Beneficial effects of combined resveratrol and metformin therapy in treating diet‐induced insulin resistance

Abstract

The polyphenol compound resveratrol (RSV) has attracted attention due to its reputed beneficial effects on insulin sensitivity. Our lab has previously identified protective effects of RSV against the development of type 2 diabetes in rats. These effects occurred in a manner similar to thiazolidinedione's (TZDs), a class of insulin sensitizing drugs. TZDs are commonly prescribed in combination with metformin (MET) and thus we sought to examine the combined effects of RSV and MET in treating insulin resistance. Male C57BL6 mice were fed a low‐ (LFD; 10% Kcal from fat) or high‐fat diet (HFD; 60% Kcal from fat) for 9 weeks to induce glucose and insulin intolerance. HFD mice were then assigned to control (HFD), MET (231.28 ± 12.24 mg/kg/day), RSV (93.68 ± 3.51 mg/kg/day), or combined (COM; MET 232.01 ± 17.12 mg/kg/day and RSV 92.77 ± 6.92 mg/kg/day) treatment groups. Changes in glucose and insulin tolerance and tissue‐specific insulin signaling were measured 4 weeks post‐treatment. RSV or MET alone did not have beneficial effects on glucose tolerance, although MET significantly improved insulin tolerance compared to HFD. Glucose and insulin tolerance were significantly improved in COM compared to HFD and this was mirrored by enhanced insulin‐stimulated AKT phosphorylation in triceps muscle and inguinal subcutaneous adipose tissue in COM compared to HFD mice. Improvements with COM treatment were not explained by differences in body weight, adiposity, or markers of adipose tissue inflammation. In summary, this study provides evidence of beneficial effects of combined RSV and MET therapy in treating impairments in glucose homeostasis.

The effects of trans-resveratrol on insulin resistance, inflammation, and microbiota in men with the metabolic syndrome: a pilot randomized, placebo controlled clinical trial

“…It has been stated that there is sufficient information from rodent studies that RES has the capacity to improve insulin sensitivity and reduce blood glucose levels accompanied by modulation of inflammatory response to various stimuli. RES has been used in conjunction with metformin to improve insulin sensitivity and glucose homeostasis in pre-diabetic subjects [38]. However, studies in humans are fragmentary and generally inadequate [39].…”

Epinephrine responsiveness is reduced in livers from trained mice

“…15596018; ThermoFisher Scientific) and RNA was extracted using Bio Basic EZ-10 Spin Column Total RNA Miniprep Super Kits (cat no. BS784; Bio Basic) as described previously (Frendo-Cumbo et al, 2016;Peppler, Townsend, Knuth, Foster, & Wright, 2018;Townsend et al, 2019). Synthesis of cDNA was completed using Superscript II (cat no.…”

Exploring the Comparative Efficacy of Metformin and Resveratrol in the Management of Diabetes-Associated Complications: A Systematic Review of Preclinical Studies

“…A similar trend was found in 3T3L1 adipocytes In mice, the two lower doses of metformin exerted no independent effect but, when combined with resveratrol-HMB, both low-dose and very low-dose metformin improved insulin sensitivity (HOMA(IR)), plasma insulin levels, and insulin tolerance test response to a level comparable with that found for high-dose metformin. Additionally, the metformin-resveratrol-HMB combination decreased visceral fat and liver weight in mice Fu et al 2015 [59] High fat diet-fed (HFD) male C57BL/6 mice received a combination of leucine (24 g/kg diet), resveratrol (12.5 mg/kg/diet) and metformin (0.05-0.5 g/kg diet) for 6 weeks The combination of leucine, metformin, and resveratrol was more effective than the use of metformin as a monotherapy in improving glucose tolerance Duarte-Vázquez et al 2016 [22] Type 2 diabetic (db/db) mice received resveratrol (20 mg/kg/day), metformin (150 mg/kg/day) and combined metformin/resveratrol therapy for 5 weeks Data clearly showed that combined metformin/resveratrol treatment reduced obesity, glucose, and triglyceride levels, as well as improving renal function and partially improving liver function in diabetic mice Frendo-Cumbo et al 2016 [23] Male C57BL6 mice fed HFD were given metformin (231 mg/kg/day), resveratrol (93 mg/kg/day), or combined (metformin 232.01 ± 17.12 mg/kg/day and resveratrol 92 mg/kg/day) treatment groups for 4 weeks Treatment with each compound alone did not have beneficial effects on glucose tolerance, although metformin significantly improved insulin tolerance. Glucose and insulin tolerance were significantly improved in the combination treatment.…”

“…Resveratrol (PubChem CID: 445154) can be found in several food sources including grapes and red wine [21]. Interestingly, experimental evidence reporting on the comparative or combination use of metformin (PubChem CID: 4091) with well-known bioactive compounds like resveratrol has become of great interest [22][23][24][25][26][27]. Although metformin is a commonly used antidiabetic drug, information on its comparative or combination use with resveratrol has not been assessed to understand the potential synergistic or combination advantages of such a therapy in managing metabolic complications.…”