KIU Publications

Type 2 diabetes mellitus was characterized by chronic hyperglycemia resulting from insulin resistance and impaired regulation of hepatic glucose production. Excessive hepatic gluconeogenesis was a major contributor to fasting hyperglycemia and remained incompletely controlled by conventional pharmacologic therapies. RNA interference therapeutics emerged as a promising molecular approach for selectively suppressing genes involved in hepatic glucose production. The purpose of this review was to evaluate the therapeutic potential of RNA interference strategies targeting hepatic gluconeogenic pathways in the management of Type 2 diabetes. A structured narrative review methodology was used to synthesize evidence from peer-reviewed studies examining molecular targets, delivery technologies, and metabolic outcomes of RNA interference interventions. Experimental findings demonstrated that small interfering RNA directed against key gluconeogenic regulators, including phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, forkhead box protein O1, and peroxisome proliferatoractivated receptor gamma coactivator 1 alpha, reduces hepatic glucose production and improves glycemic control in preclinical models. Liver-targeted delivery systems enhanced stability and facilitated efficient gene silencing within hepatocytes. These approaches provided sustained metabolic improvements with reduced systemic toxicity compared with conventional pharmacotherapy. RNA interference therapeutics represented a promising strategy for selective regulation of hepatic metabolism in Type 2 diabetes. Continued clinical investigation and optimization of delivery systems were recommended to support translation into routine metabolic disease management.