Troglitazone regulation of glucose metabolism in human skeletal muscle cultures from obese type II diabetic subjects

• Published in: The journal of clinical endocrinology and metabolism Vol. 83; no. 5; pp. 1636 - 1643
• Main Authors: PARK, K. S, CIARALDI, T. P, ABRAMS-CARTER, L, MUDALIAR, S, NIKOULINA, S. E, HENRY, R. R
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.05.1998
• Subjects: Adult; Biological and medical sciences; Cells, Cultured; Chromans - administration & dosage; Chromans - pharmacology; Diabetes Mellitus - metabolism; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glucose - metabolism; Glucose Transporter Type 1; Glycogen Synthase - metabolism; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - pharmacology; Insulin - pharmacology; Medical sciences; Middle Aged; Monosaccharide Transport Proteins - genetics; Monosaccharide Transport Proteins - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Obesity; RNA, Messenger - metabolism; Thiazoles - administration & dosage; Thiazoles - pharmacology; Thiazolidinediones; Endocrinopathy; Human; Cell culture; Obesity; Energy metabolism; Nutrition disorder; Glucose; Striated muscle; Metabolism; Non insulin dependent diabetes; Biological activity; Chemotherapy; Treatment; Nutritional status; Troglitazone
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.83.5.1636

To determine the effects of troglitazone on abnormal skeletal muscle glucose metabolism, muscle cultures from type II diabetic patients were grown for 4-6 weeks and then fused for 4 days either without or with troglitazone (1-5 micrograms/mL; chronic studies) or had troglitazone added for 90 min (1-5 micrograms/mL) at completion of fusion (acute studies). Acute troglitazone treatment stimulated glucose uptake, but not glycogen synthase (GS) activity 2-fold (P < 0.05) in a dose-dependent fashion and to the same extent as the addition of maximal (33 nmol/L) insulin. Maximal chronic troglitazone (5 micrograms/mL for 4 days) increased both glucose uptake (from 9.0 +/- 1.5 to 40.9 +/- 8.1 pmol/mg protein.min; P < 0.05) and GS fractional velocity (from 5.4 +/- 0.7% to 20.6 +/- 6.3%; P < 0.05) by approximately 4-fold. At each concentration of chronic troglitazone, glucose uptake rates were similar in the absence and presence of maximal (33 nmol/L) insulin concentrations. In contrast, insulin-stimulated GS activity was greater (P < 0.05) when maximal chronic troglitazone and acute insulin were combined than when chronic troglitazone alone was used. After 4 days of troglitazone, GLUT1 messenger ribonucleic acid and protein increased about 2-fold (P < 0.05) without a change in GLUT4 or GS messenger ribonucleic acid and protein. We conclude that troglitazone has both acute and chronic effects to improve skeletal muscle glucose metabolism of obese type II diabetic subjects. These effects involve direct insulin mimetic stimulatory actions as well as indirect insulin-sensitizing properties.