Preventative effects of resveratrol and estradiol on streptozotocin-induced diabetes in ovariectomized mice and the related mechanisms

Abstract

Resveratrol, a non-flavonoid polyphenolic compound, is structurally and functionally similar to estrogen and has drawn great attention for its potentially beneficial effects on diabetes. However, it is not known whether it shares the same protective effect against diabetes as estrogen and the underlying mechanisms. The aim of the present study was to investigate the protective effects of phytoestrogen resveratrol and exogenous 17β-estradiol against streptozotocin (STZ)-induced type 1 diabetes. Female mice were ovariectomized (OVX) and chronically injected with different concentrations of resveratrol (0.1, 1 or 10 mg/kg) and 17β-estradiol (0.01, 0.1 or 1 mg/kg) subcutaneously for 4 weeks, and the levels of blood glucose, plasma insulin, plasma antioxidant capacity, the changes of pancreatic islet cells and the expressions of glucose transporter 4 (GLUT4), insulin receptor substrate 1 (IRS-1) and phosphorylation of extracellular signal-regulated kinase (p-ERK) were detected. Resveratrol and 17β-estradiol significantly inhibited the increase of the blood glucose level and the rise of plasma malondialdehyde in STZ-induced diabetic mice, improved the levels of plasma antioxidant capacity and plasma insulin, protected the pancreatic islet cells, and increased the expressions of GLUT4 and IRS-1, but decreased p-ERK expression in skeletal muscle and myocardial tissue. The results suggest that resveratrol or 17β-estradiol shows obvious protection against STZ-induced diabetes in OVX mice, the mechanisms probably involve their ameliorating antioxidant activities and islet function, promoting muscle glucose uptake and inhibiting the expression of p-ERK.

Efficacy and Safety of Resveratrol in Type 1 Diabetes Patients: A Two-Month Preliminary Exploratory Trial

“…The major factors contributing to T1D-related hyperglycemia are reduced or no insulin secretion, decreased glucose utilization by the peripheral tissue, and increased glucose production. Resveratrol has been shown to improve all of the factors mentioned above in the setting of T1D, as reported by previous preclinical studies [18][19][20][21][22]. In this current study, we also observed that resveratrol treatment significantly reduced FBS and HbA1c in T1D patients.…”

In Vivo Hypoglycemic Effects, Potential Mechanisms and LC-MS/MS Analysis of Dendropanax Trifidus Sap Extract

“…It was previously shown that estradiol injections reduced fasting blood GLU levels in non-obese C57BL/6N mice with short-term ovariectomy, while AMPK was activated and gluconeogenic gene expression was reduced in liver tissues [31]. A 4-week subcutaneous injection of estradiol to ovariectomized female mice with STZinduced type 1 diabetes significantly suppressed blood GLU level and increased plasma insulin, suggesting protective effects of estradiol against STZ-induced diabetes [32]. Besides estradiol, various components were identified from DT sap, such as caryophyllene oxide, curcumene, 3, 5-di-tert-butyl-4-hydroxybenzaldehyde, trenbolone, farnesol, dienogest, 2-Hydroxyestradiol, isotretinoin, linoleic acid and costunolide (Table 1).…”

Recent Review on Role of Resveratrol in Diabetes and its Complication

“…Resveratrol has shown in interfering with estrogen receptors, which is one way, has an indirect relation with diabetes (Li et al, 2018) . Has told above resveratrol effects in diabetes has already been researched in rats, which are made diabetic by streptozocin.…”

“…In a few studies, resveratrol has also shown to act on insulin resistant and increase insulin levels. Table 2 Resveratrol and 17β-estradiol 17β-Estradiol action in diabetes has already been proved along with resveratrol as discussed in various diabetic animal models (Catanuto et al, 2009;Li et al, 2018), in diabetic humans, and also in rats with Type 1 D. But estrogen has some interference in studies, so its effect was removed by removing both ovaries. Various parameters such as T-AOC (plasma total antioxidant capacity), FPI (Fasting Plasma insulin level), etc... were studied.…”