Effect of triiodothyronine on muscle cell differentiation and blood glucose level in hyperglycemic KK mice.
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.
Shimokawa
T
T
Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan. simokawa@yamanouchi.co.jp
Kato
M
M
Shioduka
K
K
Irie
J
J
Ezaki
O
O
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*
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