Thyroid-stimulating hormone improves insulin sensitivity in skeletal muscle cells via cAMP/PKA/CREB pathway-dependent upregulation of insulin receptor substrate-1 expression

Autor: Geun Hyung Kang, Ye An Kim, Kyong Soo Park, Sun Wook Cho, Min Kyong Moon, Byung-Chul Oh, Sun Kyoung Han, Young Do Koo, Do Joon Park, Young Joo Park, Sung Soo Chung, Hwan Hee Kim
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
endocrine system
medicine.medical_specialty
endocrine system diseases
Insulin Receptor Substrate Proteins
Thyrotropin
030209 endocrinology & metabolism
Diet
High-Fat
Biochemistry
03 medical and health sciences
0302 clinical medicine
Endocrinology
Insulin resistance
Downregulation and upregulation
Internal medicine
Insulin receptor substrate
medicine
Animals
Insulin
Cyclic AMP Response Element-Binding Protein
Muscle
Skeletal
Promoter Regions
Genetic
Molecular Biology
Insulin-like growth factor 1 receptor
biology
Base Sequence
Body Weight
Skeletal muscle
Biological Transport
Glucose Tolerance Test
medicine.disease
Cyclic AMP-Dependent Protein Kinases
IRS1
Rats
Up-Regulation
Mice
Inbred C57BL
Insulin receptor
030104 developmental biology
medicine.anatomical_structure
Cholesterol
Glucose
biology.protein
Insulin Resistance
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
Zdroj: Molecular and cellular endocrinology. 436
ISSN: 1872-8057
Popis: Thyroid-stimulating hormone (TSH) receptor is expressed in extrathyroidal tissues such as hepatocytes, adipocytes, and skeletal muscle, which suggests a possible novel role of TSH in various metabolic processes in extrathyroidal tissues independent of thyroid hormones. We investigated whether TSH has any effects on glucose tolerance and insulin sensitivity in the skeletal muscle using diet-induced obesity (DIO) mouse models and rodent skeletal muscle cells. TSH improved glucose tolerance in DIO mice and this was associated with an improvement of skeletal muscle insulin sensitivity resulting from the increased expression of insulin receptor substrate (IRS)-1 protein and mRNA therein. TSH significantly increased both basal and insulin-stimulated glucose transport in rat L6 myotubes and increased the expression of IRS-1 protein and mRNA in these cells as well. TSH also stimulated Irs1 promoter activation; this stimulation was abolished by protein kinase A (PKA) inhibition using H89 or by mutation of the cAMP-response element site located at -1155 to -875 bp of the Irs1 promoter region, supporting a novel role of TSH activated-cAMP/PKA/CREB signaling in the regulation of Irs1 expression. In conclusion, TSH improves insulin sensitivity in skeletal muscle by increasing Irs1 gene expression. This regulatory effect is mediated by a PKA-CREB-dependent pathway.
Databáze: OpenAIRE
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