190–195

  19. 19.

    Greenfield MS, Doberne L, Rosenthal M, Schulz B, Widstrom A, Reaven GM (1982) Effect of sulfonylurea treatment on in vivo insulin secretion and action in patients with non-insulin dependent diabetes mellitus. Diabetes 31: 307–312

  20. 20.

    Bak JF, Schmitz O, Sorensen NS, Pedersen O (1989) Postreceptor effects of sulfonylurea on skeletal muscle glycogen synthase activity in type II diabetic patients. Diabetes 38: 1343–1350

  21. 21.

    Bolinder J, östman J, Arner P (1985) Reversal of insulin resistance in adipose tissue of non-insulin-dependent diabetics by treatment with diet and sulfonylurea. Acta Endocrinol (Copenh) 108: 85–90

  22. 22.

    Jacobs DB, Jung CY (1985) Sulfonylurea potentiates insulin-induced recruitment of glucose transport carrier in rat adipocytes. J Biol Chem 260: 2593–2596

  23. 23.

    Altan N, Altan VM, Mikolay L, Larner J, Schwartz CFW (1985) Insulin-like and insulin-enhancing effects of the sulfonylurea glyburide on rat adipose glycogen synthase. Diabetes 34: 281–286

  24. 24.

    Muller M, Wied S (1993) The sulfonylurea drug, glimepiride, stimulates glucose transport, glucose transporter translocation, and dephosphorylation in insulin-resistant rat adipocytes in vitro. Diabetes 42: 1852–1867

  25. 25.

    Thirlwell MP, Zsoter T (1972) The effect of diazoxide on the veins. Am Heart J 83: 512–517

  26. 26.

    Gopalakrishnan M, Johnson DE, Janis RA, Triggle D (1991) Characterization of binding of the ATP-sensitive potassium channel ligand, [3H]glyburide, to neuronal and muscle preparations. J Pharmacol Exp Ther 257: 1162–1171

  27. 27.

    Bray KM, Quast U (1992) A specific binding site for K+ channel openers in rat aorta. J Biol Chem 267: 11689–11692

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Correspondence to A. Rovira.

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Pulido, N., Casla, A., Suárez, A. et al. Sulphonylurea stimulates glucose uptake in rats through an ATP-sensitive K+ channel dependent mechanism. Diabetologia 39, 22–27 (1996).

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Key words

  • Gliclazide
  • skeletal muscle
  • glucose uptake
  • hindquarter perfusion
  • insulin
  • ATP-sensitive
  • K+ channels
  • diazoxide