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. Author manuscript; available in PMC: 2018 Aug 22.
Published in final edited form as: Nat Med. 2015 Apr 6;21(5):506–511. doi: 10.1038/nm.3787

Figure 4. Intraduodenal infusion of metformin lowers GP in obese and diabetic rats, while the overall acute glucose-lowering effect of a bolus intragstric treatment of metformin is dependent on duodenal AMPK signaling.

Figure 4

(a) Experimental procedure and pancreatic (basal-insulin) euglycemic clamp protocol for 28 day HFD-fed rats. (b,c) The glucose infusion rate (b), rate of GP (c) during the pancreatic (basal insulin) euglycemic clamp in 28 day HFD-fed rats with intraduodenal saline or metformin infusion (***p < 0.001, versus saline as compared by unpaired t-test; n=6 for each group). (d,e) Plasma glucose levels (d) and the rate of GP (e) in NA-STZ/HFD induced hyperglycemic rats with intraduodenal saline or metformin (n=8 for each group). (f) Experimental procedure and gastric infusion protocol. (g,h) The plasma glucose levels (different letter denotes significant difference of p < 0.05 between groups as calculated by two-way ANOVA with Tukey’s post hoc test) (g) and the percent suppression of plasma glucose from basal levels (**p < 0.01, versus saline as compared by unpaired t-test within each timepoint) (h) in NA-STZ/HFD induced hyperglycemic rats injected with either intraduodenal GFP or dnAMPK for 5 days with a gastric bolus treatment of metformin (n=8 for each group). Values are shown as mean ± s.e.m. Unless noted, ***p < 0.001, versus saline, as calculated by one-way ANOVA with Tukey’s post hoc test. GP, glucose production; AMPK, AMP-activated protein kinase; NA, nicotinamide; STZ, streptozotocin. HFD, high fat diet.