| Regulation of glucose transport in cultured muscle cells by novel hypoglycemic agents. | |
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MedLine Citation:
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PMID: 7637655 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The antidiabetic agent troglitazone (CS-045) and a metabolite designated M3 have potent blood glucose-lowering actions. The mechanism of the hypoglycemic effects of troglitazone and M3 was investigated in cultured L6 muscle cells. Short-term (2-hour) exposure of fully differentiated myotubes to troglitazone had no effect on glucose transport activity; M3 exposure caused a modest (50% to 60%) increase in basal and insulin-stimulated transport. Long-term (72-hour) treatment of myotubes with troglitazone resulted in a doubling of glucose transport in the absence of insulin, whereas M3 treatment resulted in a fivefold increase in basal glucose transport. Transport activity in M3-treated myotubes was greater than that seen after short-term insulin treatment. Insulin did not stimulate transport further in long-term M3-treated cells. A similar effect of prolonged exposure to M3 was observed in nondifferentiated myocytes. The agent had no influence on cell growth or the extent of differentiation. Augmentation of basal glucose transport by M3 was slow in onset, requiring 18 to 24 hours before significant effects were observed and 72 hours for full stimulation. M3 action on glucose transport was also dose-dependent, with half-maximal stimulation at 5 micrograms/mL of the agent and full effects at 10 to 20 micrograms/mL. Total membranes were prepared from control and M3-treated L6 myocytes and myotubes, and glucose transporter (GLUT1 and GLUT4) protein levels were measured by Western blotting. GLUT1 content was increased 2.9- +/- 1.3- and 2.8- +/- .2-fold by M3 treatment in myocytes and myotubes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) |
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Authors:
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T P Ciaraldi; K Huber-Knudsen; M Hickman; J M Olefsky |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Metabolism: clinical and experimental Volume: 44 ISSN: 0026-0495 ISO Abbreviation: Metab. Clin. Exp. Publication Date: 1995 Aug |
Date Detail:
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Created Date: 1995-09-12 Completed Date: 1995-09-12 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0375267 Medline TA: Metabolism Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 976-81 Citation Subset: IM |
Affiliation:
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Medical Research Service, San Diego Veterans Affairs Medical Center, CA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Transport / drug effects, physiology Blotting, Western Cell Line Cell Membrane / chemistry, physiology, ultrastructure Chromans / metabolism, pharmacology* Glucose / pharmacokinetics* Glucose Transporter Type 1 Glucose Transporter Type 4 Hypoglycemic Agents / pharmacology* Insulin / blood Mice Monosaccharide Transport Proteins / analysis, metabolism, physiology Muscle Proteins* Muscles / cytology, drug effects*, metabolism Thiazoles / metabolism, pharmacology* Thiazolidinediones* Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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DK-33649/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chromans; 0/Glucose Transporter Type 1; 0/Glucose Transporter Type 4; 0/Hypoglycemic Agents; 0/Monosaccharide Transport Proteins; 0/Muscle Proteins; 0/Slc2a1 protein, mouse; 0/Slc2a4 protein, mouse; 0/Thiazoles; 0/Thiazolidinediones; 11061-68-0/Insulin; 50-99-7/Glucose; 97322-87-7/troglitazone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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