Type 2 diabetic mice enter a state of spontaneous hibernation-like suspended animation following accumulation of uric acid.

ABSTRACT: Hibernation is an example of extreme hypometabolic behavior. How mammals achieve such a state of suspended animation remains unclear. Here we show that several strains of type 2 diabetic mice spontaneously enter into hibernation-like suspended animation (HLSA) in cold temperatures. Nondiabetic mice injected with ATP mimic the severe hypothermia analogous to that observed in diabetic mice. We identified that uric acid, an ATP metabolite, is a key molecular in the entry of HLSA. Uric acid binds to the Na⁺ binding pocket of the Na⁺/H⁺ exchanger protein and inhibits its activity, acidifying the cytoplasm and triggering a drop in metabolic rate. The suppression of uric acid biosynthesis blocks the occurrence of HLSA, and hyperuricemic mice induced by treatment w

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC8484811 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature