Format

Send to

Choose Destination
Mol Cell Endocrinol. 2014 Jan 25;382(1):262-270. doi: 10.1016/j.mce.2013.10.013. Epub 2013 Oct 18.

Glucose sensing mechanisms in hypothalamic cell models: glucose inhibition of AgRP synthesis and secretion.

Author information

1
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
2
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON M5S 1A8, Canada; Division of Cellular and Molecular Biology, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5S 1A8, Canada. Electronic address: d.belsham@utoronto.ca.

Abstract

Glucose-sensing neurons play a role in energy homeostasis, yet how orexigenic neurons sense glucose remains unclear. As models of glucose-inhibited (GI) neurons, mHypoE-29/1 and mHypoA-NPY/GFP cells express the essential orexigenic neuropeptide AgRP and glucose sensing machinery. Exposure to increasing concentrations of glucose or the glucose analog 2-deoxyglucose (2-DG) results in a decrease in AgRP mRNA levels. Taste receptor, Tas1R2 mRNA expression was reduced by glucose, whereas 2-DG reduced Tas1R3 mRNA levels. Increasing glucose concentrations elicited a rise in Akt and neuronal nitric oxide synthase (nNOS) phosphorylation, CaMKKβ levels, and a reduction of AMP-kinase alpha phosphorylation. Inhibitors of NOS and the cystic fibrosis transmembrane conductance regulator (CFTR) prevented a decrease in AgRP secretion with glucose, suggesting a pivotal role for nNOS and the CFTR in glucose-sensing. These models possess the hallmark characteristics of GI neurons, and can be used to disentangle the mechanisms by which orexigenic neurons sense glucose.

KEYWORDS:

AMPK; Agouti-related peptide; Glucose; Hypothalamus; Neuropeptide

PMID:
24145125
DOI:
10.1016/j.mce.2013.10.013
[Indexed for MEDLINE]

Publication type, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center