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Salt‐inducible kinase 1 links p300 phosphorylation to CREB regulated gluconeogenesis post burn
Author(s) -
Brooks Natasha C,
Smith Alexandra H,
Hiyama Yaeko,
Finnerty Celeste C,
Herndon David N,
Boehning Darren,
Jeschke Marc G
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.758.7
Subject(s) - creb , gluconeogenesis , catecholamine , propranolol , endocrinology , medicine , activator (genetics) , kinase , chemistry , biology , receptor , transcription factor , gene , biochemistry , metabolism
Severe burn injury results in sustained catecholamine release and increased cyclic AMP (cAMP) levels. cAMP‐induced inhibition of salt‐inducible kinase 1 (SIK1) has been shown to promote recruitment of the transcriptional co‐activator p300 to cAMP response element binding protein (CREB), resulting in gluconeogenesis. Gluconeogenesis is increased and maintained post‐burn injury yet the molecular mechanism is unknown. We hypothesize that catecholamine‐induced inhibition of SIK1 resulting in increased p300 transcriptional activity sustains gluconeogenesis. The 60% total body surface area burn model on rats was employed as a model system. The catecholamine surge during burn injury led to the inhibition of SIK1, increased blood glucose levels, and increased p300 mediated transcription of CREB‐regulated gluconeogenic genes. Restoration of SIK1 activity by administration of propranolol, a non‐selective β1/2 adrenergic receptor antagonist, resulted in inhibition of p300‐ mediated transcription and decreased blood glucose levels. We conclude that catecholamine release after severe burn injury leads to inhibition of SIK1, resulting in sustained gluconeogenesis. This work was supported by grants from Shriners Hospitals for Children and (SHG 8660 and 6840) the National Institute of Health (RO1‐ GM087285‐0182)