Analysis Tools
homeostasis/metabolism
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• 8-week-old male mutants do not show differences in body weight, daily food intake, ad libitum-fed blood glucose levels, or overnight fasted blood glucose levels
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• 8-week-old males display impaired glucose tolerance (elevated blood glucose after injection of glucose at 2 g/kg body weight) compared to control littermates
• no alterations in pancreatic beta cells is observed due to ectopic cre expression resulting in mutant Kcnj11 expression in beta cells
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nervous system
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• only about 14% of Pmch neurons show spontaneous action potentials at 5 mM glucose in brain slice preparations compared to 30% of neurons in wild-type preparations, indicating disrupted glucose-sensing
• membrane resistance of Pmch neurons is significantly reduced relative to wild-type neurons at 5 mM glucose
• almost all neurons do not hyperpolarize when extracellular glucose is reduced from 5 to 1 mM whereas around 70% of control neurons hyperpolarize under these conditions, indicating disrupted glucose-sensing
• glucose-induced depolarization is abrogated in Pmch neurons, but is readily observed in control Pmch neurons, indicating disrupted glucose-sensing
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