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Abstract Title:

Reversal of Insulin Resistance in Overweight and Obese Subjects by-Resveratrol and Hesperetin Combination-Link to Dysglycemia, Blood Pressure, Dyslipidemia, and Low-Grade Inflammation.

Abstract Source:

Nutrients. 2021 Jul 11 ;13(7). Epub 2021 Jul 11. PMID: 34371884

Abstract Author(s):

Naila Rabbani, Mingzhan Xue, Martin O Weickert, Paul J Thornalley

Article Affiliation:

Naila Rabbani

Abstract:

The dietary supplement,-resveratrol and hesperetin combination (tRES-HESP), induces expression of glyoxalase 1, countering the accumulation of reactive dicarbonyl glycating agent, methylglyoxal (MG), in overweight and obese subjects. tRES-HESP produced reversal of insulin resistance, improving dysglycemia and low-grade inflammation in a randomized, double-blind, placebo-controlled crossover study. Herein, we report further analysis of study variables. MG metabolism-related variables correlated with BMI, dysglycemia, vascular inflammation, blood pressure, and dyslipidemia. With tRES-HESP treatment, plasma MG correlated negatively with endothelial independent arterial dilatation (r = -0.48,<0.05) and negatively with peripheral blood mononuclear cell (PBMC) quinone reductase activity (r = -0.68,<0.05)-a marker of the activation status of transcription factor Nrf2. For change from baseline of PBMC gene expression with tRES-HESP treatment, Glo1 expression correlated negatively with change in the oral glucose tolerance test area-under-the-curve plasma glucose (ΔAUGg) (r = -0.56,<0.05) and thioredoxin interacting protein (TXNIP) correlated positively withΔAUGg (r = 0.59,<0.05). Tumor necrosis factor-α(TNFα) correlated positively with change in fasting plasma glucose (r = 0.70,<0.001) and negatively with change in insulin sensitivity (r = -0.68,<0.01). These correlations were not present with placebo. tRES-HESP decreased low-grade inflammation, characterized by decreased expression of CCL2, COX-2, IL-8, and RAGE. Changes in CCL2, IL-8, and RAGE were intercorrelated and all correlated positively with changes in MLXIP, MAFF, MAFG, NCF1, and FTH1, and negatively with changes in HMOX1 and TKT; changes in IL-8 also correlated positively with change in COX-2. Total urinary excretion of tRES and HESP metabolites were strongly correlated. These findings suggest tRES-HESP counters MG accumulation and protein glycation, decreasing activation of the unfolded protein response and expression of TXNIP and TNFα, producing reversal of insulin resistance. tRES-HESP is suitable for further evaluation for treatment of insulin resistance and related disorders.

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