Fig. 2. Chronic CNO treatment of SKM-Gs-DREADD mice improves glucose tolerance by enhancing glucose uptake into SKM.

Prior to metabolic testing, control and SKM-GsD mice consumed drinking water containing CNO (250 mg/l; CNO H₂O) for 7 days. All studies were carried out with male mice that were at least 8 weeks old. a Glucose tolerance test (GTT), lean control (n = 6), and SKM-GsD mice (n = 5, overnight fasted) injected i.p. with glucose (2 g/kg). *p < 0.05, Student’s t-test, #p < 0.05, repeated-measure two-way ANOVA, genotype effect. b Insulin tolerance test (ITT), lean control (n = 6) and SKM-GsD mice (n = 5, fasted for 4 h) injected i.p. with insulin (0.75 IU/kg). c Glucose-stimulated insulin secretion (GSIS), lean control (n = 6), and SKM-GsD mice (n = 5, overnight fasted) injected i.p. with glucose (2 g/kg). d GTT, HFD-induced obese control, and SKM-GsD mice (overnight fasted) injected i.p. with glucose (1 g/kg) (n = 7/group). *p < 0.05, Student’s t-test, #p < 0.05, repeated-measure two-way ANOVA, genotype effect. e ITT, HFD-induced obese control, and SKM-GsD mice (fasted for 4 h) injected i.p. with insulin (1.5 IU/kg) (n = 6/group). f GSIS, HFD-induced obese control (n = 7), and SKM-GsD mice (n = 6, overnight fasted) injected i.p. with glucose (1 g/kg). g In vivo 2-deoxyglucose (2-DG) uptake studies. Lean control (n = 7) and SKM-GsD mice (n = 6, overnight fasted) that were maintained on CNO drinking water for 7 days were injected with glucose (2 g/kg i.p.) containing 10 μCi of [¹⁴C]2-DG. Two hours after injections, tissues were collected and the [¹⁴C]2-DG-6-phosphate content was determined in the indicated tissues. Quad, quadriceps muscle; Gastrocn, gastrocnemius muscle; WAT, white adipose tissue; BAT, brown adipose tissue. Data are presented as means ± SEM. *p < 0.05 (unpaired two-tailed Student’s t-test). Source data are provided as a Source data file.