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. Author manuscript; available in PMC: 2022 Mar 2.
Published in final edited form as: Cell Metab. 2021 Jan 14;33(3):676–687.e5. doi: 10.1016/j.cmet.2020.12.018

Figure 3. AgRP neurons detect SGLT-1-mediated glucose uptake into the intestinal epithelium.

Figure 3.

(A) Glucose is transported into the intestinal epithelial cells by Sodium-Glucose Linked Transporter 1 (SGLT1) and out of the cells by glucose transporter 2 (GLUT2). (B) Average ΔF/F of GCaMP6s signals in AgRP neurons of food-restricted mice during intra-duodenal (ID) infusions of 8% glucose (top), 8% glucose with the SGLT1/3 inhibitor phlorizin (0.4%, middle) and 8% glucose with the GLUT2 inhibitor phloretin (0.23%, bottom). Signals are aligned to the start of the infusion. Green, 470-nm control signal; grey, 405-nm control signal. Dark lines represent means and lighter shaded areas represent SEM. (C) Mean ΔF/F of the 470-nm signal (1-min bins) in AgRP neurons during ID infusions of glucose solutions in (B) (n=4-7/group, two-way repeated measures ANOVA, p<0.001). (D) Minimum ΔF/F of the 470-nm signal during ID infusions of glucose solutions in (B) (n=4-7/group, one-way ANOVA, p<0.01). (E) Mean ΔF/F of the 470-nm signal from 0 to 10 minutes during ID infusions of glucose solutions in (B) (n=4-7/group, one-way ANOVA, p<0.01). (F) Mean ΔF/F of the 470-nm signal (3-min bins) in AgRP neurons with ID infusions of water; 8% glucose, mannitol, methyl α-D-glucopyranoside (MDG), 3-o-methylglucose (3-oMG), or glucose, or equi-osmotic (1.8%) NaCl (n=5-7/group, two-way repeated measures ANOVA, p<0.001). Signals were aligned to the start of the infusion. (G) Mean ΔF/F of the 470-nm signal (3-min bins) in AgRP neurons with ID infusions of 16% mannitol, MDG, 3-oMG, or glucose, or NaCl (2.7%) or urea (5.6%) (n=4-7/group, two-way repeated measures ANOVA, p<0.001). (H) Mean ΔF/F of the 470-nm signal from 0 to 30 min following duodenal infusion of glucose and SGLT agonists. Low concentrations from (F) are in light blue and high concentrations from (G) are in dark blue (n=4-7/group, one-way repeated ANOVA, p<0.01). (I) Mean ΔF/F of the 470-nm signal from 0 to 30 min following duodenal infusion of non-nutritive NaCl, mannitol, and urea. Low concentrations from (F) are in light blue and high concentrations from (G) are in dark blue (n=4-6/group, one-way repeated ANOVA, p<0.01). Data are expressed as mean ± SEM, ns p>0.05, t-tests and post-hoc comparisons: *p<0.05, **p<0.01, ANOVA interaction: ∞∞∞p<0.001; ANOVA main effect of group: ☼p<0.05, ☼☼p<0.01, ☼☼☼p<0.001.

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