Fig. 2.

The possible mechanisms for the effects of Propolis on hyperglycemia and hyperglycemia-induced renal damage. In diabetic patients, renal glucose uptake is increased in both the post-absorptive and postprandial states; however, muscle glucose uptake is either normal or reduced. Compensated increased glucose uptake in the kidney enhances ROS generation, eventually contributing to OS and pathogenetic pathways, which lead to renal tissue dysfunction. Propolis, by decreasing intestinal absorption of carbohydrate and expression of gluconeogenic genes in hepatocellular cells and elevating insulin production, cellular sensitivity to insulin, and the level of glycolysis in the liver, could alleviate hyperglycemia and prevent hyperglycemia-induced renal damage. Also, by its antioxidant properties, Propolis can reduce cellular dysfunction, inflammation, apoptosis, and fibrosis in kidney (Figure adapted from Fig. 2. in Ref. (6)). Abbreviations: ROS, reactive oxygen species; eNOS, endothelial nitric oxide synthase; PARP, poly ADP ribose polymerase; GAPDH, glyceraldehyde-3-dehydrogenase; AGE, advanced glycation end-product; DAG, diacylglycerol; DHAP, dihydroxyacetone phosphate; GFAT, glutamine fructose-6-phosphate amidotransferase; NF-κB, nuclear factor kappa B; PKC, protein kinase C; RAGE, receptor for AGE; UDP-GLcNAc, uridine diphosphate N-acetylglucosamine; PI3K, phosphatidylinositol 3-kinase; AMPK, 5'-adenosine monophosphate-activated protein kinase; GLUT 4, insulin-sensitive glucose transporter 4; IR, insulin receptor; Akt, serine/threonine protein kinase B; mTOR, mammalian target of rapamycin