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ARCGHR Neurons Regulate Muscle Glucose Uptake

Authors :
Juliana Bezerra Medeiros de Lima
Lucas Kniess Debarba
Alan C. Rupp
Nathan Qi
Chidera Ubah
Manal Khan
Olesya Didyuk
Iven Ayyar
Madelynn Koch
Darleen A. Sandoval
Marianna Sadagurski
Source :
Cells, Vol 10, Iss 5, p 1093 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

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.

Details

Language :
English
ISSN :
20734409
Volume :
10
Issue :
5
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.236b9e73daf24ccba68ad883f0c0a5cc
Document Type :
article
Full Text :
https://doi.org/10.3390/cells10051093