Figure 3.
Graphs depicting the ability to sense glycopenia, a state of systemic glucose shortage, in mice lacking both pancreatic and neuronal, only neuronal, or only pancreatic KATP channels labeled from A to C show that without functional pancreatic KATP channels, mice have amplified response to glycopenia and release more glucose into systemic circulation. Graphs indicating the secreted glucagon and insulin levels upon glycopenia induction in mice lacking both pancreatic and neuronal and only pancreatic functional KATP channels labeled from D to E demonstrate that the lack of functional pancreatic KATP channels does not attenuate glycopenia-induced counter-regulatory responses, in which all mice showed increased levels of glucagon, but impairs glucose-stimulated insulin secretion that is expected to be activated after the glycopenia-induced glucose increase.

Glycopenia-induced counter-regulatory mechanisms are regulated by pancreatic but not neuronal KATP channels. (A-C) Blood glucose levels during 2DG-induced glycopenia assessment in WT vs Kir6.2 KO (A), NestinCre/0; Kir6.2flox/+ vs flox/flox (B), and Ins1Cre/0; Kir6.2flox/+ vs flox/flox mice (C). (D-E) Plasma glucagon (D) and insulin concentration (E) after a 6-hour fasting duration (Before 2DG injection) and 30 minutes after 2DG injection (After 2DG injection) in WT, Kir6.2 KO, Ins1Cre/0; Kir6.2flox/+, and Ins1Cre/0; Kir6.2flox/flox mice. WT: n = 8 (A), 10 (D, E); Kir6.2 KO: n = 8 (A), 9 (D), 10 (E); Ins1Cre/0; Kir6.2flox/+: 5 (C, E), 4 (D); Ins1Cre/0; Kir6.2flox/flox: n = 10 (C), 5 (D), 6 (E); NestinCre/0; Kir6.2flox/+: n = 10 (B); NestinCre/0; Kir6.2flox/flox: n = 8 (B). Statistical comparisons were made by two-way ANOVA with Šídák’s correction (A-C) and two-way ANOVA with Tukey’s correction followed by multiple comparisons (D-E). Data are represented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns: not significant.

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