Fig. 1: HPA axis mediated hyperglycemia.

a Experimental paradigm for chemogenetic activation of PVN^CRH neurons in Crh-Cre mice (top). The firing rate of PVN^CRH neurons increased after treatment with 10 μM CNO (down). b Activation of PVN^CRH neurons significantly increased glucose levels (n = 7 per group). *p = 0.039. c Experimental paradigm for optogenetic stimulation of PVN^CRH in Crh-Cre mice (top). Example trace showing the firing rate of PVN^CRH neurons in response to blue light exposure (down). d Photo-stimulation of CRH neurons increased glucose levels compared to control (injected with AAV-DIO-GFP, n = 7 per group). *p = 0.022. e Experimental paradigm for optogenetic inhibition of PVN^CRH in Crh-Cre mice during footshock stress. f Example trace showing the firing rate of CRH neurons in response to yellow light exposure. g Inhibition of PVN^CRH neurons significantly suppressed stress-induced blood glucose (p = 0.015, n = 7 for control and n = 6 for eNpHR). Post-hoc test: control vs eNpHR, **p = 0.003 (fast), *p = 0.022 (delay); for control: $$$p < 0.001, compared to baseline. h Experimental paradigm for footshock stress in intact and adrenalectomized (ADX) mice. i Footshock stress increased blood glucose levels in both fast (p = 0.004) and delay stages (p = 0.016) (n = 6 per group). Post-hoc test showed increased fast glucose levels in both sham (**p = 0.001) and ADX (&p = 0.014) group when compared to control group (without stress). While sham group showed higher delay glucose than control (**p = 0.005) and ADX (#p = 0.048) group. When compared to baseline, $$p = 0.008 for sham and ^p = 0.018 for ADX group. j Experimental paradigm for footshock stress with/out CORT108297 injection. k Footshock stress increased glucose levels in both fast (p = 0.02) and delay stages (p = 0.003) (n = 6 for control, n = 7 for other two groups). Post-hoc test: footshock vs control, *p = 0.014 (fast), **p = 0.001 (delay); CORT108297+footshock vs control, &p = 0.014 (fast); footshock vs CORT108297+footshock, #p = 0.016 (delay). When compared to baseline, $$p = 0.002 (Footshock) and ^^^p < 0.001 (CORT108297+footshock). Multi-time point data were analyzed by two-way repeated-measures ANOVA with LSD post hoc comparison, otherwise use two-sided t test. All data shown as means ± SEM. Source data are provided as a Source Date file.