Attenuation of hyperglycemia and amadori products by aminoguanidine in alloxan-diabetic rabbits occurs via enhancement in antioxidant defenses and control of stress.

The micro- and macro-complications in diabetes mellitus (DM) mainly arise from the damage induced by Amadori and advanced glycation end products, as well as the released free radicals. The primary goal of DM treatment is to reduce the risk of micro- and macro-complications. In this study, we looked at the efficacy of aminoguanidine (AG) to prevent the production of early glycation products in alloxan-diabetic rabbits. Type1 DM was induced in rabbits by a single intravenous injection of alloxan (90 mg/kg body weight). Another group of rabbits was pre-treated with AG (100 mg/kg body weight) prior to alloxan injection; this was followed by weekly treatment with 100 mg/kg of AG for eight weeks. Glucose, insulin, and early glycation products (HbA1C and fructosamine) were measured in control, diabetic and AG treated diabetic rabbits. The effects of hyperglycemia on superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), reduced glutathione (rGSH), nitric oxide, lipid peroxides, and protein carbonyl were investigated. Alloxan-diabetic rabbits had lower levels of SOD, CAT, Gpx, and rGSH than control rabbits. Nitric oxide levels were considerably greater. AG administration restored the activities of SOD, CAT, Gpx enzymes up to 70-80% and ameliorated the nitric oxide production. HbA1c and fructosamine levels were considerably lower in AG-treated diabetic rabbits. The observed control of hyperglycemia and amadori adducts in alloxan-diabetic rabbits by AG may be attributed to decrease of stress and restoration of antioxidant defenses.

The receptor for advanced glycation end products: A fuel to pancreatic cancer.

The receptor for advanced glycation end products (RAGEs) was first illustrated in the year 1992. RAGE is a single-transmembrane and multi-ligand component of the immunoglobulin protein super family. The engagement of RAGE turns out to an establishment of numerous intracellular signalling mechanisms resulting in the progression and perpetuation of many types of cancer including, the pancreatic cancer. The present review primarily focuses on the multi-ligand activation of RAGEs leading to the downstream signalling cascade activation. The kick start of the RAGEs activation leads to the several anomalies and includes multiple types of cancers. The RAGE expression correlates well with the survival of pancreatic cancer cells leading to the myeloid response. RAGEs assist in the tumourogenesis which enhance and thrive to its fullest in the stressed tumour microenvironment. An improved perceptive of its involvement in pancreatic cancer may offer novel targets for tumour supervision and risk measurement.