Identification of Hypothalamic Glucoregulatory Neurons That Sense and Respond to Changes in Glycemia

• DOI: 10.2337/db23-0139
• Publication Date: 2023-06-23T01:03:23Z
• Authors: Jennifer D. Deem; David Tingley; Anne-Mette Bjerre...; Anna Secher; Owen Chan; Chukwuemeka Uzo; Nicole E. Richardson; Elizabeth Giering; Tammy Doan; Bao A. Phan; Brandon Wu; Jarrad M. Scarlett; Gregory J. Morton; Michael W. Schwartz
• Keywords: Basal (medicine)

To investigate whether glucoregulatory neurons in the hypothalamus can sense and respond to physiological variation blood glucose (BG) level, we combined continuous arterial monitoring with measures of activity a specific subset located hypothalamic ventromedial nucleus that express pituitary adenylate cyclase activating peptide (VMNPACAP neurons) obtained using fiber photometry. Data were collected conscious, free-living mice during 1-h baseline period subsequent 2-h intervention which BG level was raised either by consuming chow or high-sucrose meal intraperitoneal injection. Cross-correlation analysis revealed that, following 60- 90-s delay, interventions raise reliably associate reduced VMNPACAP neuron (P < 0.01). In addition, strong positive correlation between spontaneous observed under basal conditions but much longer (∼25 min) temporal offset, consistent published evidence activation raises level. Together, these findings are suggestive closed-loop system whereby increases level; detection rising turn, feeds back inhibit neurons. our knowledge, constitute first role homeostasis for neurocircuits like pancreatic β-cells, glycemia. Article Highlights By combining photometry, studies investigated murine detect changes glycemia vivo. rapidly decreases (within <2 when is food consumption administration. Spontaneous also correlates positively glycemia, reports hyperglycemia induced experimental Like appear