Podocyte resistance to the actions of insulin on glucose transport could contribute to the pathogenesis of diabetic podocytopathy (DP) via disturbances in cyclic-dependent protein kinase signaling. To determine whether cGMP-dependent protein kinase (PKG) is involved in the insulin regulation of glucose transport, we measured insulin-dependent glucose uptake into cultured rat podocytes under conditions of modified PKG activity using pharmacological (PKG activator or inhibitor) and biochemical (siRNA PKGI alpha, siRNA insulin receptor beta) means. Our findings indicate the participation of PKG in insulin-stimulated transport and provide new insights into how PKG may trigger the resistance of glucose transport to insulin in DP. (c) 2014 Elsevier Inc. All rights reserved.