Hypothalamic astroglial connexins are required for brain glucose sensing-induced insulin secretion.
J Cereb Blood Flow Metab. 2013-12-04; 34(2): 339-346
DOI: 10.1038/jcbfm.2013.206
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Hypothalamic glucose detection participates in maintaining glycemic balance, food
intake, and thermogenesis. Although hypothalamic neurons are the executive cells
involved in these responses, there is increasing evidence that astrocytes
participate in glucose sensing (GS); however, it is unknown whether astroglial
networking is required for glucose sensitivity. Astroglial connexins 30 and 43
(Cx30 and Cx43) form hexameric channels, which are apposed in gap junctions,
allowing for the intercellular transfer of small molecules such as glucose
throughout the astroglial networks. Here, we hypothesized that hypothalamic
glucose sensitivity requires these connexins. First, we showed that both Cxs are
enriched in the rat hypothalamus, with highly concentrated Cx43 expression around
blood vessels of the mediobasal hypothalamus (MBH). Both fasting and high
glycemic levels rapidly altered the protein levels of MBH astroglial connexins,
suggesting cross talk within the MBH between glycemic status and the connexins’
ability to dispatch glucose. Finally, the inhibition of MBH Cx43 (by transient
RNA interference) attenuated hypothalamic glucose sensitivity in rats, which was
demonstrated by a pronounced decreased insulin secretion in response to a brain
glucose challenge. These results illustrate that astroglial connexins contribute
to hypothalamic GS.