Gck-KO Mouse

Gck, or glucokinase, is a key regulatory enzyme in pancreatic beta-cells. It acts as a glucose sensor, playing a crucial role in insulin secretion regulation. It is also involved in glycogen synthesis in the liver and is central to glucose metabolism and maintaining glucose homeostasis [3,4].

Heterozygous inactivating mutations of the Gck gene cause GCK-MODY, a common form of Maturity Onset Diabetes of the Young (MODY), characterized by fasting hyperglycemia without worsening with aging and low risk of chronic vascular complications [1]. Homozygous inactivating GCK mutations result in permanent neonatal diabetes mellitus (PNDM) [3,6]. Additionally, heterozygous activating GCK mutations can cause hypoglycemia [3,6]. The penetrance of pathogenic GCK variants is high across different cohorts (89%-97%), and most people with GCK-MODY do not need pharmacotherapy, except pregnant women with non-GCK-mutated fetuses [1,2]. Dorzagliatin, a glucokinase activator, was effective and safe in a GCK-MODY patient [5].

In conclusion, Gck is essential for glucose metabolism, insulin secretion, and glycogen synthesis. Genetic studies on Gck-related mutations have revealed its significant role in various forms of diabetes, including GCK-MODY and PNDM, and understanding its functions can provide insights into the pathogenesis and treatment of these diseases [1,3,4,5].