Methylglyoxal, A Metabolite Increased in Diabetes is Associated with Insulin Resistance, Vascular Dysfunction and Neuropathies

Abstract

Diabetes mellitus is a pandemic metabolic disease characterized by chronically elevated blood glucose concentration due to insulin dysfunction. Diabetics are prone to limbs fungal infections and ulcers due to vascular injury and end-organ damage such as nephropathy, retinopathy and neuropathic pain all of which are associated with methylglyoxal elevation. Methylglyoxal is generated through carbohydrate, lipid and protein metabolism which are all found to be exacerbated in diabetes. Moreover, methylglyoxal is highly reactive with various cellular and interstitial molecules such as proteins and phospholipids to form stable adducts and advanced glycation end products. Methylglyoxal induces insulin resistance, pancreatic β-cells cytotoxicity, and induces endothelial dysfunction that accelerates retinopathy, another diabetes complication. Additionally, methylglyoxal induces hyperalgesia and neuronal inflammation associated with neuropathic pain. Therefore, methylglyoxal might represent a potential therapeutic target in diabetes and associated complications.2

Diabetic dyslipidaemia is associated with alterations in eNOS, caveolin‐1, and endothelial dysfunction in streptozotocin treated rats

“…Significance is represented as *P ˂ .05 versus control when analysed through 2 tailed unpaired student t test furthermore, given carbohydrates can no longer be utilized efficiently as an energy source, this leads to a greater reliance on energy from fat and protein to meet the energy demands of the animal. 19 Similar to previous findings in type 2 diabetic patients, we observed a relationship between serum Ox-LDL concentrations and serum TG concentrations in our STZ-diabetic rats. 18 In patients with type-2 diabetes, hyperglycaemia enhances the oxidative stress, further modifying LDL into Ox-LDL, which is likely occurring in our type 1 hyperglycaemic STZ diabetic rats.…”

“…In adipose tissues, insulin suppresses lipolysis by inhibiting the activity of hormone sensitive lipase, which catalyses the mobilization of free fatty acids from stored TGs . The STZ‐mediated destruction of the pancreatic β‐cells results in an insulinopaenic state in STZ‐diabetic rats, and hence, the lack of insulin will result in an increased lipolysis of TG‐rich lipoproteins (LDL and TGs), and furthermore, given carbohydrates can no longer be utilized efficiently as an energy source, this leads to a greater reliance on energy from fat and protein to meet the energy demands of the animal …”

Glycation in Huntington’s Disease: A Possible Modifier and Target for Intervention

“…Increased sugar levels lead to a number of metabolic changes including oxidative stress, antioxidant depletion, neuro-inflammation, electrophysiological deficits and hormonal responses [56]. Importantly, the levels of methylglyoxal (MGO), a potent glycating agent, are elevated in diabetic patients, most likely due to hyperglycemia [57]. Consistently, higher AGE levels were detected in diabetic patients and in animal models of diabetes [58,59].…”

Use of low-carbohydrate diets in patients with type 2 diabetes

“…Despite the improved lipid profile parameters, other markers of atherosclerosis may deteriorate due to its use. High methylglyoxal levels forming under ketogenic conditions are considered a risk factor for vascular and other tissue damage, and are largely responsible for diabetic complications and the impairment of insulin action [15,16]. Low/very low intakes of carbohydrate food sources may impact the overall diet quality and the long-term effects of such drastic diet changes remain at present unknown.…”