Pyruvate-Enriched Oral Rehydration Solution Improves Glucometabolic Disorders in the Kidneys of Diabetic db/db Mice

Abstract

Diabetes is prevalent worldwide, but ideally intensive therapeutic strategy in clinical diabetes and diabetic nephropathy (DN) is still lack. Pyruvate is protective from glucometabolic disturbances and kidney dysfunction in various pathogenic insults. Present studies focused on oral pyruvate effects on diabetes status and DN with 0.35% pyruvate in pyruvate-enriched oral rehydration solution (Pyr-ORS) and 1% pyruvate as drinking water for 8 weeks, using the model of diabetic db/db mice. Both Pyr-ORS and 1% pyruvate showed comparable therapeutic effectiveness with controls of body weight and blood sugar, increases of blood insulin levels, and improvement of renal function and pathological changes. Aberrant key enzyme activities in glucometabolic pathways, AR, PK, and PDK/PDH, were also restored; indexes of oxidative stress and inflammation, NAD+/NADH ratio, and AGEs in the kidneys were mostly significantly preserved after pyruvate treatments. We concluded that oral pyruvate delayed DN progression in db/db mice and the modified Pyr-ORS formula might be an ideal novel therapeutic drink in clinical prevention and treatment of type 2 diabetes and DN.

Effects of Sodium Pyruvate on Exercise-Induced Lactic Acidosis and Exercise Performance

“…3D). As shown in previously, pyruvate activated PDH activity and promoted mitochondrial aerobic metabolism and produced more NADH and ATP 14,15 . Thus, pyruvate may increase the activity of the key rate-limiting enzymes of aerobic metabolism, such as PDH, balancing the gap between anaerobic and aerobic metabolisms during intense exercise.…”

“…Acidosis and dehydration are common events in intense soccer games, which have become critical factors that limit exercise performance 5 . Considering recent reports with pyruvate-enriched oral rehydration salt (Pyr-ORS) in effective treatments of hypoxic lactic acidosis in shock resuscitation or diabetes 14 , it is necessary to explore the effect of Pyr-ORS in intense team sports, which may enhance the oral pyruvate absorption and provide further bene ts in lactic acidosis correction and exercise performance 48 . Further research should examine the dose-effect relationship between effective blood pyruvate levels and exercise.…”

“…It mainly relies on regulating intracellular energy metabolism to reduce lactic acidosis additionally with the speci c low dissociation constant of pyruvate (pKa = 2.49) 11,12 . Studies have shown that pyruvate is a crucial intermediate of glucose metabolism and a natural inhibitor of pyruvate dehydrogenase kinase (PDK), which improves pyruvate dehydrogenase (PDH) activity and bene ts aerobic metabolism 13,14,15 . Moreover, reports have demonstrated that pyruvate can maintain glycolytic metabolism through its spontaneous reductive reaction by lactate dehydrogenase and improvement of key glycolytic enzymes 11,14 .…”

NAD+, Senolytics, or Pyruvate for Healthy Aging?

“… 3 Pyruvate also suppresses the stimulated sorbitol pathway in diseases, such as diabetes, reducing the NAD + consumption and preserving the NAD + /NADH (NAD + reduced form) ratio ( Figure 1 ). 4 Additionally, pyruvate promotes oxidative phosphorylation, reconverting NADH to NAD + in electron transport chain and producing ATP in mitochondria. The NAD + /NADH constitutes one of coenzyme redox potentials involved in a wide range of crucial enzymatic reactions.…”

“…Alternatively, exogenous pyruvate enhances energy metabolism and thus inhibits cellular senescence in addition to NAD + restoration. 4 , 66 …”