title: Effects of pioglitazone and metformin on intracellular lipid content in liver and skeletal muscle of individuals with type 2 diabetes mellitus.
abstract: Both ectopic fat accumulation and changes of the amount of several adipocyte secreting proteins (adipokines) are thought to contribute to the development of insulin resistance associated with obesity and type 2 diabetes mellitus. We have now investigated the effects of 2 insulin-sensitizing drugs, pioglitazone and metformin, on body fat composition and serum adipokine concentrations in individuals with type 2 diabetes mellitus. A total of 41 diabetic patients were treated with pioglitazone (n =21) or metformin (n =20) for 6 months. Intramyocellular lipid content (IMCL) and hepatic lipid content as well as the areas of subcutaneous and visceral fat deposits in the abdomen were determined by nuclear magnetic resonance spectroscopy before and after drug treatment. The serum concentrations of adiponectin and retinol binding protein 4 were also determined by enzyme-linked immunosorbent assays. Pioglitazone treatment reduced both hepatic lipid content (12.0 +/- 6.1 vs 8.4 +/- 3.7 arbitrary units [AU], P < .01) and IMCL (8.4 +/- 3.6 vs 6.3 +/- 2.4 AU/creatine, P < .01), whereas metformin reduced only IMCL (7.0 +/- 3.6 vs 5.8 +/- 2.0 AU/creatine, P < .05). Although the areas of visceral and subcutaneous fat were not significantly affected by treatment with either drug, pioglitazone induced a significant reduction in the ratio of visceral to subcutaneous fat area (0.92 +/- 0.41 vs 0.85 +/- 0.41, P < .05). Pioglitazone treatment also resulted in a marked increase in serum adiponectin concentration (5.6 +/- 4.1 vs 16.2 +/- 9.9 microg/mL, P < .0001) and a small but significant decrease in serum retinol binding protein 4 concentration (73.4 +/- 25.1 vs 65.1 +/- 23.7 microg/mL, P < .05). These results suggest that pioglitazone may improve insulin sensitivity both by affecting serum adipokine concentrations and by reducing the intracellular triglyceride content of liver and skeletal muscle in individuals with type 2 diabetes mellitus.
authors: Department of Clinical Molecular Medicine, Division of Diabetes and Digestive and Kidney Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors: Tetsuya
authors: T
authors: Teranishi
authors: Takeshi
authors: T
authors: Ohara
authors: Kengo
authors: K
authors: Maeda
authors: Masako
authors: M
authors: Zenibayashi
authors: Kunichi
authors: K
authors: Kouyama
authors: Yushi
authors: Y
authors: Hirota
authors: Hideaki
authors: H
authors: Kawamitsu
authors: Masahiko
authors: M
authors: Fujii
authors: Kazuro
authors: K
authors: Sugimura
authors: Masato
authors: M
authors: Kasuga
mesh_terms: D050153:Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D000077205:Pioglitazone; D012177:Retinol-Binding Proteins / Q000378:metabolism; D054839:Retinol-Binding Proteins, Plasma; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; C101326:RBP4 protein, human; D012177:Retinol-Binding Proteins; D054839:Retinol-Binding Proteins, Plasma; D045162:Thiazolidinediones; D008687:Metformin; D000077205:Pioglitazone