The GABBR1/miR-19b-3p/WNT2B axis regulates insulin resistance and liver injury in diabetes with viral infection: mechanistic and therapeutic insights

Insulin resistance (IR) is the main feature of type 2 diabetes mellitus. Furthermore, viral infection can aggravate the abnormal glucose metabolism in diabetic patients. GABBR1 can maintain normal glucose homeostasis, but its specific role in diabetes is not clear. We investigated the function of the GABBR1/miR-19b-3p/WNT2B axis <i>in vitro</i> and <i>in vivo</i>. miR-19b-3p and GABBR1 were overexpressed or knocked down in AML12 cells. Subsequently, these cells were treated with palmitic acid (PA) to induce damage or poly I : C to mimic viral infection. The degree of AML12 cell damage was assessed using the CCK-8 assay; inflammation levels were measured using ELISA; and IR indexes were determined using the Immunofluorescence kit and Western blot assay. The diabetic mice model was established to evaluate liver injury and IR. PA and poly I : C can reduce the activity of AML12 cells, increase apoptosis and inflammatory factor contents, weaken the ability of glucose uptake and consumption, enhance the production capacity, and reduce the level of GLUT4. GABBR1 mediates the targeted regulation of WNT2B by miR-19b-3p. PA and poly I : C also increased ALT, AST, inflammatory factors and miR-19b-3p levels, and decreased GABBR1 and WNT2B expression of mice. Liver cells showed swelling and many spherical lipid droplets. After miR-19b-3p knockdown and GABBR1 overexpression, the degree of liver injury and IR in AML12 cells and mice were alleviated. GABBR1 regulates miR-19b-3p/WNT2B axis to reduce liver injury, IR and inflammatory response, and improve the comorbidity of diabetes and viral infection. This pathway represents a potential therapeutic target for mitigating the comorbidity of diabetes and viral infection.