Nutraceutical Prevention of Diabetic Complications—Focus on Dicarbonyl and Oxidative Stress

Abstract

Oxidative and dicarbonyl stress, driven by excess accumulation of glycolytic intermediates in cells that are highly permeable to glucose in the absence of effective insulin activity, appear to be the chief mediators of the complications of diabetes. The most pathogenically significant dicarbonyl stress reflects spontaneous dephosphorylation of glycolytic triose phosphates, giving rise to highly reactive methylglyoxal. This compound can be converted to harmless lactate by the sequential activity of glyoxalase I and II, employing glutathione as a catalyst. The transcription of glyoxalase I, rate-limiting for this process, is promoted by Nrf2, which can be activated by nutraceutical phase 2 inducers such as lipoic acid and sulforaphane. In cells exposed to hyperglycemia, glycine somehow up-regulates Nrf2 activity. Zinc can likewise promote glyoxalase I transcription, via activation of the metal-responsive transcription factor (MTF) that binds to the glyoxalase promoter. Induction of glyoxalase I and metallothionein may explain the protective impact of zinc in rodent models of diabetic complications. With respect to the contribution of oxidative stress to diabetic complications, promoters of mitophagy and mitochondrial biogenesis, UCP2 inducers, inhibitors of NAPDH oxidase, recouplers of eNOS, glutathione precursors, membrane oxidant scavengers, Nrf2 activators, and correction of diabetic thiamine deficiency should help to quell this.

Untitled

“…Oxidative stress can cause biochemical alterations in glucose and lipid metabolism as frequently observed in the patients of diabetes mellitus. Zinc supplementation helps to improve anti-oxidant status and decreases the chances of lipid peroxidation, but the studies showing beneficial effects of zinc supplementation were not exclusive for zinc only because other anti-oxidant vitamins and minerals were co-administered in these studies 31 .…”

Anti-Glycation Properties of Zinc-Enriched Arthrospira platensis (Spirulina) Contribute to Prevention of Metaflammation in a Diet-Induced Obese Mouse Model

“…Similarly, synergist effects between components of spirulina phytocomplex and zinc could contribute to the antioxidant effects here recorded. Indeed, in addition to its action as a cofactor of Cu/Zn-SOD and other antioxidant enzymes [ 47 ], zinc is reported to up-regulate Nrf2, thus increasing GSH synthesis and the transcription of the other target genes for antioxidant and detoxifying enzymes, including Glo-1 [ 55 , 56 , 57 , 58 ], which is the main enzyme responsible for the detoxification of the AGE precursors glyoxal and methylglyoxal, using GSH as cofactor. However, the lack of direct comparisons between mice fed with diets enriched only in zinc or spirulina does not allow us to draw definite conclusions about the added value of zinc supplementation in the formulation here tested.…”

Editorial for Special Issue “Natural Products as Potential Source of Antidiabetic Compounds”

“…McCarty et al [ 14 ] published a review addressing nutraceuticals that can be used to prevent diabetic complications, with a focus on dicarbonyl and oxidative stress. They discussed various nutraceuticals used to control oxidative and dicarbonyl stress in order to prevent diabetes-related complications.…”