0047 Light at Night Worsens Metabolic Dysfunction in a Polygenic Mouse Model of Type 2 Diabetes Mellitus

Abstract Introduction Electric lighting at night has many benefits for modern society; however, several studies have reported deleterious effects on health. Exposure of nondiabetic mice to dim levels of light at night (LAN) impairs glucose tolerance, whereas a return to dark nights (LD) reverses this impairment. TALLYHO/JngJ (TH) mice are a polygenic mouse model of type 2 diabetes mellitus (T2DM). We predicted that exposure to LAN will worsen the metabolic abnormalities in TH mice, and these effects will be reversed when mice are returned to LD. Methods Male TH mice were exposed to LD (n=29) or LAN (40 lux, n=29) in 2 separate cohorts. After 8 weeks, intraperitoneal glucose tolerance testing (ipGTT) was performed followed by intraperitoneal insulin tolerance testing (ipITT) on a separate day. In cohort 1, all mice were then returned to dark nights for 4 weeks, and the ipITT was repeated. In cohort 2, tissues were collected for analysis after recovery from the ipITT. Results TH mice housed in LAN had increased body weight, impaired glucose tolerance, and higher insulin resistance than mice housed in LD. Insulin resistance was improved when mice were returned to LD for 4 weeks. More mice developed T2DM (LD = 48.28%, LAN = 79.31%, Fisher’s exact test, p=0.03), and survival rate decreased when mice were housed in LAN. At the end of the 8-wk exposure, the percent survival in LD was 77.8% and 33.3% in LAN. Conclusion LAN worsens the metabolic abnormalities in a polygenic rodent model of T2DM and these effects were reversed upon return to dark nights. The decreased survival in the TH mice exposed to LAN is a surprise finding that requires further investigation. Limiting LAN may be a simple intervention that could benefit humans with T2DM, but would require further studies. Support (If Any) This study was supported by the Schulte Research Foundation, National Institutes of Health R21CA202745 and R01NS092388.