Major Metabolic Hormone Responses to Exertional Heat Stroke in Mice

Disordered glucose metabolism has been shown to be a strong prognostic indicator of poor outcomes in heat stroke. In mice, within the first few hours of recovery from exertional heat stroke (EHS), glucose is reduced; however, by 24 h and for up to 4 days, sustained hyperglycemia has also been observed. To gain perspective on the underlying mechanisms that contribute to these responses we looked at circulating metabolic hormones responsible for glucose regulation. Male mice (n= 8, per group) ran in forced running wheels within an enclosed climatic chamber at 37.5°C/35% relative humidity (RH) until loss of cognitive function (approx. 2 h). Animals were sacrificed at 0.5h, 3h, 24h, 4d, 9d or 14d post‐EHS. Plasma samples were collected and metabolic hormones analyzed using Luminex multiplex technology or ELISA (corticosterone). Hormones secreted by the pancreas, amylin (p=0.02), c‐peptide (p=0.003), and insulin (p=0.003) were markedly suppressed at 0.5 h and continued to be suppressed at 3 h. Expected glucagon responses were absent during this period. Cytokines that influence glucose metabolism or uptake, IL‐6 and MCP‐1, displayed a significant increase at 0.5 and 3 h (p=0.0004, p=0.0008 respectively), with peak concentrations appearing at 0.5 h. Resistin (secreted by white adipose) was also significantly elevated at 0.5 h (p=0.003) and then decreased to low levels at 3h (p<0.002). Corticosterone was significantly elevated at the 0.5 h (p=0.0015) and 3 h time points (p=0.0009). These results may reflect, in part, hypoglycemia seen following exercise in the heat but are also consistent with transient organ dysfunction, specifically in the liver (i.e. failure to elevate glucose) and/or pancreas (suppression of insulin secretion without compensating glucagon response). Author views not official US Army or DoD policy. Supported by the Department of Defense W81XWH‐15‐2‐0038