Intracellular glucose metabolism after long term metabolic control with glyburide: improved glucose oxidation with unchanged glycogen synthase activity
| Autor: | M. Joyce, Robert R. Henry, C. Murata, Barry Gumbiner, Yuh-Min Song, T. M. Ditzler, Kyo-Il Suh |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Glucose uptake Clinical Biochemistry Pyruvate Dehydrogenase Complex Fatty Acids Nonesterified Carbohydrate metabolism Biochemistry Body Mass Index Glibenclamide Endocrinology Internal medicine Glyburide medicine Hyperinsulinemia Humans Insulin Obesity C-Peptide Chemistry Muscles Biochemistry (medical) Calorimetry Indirect Metabolism Middle Aged Glucagon medicine.disease Glucose Glycogen Synthase Diabetes Mellitus Type 2 Basal (medicine) Body Composition Glucose Clamp Technique Female Oxidation-Reduction Hyperinsulinism medicine.drug |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 77:464-470 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem.77.2.8345053 |
| Popis: | To determine whether improved metabolic control with long term glyburide treatment alters intracellular glucose metabolism independent of effects on glucose uptake (GU), we studied eight obese patients with noninsulin-dependent diabetes mellitus before and 7 months after glyburide therapy. Indirect calorimetry and skeletal muscle biopsies were performed in the basal state and during 300 pmol/m2.min insulin infusions, with glucose turnover rates determined by [3-3H]glucose turnover. During the glucose clamps, rates of GU were matched before and after treatment using equivalent hyperinsulinemia and variable levels of hyperglycemia. After glyburide treatment, rates of GU were decreased in the basal state [4.16 +/- 0.57 vs. 3.29 +/- 0.37 mg/kg fat free mass (FFM)/min; P0.05], but similar during glucose clamps (11.53 +/- 1.42 vs. 11.93 +/- 1.32 mg/kg FFM.min; P = NS) according to study design. In both the basal state and during glucose clamps after glyburide therapy, rates of glucose oxidative metabolism (Gox) increased by 68-78% [1.21 +/- 0.16 vs. 2.03 +/- 0.31 mg/kg FFM.min (P0.05) and 3.13 +/- 0.51 vs. 5.58 +/- 0.55 mg/kg FFM.min (P0.05), respectively], and rates of nonoxidative glucose metabolism decreased [2.96 +/- 0.68 vs. 1.25 +/- 0.21 mg/kg FFM.min (P0.05) and 8.40 +/- 1.50 to 6.30 +/- 1.40 mg/kg FFM.min (P0.01), respectively]. Circulating plasma FFA levels and rates of fat oxidation (Fox) remained unchanged in both the basal state and during clamp studies. Skeletal muscle glycogen synthase (GS) activity, expressed as fractional velocity, was unchanged by glyburide therapy (2.2 +/- 0.8 vs. 2.7 +/- 0.3% in the basal state and 7.3 +/- 1.8 vs. 6.1 +/- 0.9% during clamps; both P = NS). In summary, at both matched (during clamp studies) and unmatched (during basal studies) rates of GU, improved metabolic control with glyburide therapy resulted in marked improvement of Gox independent of the effects on GU. The improvement in Gox was not associated with changes in Fox, circulating FFA, or muscle GS activity. These data indicate that long term metabolic control achieved by glyburide therapy markedly improves Gox, but not skeletal muscle GS activity, in noninsulin-dependent diabetes mellitus independent of GU and Fox. |
| Databáze: | OpenAIRE |
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