Abstract
Glucose homeostasis is maintained through interplay between central and peripheral control mechanisms which are aimed at storing excess glucose following meals and mobilizing these same stores during periods of fasting. The nucleus of the solitary tract (NST) in the dorsal medulla has long been associated with the central detection of glucose availability and the control of glucose homeostasis. Recent evidence has emerged which supports the involvement of astrocytes in glucose homeostasis. The aim of the present study was to investigate whether NST-astrocytes respond to physiologically relevant decreases in glucose availability, in vitro, as well as to the presence of the glucoprivic compound 2-deoxy-D-Glucose. This report demonstrates that some NST-astrocytes are capable of responding to low glucose or glucoprivation by increasing cytoplasmic calcium; a change that reverses with restoration of normal glucose availability. While some NST-neurons also demonstrate an increase in calcium signaling during low glucose availability, this effect is smaller and somewhat delayed compared to those observed in adjacent astrocytes. TTX did not abolish these hypoglycemia mediated responses of astrocytes, suggesting that NST-astrocytes may be directly sensing low glucose levels as opposed to responding to neuronal detection of hypoglycemia. Thus, chemodetection of low glucose by NST-astrocytes may play an important role in the autonomic regulation of glucose homeostasis.
Highlights
Glucose is the primary energy source for cellular metabolism
The relative changes in cytoplasmic calcium were expressed as percent changes in fluorescence [( F/F)%] of the Calcium Green AM (CAG) reporter dye, where F is the intensity of the baseline fluorescence signal before stimulation, and F is the difference between the peak fluorescence intensity and the baseline signal (Figures 2, 4, 5)
The dorsal medulla and nucleus of the solitary tract (NST) have long been associated with the central detection of the glucose availability and the control of the glycemic state (Bernard, 1855; Marty et al, 2007; Grill and Hayes, 2012)
Summary
Glucose is the primary energy source for cellular metabolism. the maintenance of appropriate serum glucose levels is critical for organismal survival. NST receives descending inputs from hypothalamic nuclei such as the lateral and paraventricular nuclei that are associated with glucose homeostasis (Marty et al, 2007; Geerling et al, 2010; Biag et al, 2012). Due to this confluence of signals regarding glucose availability as well as its inputs to pre-autonomic nuclei, the NST plays a predominate role in central control of glucose homeostasis (Adachi et al, 1995; Grill and Hayes, 2012)
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