Impaired nicotinamide adenine dinucleotide (NAD+) metabolism in diabetes and diabetic tissues: Implications for nicotinamide ‐related compound treatment

Diabetes causes nicotinamide adenine dinucleotide metabolism dysregulation characterized by increasing consumption of nicotinamide adenine dinucleotide to produce nicotinamide and decreasing conversion of nicotinamide to nicotinamide adenine dinucleotide (salvage cascade) by biochemical abnormalities, which have been postulated for the etiology of diabetic complications. This results in increasing production of nicotinamide catabolites, which might cause oxidative stress. For diabetes patients, nicotinamide ‐related compounds, such as nicotinamide riboside and nicotinamide mononucleotide might be useful after correcting these abnormalities. AbstractOne of the biochemical abnormalities found in diabetic tissues is a decrease in the cytosolic oxidized to reduced forms of the nicotinamide adenine dinucleotide ratio (NAD+/NADH also known as pseudohypoxia) caused by oxidation of excessive substrates (glucose through the polyol pathway, free fatty acids and lactate). Subsequently, a decline in NAD+ levels as a result of the activation of poly adenine nucleotide diphosphate ‐ribose polymerase (mainly in type 1 diabetes) or the inhibition of adenine nucleotide monophosphate‐activated protein kinase (in type 2 diabetes). Thus, replenishment of NAD+ levels by nicotinamide ‐related compounds could be beneficial. However, these compounds also increase nicotinamide catabolites that cause oxidative stress. This is particularly troublesome for patients with diabetes, because they ...
Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: Review Article Source Type: research