title: Effect of triiodothyronine on muscle cell differentiation and blood glucose level in hyperglycemic KK mice.
abstract: KK mice are genetically diabetic animals, showing glucose intolerance and insulin resistance. We examined the effects of 3,3',5-triiodo-L-thyronine (T3) on the blood glucose level and on mRNA levels of muscle cell differentiation markers in hyperglycemic KK mice. T3 treatment (T1, 1 mg; T3, 3 mg; T10, 10 mg/kg/day) of KK mice for 4 days caused a decrease in blood glucose level by 11%, 25%, and 24%, respectively, without affecting body weight. Skeletal muscle of mice treated with T3 (T10) showed a 98% increase in the mRNA level of the glucose transporter isotype 4 (Glut4). In contrast, T3 treatment did not affect the mRNA level of the isotype 1 (Glut1) transporter. The mRNA level of a muscle cell specific differentiation marker, MyoD, showed a significant increase in the T3 treatment group with an accompanying enhancement of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA level. These results suggest that T3 stimulates muscle cell differentiation in vivo, concomitant with a stimulation of cellular glucose metabolism, thus decreasing the blood glucose level in hyperglycemic KK mice.
authors.affiliation: Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan. simokawa@yamanouchi.co.jp
authors.forename: T
authors.initials: T
authors.lastname: Shimokawa
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Shioduka
authors.forename: J
authors.initials: J
authors.lastname: Irie
authors.forename: O
authors.initials: O
authors.lastname: Ezaki
mesh_terms: D000818:Animals; D015415:Biomarkers; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D051275:Glucose Transporter Type 4; D006943:Hyperglycemia / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D017570:MyoD Protein / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D017570:MyoD Protein; D012333:RNA, Messenger; C495693:Slc2a4 protein, mouse; D014284:Triiodothyronine