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- Title
Identification of Hypothalamic Glucoregulatory Neurons That Sense and Respond to Changes in Glycemia.
- Authors
Deem, Jennifer D.; Tingley, David; Bjerregaard, Anne-Mette; Secher, Anna; Chan, Owen; Uzo, Chukwuemeka; Richardson, Nicole E.; Giering, Elizabeth; Doan, Tammy; Phan, Bao A.; Wu, Brandon; Scarlett, Jarrad M.; Morton, Gregory J.; Schwartz, Michael W.
- Abstract
To investigate whether glucoregulatory neurons in the hypothalamus can sense and respond to physiological variation in the blood glucose (BG) level, we combined continuous arterial glucose monitoring with continuous measures of the activity of a specific subset of neurons located in the hypothalamic ventromedial nucleus that express pituitary adenylate cyclase activating peptide (VMNPACAP neurons) obtained using fiber photometry. Data were collected in conscious, free-living mice during a 1-h baseline monitoring period and a subsequent 2-h intervention period during which the BG level was raised either by consuming a chow or a high-sucrose meal or by intraperitoneal glucose injection. Cross-correlation analysis revealed that, following a 60- to 90-s delay, interventions that raise the BG level reliably associate with reduced VMNPACAP neuron activity (P < 0.01). In addition, a strong positive correlation between BG and spontaneous VMNPACAP neuron activity was observed under basal conditions but with a much longer (~25 min) temporal offset, consistent with published evidence that VMNPACAP neuron activation raises the BG level. Together, these findings are suggestive of a closed-loop system whereby VMNPACAP neuron activation increases the BG level; detection of a rising BG level, in turn, feeds back to inhibit these neurons. To our knowledge, these findings constitute the first evidence of a role in glucose homeostasis for glucoregulatory neurocircuits that, like pancreatic β-cells, sense and respond to physiological variation in glycemia.
- Publication
Diabetes, 2023, Vol 72, Issue 9, p1207
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db23-0139