Novel mutation in CYP21A2 gene causing the steroid 21-hydroxylase deficiency - C to G substitution in 7-position ofintron 2 acceptor splice site (c.290-7C>G) was identified. The effect of the mutation on splicing was checked in the system of CYP21A minigene expression in the cultured mammalian cells. The mutation impairs the usage of intron 2 acceptor splice site resulting in intron retention.

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The impairment of glucose homeostasis leads to hyperglycemia and type 2 diabetes mellitus. Glu cokinase (GK), an enzyme that catalyzes the conversion of glucose to glucose 6 phosphate in pancreatic β cells, liver hepatocytes, specific hypothalamic neurons, and intestine enterocytes, is a key regulator of glu cose homeostasis. In hepatocytes, GK controls the glucose uptake and glycogen synthesis and inhibits the glucose synthesis via the gluconeogenesis pathway. Glucokinase regulatory protein (GKRP) synthesized in hepatocytes acts as an endogenous GK inhibitor. During fasting, GKRP binds GK, inactivates it, and trans ports it into the cell nucleus, thus isolating it from the hepatocyte carbohydrate metabolism. In the beginning of the 2000s, the research was mainly focused on the development and trials of the small molecule GK acti vators as potential antidiabetic glucose lowering drugs. However, the use of such substances increased the risk of hypoglycemia, and clinical studies of most synthetic GK activators are currently discontinued. Allosteric inhibitors of the GK-GKRP interaction are coming as alternative agents increasing the GK activity that can substitute GKA. In this review, we discuss the recent advances and the current state of art in the development of potential antidiabetic drugs targeted to GK as a key regulator of glucose homeostasis.