pathway also activates oxidative stress.
Levels of Hexosamine
and Uronic acid were estimated by following the methods of Saeed et al, 2016 and Mojica et al, 2010 respectively (19, 20).
Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine
pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation.
 The glucose-induced pathologic features of DPN are well characterized and include enhanced activity of the polyol pathway, the formation of advanced glycation end products, PKC activation, enhanced modification of proteins with N-acetyl glucosamine through the hexosamine
pathway, increased inflammation, and a reduction in neurotrophic factors.
These include increased Protein C kinase activation, increased formation of advanced glycation end products (AGEs), accumulation of sorbitol via polyol pathway, reactive oxygen species (ROS) mediated cellular damage and increased flux through hexosamine
pathway.2 A recent addition to this list is down regulation of glyoxalase I (GLO I) in chronic hyperglycemia.3
As reported by Lemmers et al ., five types of N-glycans (FA2B, A2BG1, FA2G1, FA2BG1, and FA2BG1) that all contained ([sz]-1,4)-linked GlcNAc increased in the IgG of patients with type 2 diabetes compared to controls. In addition, previous studies showed that high levels of glucose can promote hexosamine
biosynthetic pathways and lead to the formation of excess GlcNAc and an increase of O-GlcNAc modifications. Degrell et al .
For example, glutamine is a known precursor amino acid for the synthesis of O-linked-Beta N-acetylglucosamine (Glc-NAc), one of the main initiators of the Hexosamine
Biosynthetic Pathway (HBP) [6-8].
Glycosaminoglycans are linear carbohydrate polymers that are composed of alternating uronate and hexosamine
saccharides linked by glyosidic linkages .
Rossetti et al., "Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine
pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation," Proceedings of the National Academy of Sciences of the United States of America, vol.
Various mechanisms contributing to the pathogenesis of DR such as inflammation, polyol pathway, accumulation of advanced glycation end products (AGEs), flux of hexosamine
pathway, and protein kinase C (PKC) activation are associated with the overproduction of ROS by the mitochondria .
The mechanisms involving DR development include the following: hyperglycaemia may cause sorbitol accumulation in retinal cells, increased polyol metabolism, advanced glycosylation end product (AGE) elevation in the extracellular fluid, increased protein kinase C and hexosamine
pathway activity , upregulation of growth factors and proinflammatory cytokines, hyperactivation of the renin-angiotensin system, and exacerbated production of superoxides.
The gastric mucus secretion, the content of gastric mucin and their precursor hexosamine
, is reduced.