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Effects of glipizide on glucose metabolism and muscle content of the insulin-regulatable glucose transporter (GLUT 4) and glycogen synthase activity during hyperglycaemia in type 2 diabetic patients

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Abstract

To examine whether sulphonylureas influence hyperglycaemia-induced glucose disposal and suppression of hepatic glucose production (HGP) in type 2 diabetes mellitus, a 150-min hyperglycaemic (plasma glucose 14 mmol/l) clamp with concomitant somatostatin infusion was used in eight type 2 diabetic patients before and after 6 weeks of glipizide (GZ) therapy. During the clamp a small replacement dose of insulin was given (0.15 mU/kg per min). Isotopically determined glucose-induced glucose uptake was similar before and after GZ administration which led to improved glycaemic control (basal plasma glucose 12.2±1.3 vs 8.9±0.7 mmol/l;P<0.01). Glucose-induced suppression of HGP was, however, more pronounced during GZ treatment (0.96±0.14 vs 1.44±0.20 mg/kg per min;P<0.02). Following GZ treatment hyperglycaemia failed to stimulate glycogen synthase activity. Moreover, GZ resulted in a significant increase in the immunoreactive abundance of the insulin-regulatable glucose transport protein (GLUT 4) (P<0.02). In conclusion, these results suggest that GZ therapy in type 2 diabetic patients enhances hepatic sensitivity to hyperglycaemia, while glucose-induced glucose uptake remains unaffected. In addition, GZ tends to normalize the activity of glycogen synthase and increases the content of GLUT 4 protein in skeletal muscle.

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Authors and Affiliations

  1. Medical Department M (Endocrinology and Diabetes), Aarhus Kommunehospital, DK-8000, Aarhus C, Denmark

    O. Schmitz, S. Lund, L. Ørskov, N. Møller, O. Rasmussen & J. S. Christiansen

  2. Department of Medicine C, Aarhus Amtssygehus, Aarhus, Denmark

    J. F. Bak & P. H. Andersen

  3. Steno Diabetes Center, Copenhagen, Denmark

    O. Pedersen

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  1. O. Schmitz
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  2. S. Lund
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  3. J. F. Bak
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  4. L. Ørskov
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  5. P. H. Andersen
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  6. N. Møller
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  7. O. Rasmussen
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  8. J. S. Christiansen
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  9. O. Pedersen
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Schmitz, O., Lund, S., Bak, J.F. et al. Effects of glipizide on glucose metabolism and muscle content of the insulin-regulatable glucose transporter (GLUT 4) and glycogen synthase activity during hyperglycaemia in type 2 diabetic patients. Acta Diabetol 31, 31–36 (1994). https://doi.org/10.1007/BF00580757

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  • DOI: https://doi.org/10.1007/BF00580757

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