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Publication : Thyroid stimulating hormone increases hepatic gluconeogenesis via CRTC2.

First Author  Li Y Year  2017
Journal  Mol Cell Endocrinol Volume  446
Pages  70-80 PubMed ID  28212844
Mgi Jnum  J:248725 Mgi Id  MGI:6095401
Doi  10.1016/j.mce.2017.02.015 Citation  Li Y, et al. (2017) Thyroid stimulating hormone increases hepatic gluconeogenesis via CRTC2. Mol Cell Endocrinol 446:70-80
abstractText  Epidemiological evidence indicates that thyroid stimulating hormone (TSH) is positively correlated with abnormal glucose levels. We previously reported that TSH has direct effects on gluconeogenesis. However, the underlying molecular mechanism remains unclear. In this study, we observed increased fasting blood glucose and glucose production in a mouse model of subclinical hypothyroidism (only elevated TSH levels). TSH acts via the classical cAMP/PKA pathway and CRTC2 regulates glucose homeostasis. Thus, we explore whether CRTC2 is involved in the process of TSH-induced gluconeogenesis. We show that TSH increases CRTC2 expression via the TSHR/cAMP/PKA pathway, which in turn upregulates hepatic gluconeogenic genes. Furthermore, TSH stimulates CRTC2 dephosphorylation and upregulates p-CREB (Ser133) in HepG2 cells. Silencing CRTC2 and CREB decreases the effect of TSH on PEPCK-luciferase, the rate-limiting enzyme of gluconeogenesis. Finally, the deletion of TSHR reduces the levels of the CRTC2:CREB complex in mouse livers. This study demonstrates that TSH activates CRTC2 via the TSHR/cAMP/PKA pathway, leading to the formation of a CRTC2:CREB complex and increases hepatic gluconeogenesis.
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