Methylglyoxal: a new therapeutic target for obesity and diabetes

Abstract

Methylglyoxal (MG), a highly reactive dicarbonyl compound, is mainly derived from glucose and fructose metabolism, and can also be derived from food, which is an important ingredient in food additives. MG can make protein and DNA react to form advanced glycosylated end products (AGEs), which is cytotoxic. By directly inducing oxidative stress, MG increases intracellular reactive oxygen species, leading to cell metabolic disorders and apoptosis. In patients with metabolic abnormalities and diabetes, the accumulation of this abnormal dicarbonyl metabolite causes an increase in DNA and protein remodeling, leading to dysfunction of cell and tissue functions, aging and disease. In obese patients with impaired metabolism and diabetic patients, MG level is significantly increased, which is an important risk signal for metabolic disorders and vascular complications. The systematic metabolism of glyoxalase can detoxify MG and make it into non-toxic lactate salt to be expelled from the body, which is not enough to produce toxic reaction. Increasing the activity of glyoxalase 1 can degrade MG and inhibit the production of AGEs to achieve detoxification. Through the way of detoxifying MG, it provides a new idea for the diagnosis and treatment for diabetes. Key words: Methylglyoxal; Dicarbonyl stress; Obesity; Diabetes mellitus