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Publication
Adipocyte JAK2 mediated growth hormone-induced hepatic insulin resistance
Authors Corbit KC, Camporez JP, Tran JL, Wilson CG, Lowe DA, Nordstrom SM, Ganeshan K,
Perry RJ, Shulman GI, Jurczak MJ, Weiss EJ
Submitted By Michael Jurczak on 2/28/2017
Status In press
Journal JCI insight
Year 2017
Date Published 2/9/2017
Volume : Pages 2(3) : Not Specified
PubMed Reference 28194444
Abstract For nearly 100 years, growth hormone (GH) has been known to affect insulin
sensitivity and risk of diabetes. However, the tissue governing the effects of
GH signaling on insulin and glucose homeostasis remains unknown. Excess GH
reduces fat mass and insulin sensitivity. Conversely, GH insensitivity (GHI) is
associated with increased adiposity, augmented insulin sensitivity, and
protection from diabetes. Here, we induce adipocyte-specific GHI through
conditional deletion of Jak2 (JAK2A), an obligate transducer of GH signaling.
Similar to whole-body GHI, JAK2A mice had increased adiposity and extreme
insulin sensitivity. Loss of adipocyte Jak2 augmented hepatic insulin
sensitivity and conferred resistance to diet-induced metabolic stress without
overt changes in circulating fatty acids. While GH injections induced hepatic
insulin resistance in control mice, the diabetogenic action was absent in JAK2A
mice. Adipocyte GH signaling directly impinged on both adipose and hepatic
insulin signal transduction. Collectively, our results show that adipose tissue
governs the effects of GH on insulin and glucose homeostasis. Further, we show
that JAK2 mediates liver insulin sensitivity via an extrahepatic, adipose
tissue-dependent mechanism.




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