CRY1 dysregulation leads to hyperglycemia in diabetic mice

Abstract

Hepatic glucose production (HGP) is essential for maintenance of normal glucose homeostasis. Glucagon promotes hepatic gluconeogenesis to increase the level of blood glucose upon fasting. However, during the postprandial state, insulin suppresses HGP via FOXO1 regulation. In diabetes, HGP dysregulation and insulin resistance contributes to hyperglycemia. Recently, it has been reported that CRY1 could act as a potential suppressor of hepatic gluconeogenesis by FOXO1 protein degradation. We previously reported that the level of CRY1 protein was decreased in the liver of obese and diabetic animals. However, the underlying mechanism for hepatic CRY1 dysregulation has not been thoroughly elucidated. In order to find out which factors are involved in CRY1 degradation, we screened CRY1 binding proteins in the liver of diabetic mice. We discovered that several candidate proteins appear to physically associate with CRY1 to mediate its stability. Our data support that CRY1 binding proteins could regulate CRY1 protein stability, providing a clue to understand the mechanism for hyperglycemia through CRY1 dysregulation in the liver of diabetic mice.Support or Funding InformationThis work was supported by NRF of Korea Grant MSIP 2011‐0018312 and BK21.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.