Role of skeletal muscle in thiazolidinedione insulin sensitizer (PPARgamma agonist) action.
| Title: | Role of skeletal muscle in thiazolidinedione insulin sensitizer (PPARgamma agonist) action. |
|---|---|
| Authors: | Zierath JR; Department of Clinical Biochemistry, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.; Ryder JW; Doebber T; Woods J; Wu M; Ventre J; Li Z; McCrary C; Berger J; Zhang B; Moller DE |
| Source: | Endocrinology [Endocrinology] 1998 Dec; Vol. 139 (12), pp. 5034-41. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375040 Publication Model: Print Cited Medium: Print ISSN: 0013-7227 (Print) Linking ISSN: 00137227 NLM ISO Abbreviation: Endocrinology Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2017- : New York : Oxford University Press; Original Publication: Los Angeles, Calif. : Association for the Study of Internal Secretions |
| MeSH Terms: | Thiazolidinediones*; Hypoglycemic Agents/*pharmacology ; Insulin Resistance/*physiology ; Muscle, Skeletal/*physiology ; Receptors, Cytoplasmic and Nuclear/*agonists ; Thiazoles/*pharmacology ; Transcription Factors/*agonists; Deoxyglucose/pharmacokinetics ; Insulin/pharmacology ; Mice/genetics ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Myocardium/metabolism ; Obesity/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism ; Transcription Factors/metabolism ; Animals ; Humans ; In Vitro Techniques ; Male ; Rats ; Rats, Sprague-Dawley ; Rats, Zucker |
| Abstract: | Thiazolidinedione (TZD) insulin sensitizers are specific agonists of peroxisome proliferator activated receptor (PPAR)gamma. However, their mechanism of action and the in vivo target tissue(s) that mediate insulin sensitization remain poorly defined. Although PPARgamma messenger RNA expression has been reported in skeletal muscle, the expression of PPARgamma within myocytes in intact muscle tissue has not been examined. An antipeptide PPARgamma antibody was generated; immunohistochemistry was then used to demonstrate that PPARgamma is present within nuclei of myocytes [in both skeletal (white and red fibers) and cardiac tissue (rodent and human)]. The effect of insulin sensitizer treatment on muscle insulin action was studied using ob/ob mice after 4 days dosing with a potent (6 nM PPARgamma Kd) TZD (10 mg/kg x day). 2-deoxyglucose (2-DOG) uptake was then assessed in freshly isolated soleus muscles from lean vs. ob/ob vs. TZD-treated ob/ob mice. In lean mouse muscles, 2-DOG uptake was stimulated by 82%, 95%, 165% (with 25, 100, 2000 microU/ml insulin); muscles from ob/ob were severely insulin resistant ( |
| Substance Nomenclature: | 0 (Hypoglycemic Agents); 0 (Insulin); 0 (Receptors, Cytoplasmic and Nuclear); 0 (Thiazoles); 0 (Thiazolidinediones); 0 (Transcription Factors); 103788-05-2 (AD 5075); 9G2MP84A8W (Deoxyglucose) |
| Entry Date(s): | Date Created: 19981201 Date Completed: 19981224 Latest Revision: 20141120 |
| Update Code: | 20260130 |
| DOI: | 10.1210/endo.139.12.6364 |
| PMID: | 9832442 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't