Resveratrol improves glycemic control in insulin-treated diabetic rats: participation of the hepatic territory

Abstract

BackgroundResveratrol is a natural polyphenol that has been proposed to improve glycemic control in diabetes, by mechanisms that involve improvement in insulin secretion and activity. In type 1 diabetes (T1D), in which insulin therapy is obligatory, resveratrol treatment has never been investigated. The present study aimed to evaluate resveratrol as an adjunctive agent to insulin therapy in a T1D-like experimental model.MethodsRats were rendered diabetic by streptozotocin (STZ) treatment. Twenty days later, four groups of animals were studied: non-diabetic (ND); diabetic treated with placebo (DP); diabetic treated with insulin (DI) and diabetic treated with insulin plus resveratrol (DIR). After 30 days of treatment, 24-hour urine was collected; then, blood, soleus muscle, proximal small intestine, renal cortex and liver were sampled. Specific glucose transporter proteins were analyzed (Western blotting) in each territory of interest. Solute carrier family 2 member 2 (Slc2a2), phosphoenolpyruvate carboxykinase (Pck1) and glucose-6-phosphatase catalytic subunit (G6pc) mRNAs (qPCR), glycogen storage and sirtuin 1 (SIRT1) activity were analyzed in liver.ResultsDiabetes induction increased blood glucose, plasma fructosamine concentrations, and glycosuria. Insulin therapy partially recovered the glycemic control; however, resveratrol as adjunctive therapy additionally improved glycemic control and restored plasma fructosamine concentration to values of non-diabetic rats. Resveratrol did not alter the expression of the glucose transporters GLUT2 and SGLT1 in the intestine, GLUT2 and SGLT2 in kidney and GLUT4 in soleus, suggesting that fluxes of glucose in these territories were unaltered. Differently, in liver, resveratrol promoted a reduction in Slc2a2, Pck1, and G6pc mRNAs, as well as in GLUT2 protein (P < 0.05, DIR vs. DI); besides, it increased (P < 0.01, DIR vs. DI) the hepatic glycogen content, and SIRT1 protein.ConclusionsResveratrol is able to improve glycemic control in insulin-treated T1D-like rats. This effect seems not to involve changes in glucose fluxes in the small intestine, renal proximal tubule, and soleus skeletal muscle; but to be related to several changes in the liver, where downregulation of Slc2a2/GLUT2, Pck1, and G6pc expression was observed, favoring reduction of glucose production and efflux. Besides, resveratrol increased SIRT1 nuclear protein content in liver, which may be related to the observed gene expression regulations.

Resveratrol protects podocytes against apoptosis via stimulation of autophagy in a mouse model of diabetic nephropathy

“…It is controversial whether resveratrol treatment can improve glycemic control and decrease insulin resistance. Some studies2425 found resveratrol is able to improve glycemic control and insulin sensitivity. On the contrary, resveratrol did neither affect plasma glucose concentrations, nor decrease insulin resistance in other researches2627.…”

Curcumin improves the effect of a reduced insulin dose on glycemic control and oxidative stress in streptozotocin‐diabetic rats

“…The number of studies with promising findings is increasing, especially in terms of development of efficient combined therapies of insulin or oral antidiabetic agents with natural compounds or even combinations of different natural antioxidants for supplementation in both diabetic individuals (Bolignano et al, ) and experimental models. This has resulted in the elucidation of the mechanisms of action underlying the benefits of these combinations in glycemic control and in the attenuation of the onset of multiple diabetic complications (Yonamine et al, ).…”

Insights on the Effects of Resveratrol and Some of Its Derivatives in Cancer and Autoimmunity: A Molecule with a Dual Activity

“…A following study by Kaur [108] reported the amelioration of diabetic complications, as well as the loss of β-cells, pancreatic and hepatic oxidative stress in streptozotocin-induced diabetic rats treated with 25 mg/kg of resveratrol. When co-administered with insulin, resveratrol was able to improve glycemic control in diabetic rats, lowering the blood glucose to the levels reported in non-diabetic rats and cutting down glycosuria [109].…”