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Publication
ARCGHR Neurons Regulate Muscle Glucose Uptake.
Authors de Lima JBM, Debarba LK, Rupp AC, Qi N, Ubah C, Khan M, Didyuk O, Ayyar I, Koch
M, Sandoval DA, Sadagurski M
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Cells
Year 2021
Date Published 5/1/2021
Volume : Pages 10 : Not Specified
PubMed Reference 34063647
Abstract The growth hormone receptor (GHR) is expressed in brain regions that are known
to participate in the regulation of energy homeostasis and glucose metabolism.
We generated a novel transgenic mouse line (GHRcre) to characterize
GHR-expressing neurons specifically in the arcuate nucleus of the hypothalamus
(ARC). Here, we demonstrate that ARCGHR+ neurons are co-localized with
agouti-related peptide (AgRP), growth hormone releasing hormone (GHRH), and
somatostatin neurons, which are activated by GH stimulation. Using the designer
receptors exclusively activated by designer drugs (DREADD) technique to control
the ARCGHR+ neuronal activity, we demonstrate that the activation of ARCGHR+
neurons elevates a respiratory exchange ratio (RER) under both fed and fasted
conditions. However, while the activation of ARCGHR+ promotes feeding, under
fasting conditions, the activation of ARCGHR+ neurons promotes glucose over fat
utilization in the body. This effect was accompanied by significant improvements
in glucose tolerance, and was specific to GHR+ versus GHRH+ neurons. The
activation of ARCGHR+ neurons increased glucose turnover and whole-body
glycolysis, as revealed by hyperinsulinemic-euglycemic clamp studies.
Remarkably, the increased insulin sensitivity upon the activation of ARCGHR+
neurons was tissue-specific, as the insulin-stimulated glucose uptake was
specifically elevated in the skeletal muscle, in parallel with the increased
expression of muscle glycolytic genes. Overall, our results identify the
GHR-expressing neuronal population in the ARC as a major regulator of glycolysis
and muscle insulin sensitivity in vivo.




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