Scopoletin (SPL), a phenolic coumarin, is reported to regulate glucose metabolism. This study is initiated to substantiate the action of SPL on the regulation of insulin signaling in insulin resistant RIN5f cells and high fat, high fructose diet (HFFD)-fed rat model. Adult male Sprague Dawley rats were fed HFFD for 45 days to induce type 2 diabetes and then treated or untreated with SPL for the next 45 days. The levels of glucose, insulin, lipid profile, oxidative stress markers along with insulin signaling and AMPK protein expressions were examined at the end of 90 days. SPL lowered the levels of plasma glucose, insulin, and lipids which were increased in HFFD-fed rats. HFFD intake suppressed the activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase; however, they were reversed by SPL supplementation, which reduced TBARS, lipid hydroperoxide, and protein carbonyl levels both in plasma and pancreas. SPL supplementation significantly activated insulin receptor substrate 1 (IRS1), phosphatidyl inositol 3-kinase (PI3K), and protein kinase B (Akt) phosphorylation which was suppressed in HFFD rats due to lipotoxicity. Moreover, SPL significantly activated AMPK and enhanced the association of IRS1-PI3K-Akt compared to the control group. The results revealed that SPL alleviated T2D induced by HFFD by escalating the antioxidant levels and through insulin signaling regulation. We conclude that SPL can improve insulin signaling through AMPK, thereby confirming the role of SPL as an AMPK activator.
Abstract
Introduction: Polycystic ovary syndrome (PCOS) is an endocrine, reproductive and metabolic disorder and a major cause of infertility in women. Testosterone propionate (TP) is used to induce PCOS in rats. High calorie diet causes metabolic changes, oxidative stress and PCOS. Sitagliptin (STG) is an inhibitor of dipeptide peptidase (DPP) 4 enzyme used in the treatment of type 2 diabetes. Objective: The aim of the study is to investigate the effect of high fat, high fructose diet (HFFD) on TP induced PCOS rats and the role of STG on oxidative stress and inflammation in PCOS. Materials and methods: PCOS was induced by administration of TP to normal pellet and HFFD fed rats for 43 days. STG (i.p.) was given for the last 15 days to both groups of rats. Vaginal smear, parameters of oxidative stress, antioxidants and inflammation (TNF-α and IL-6) in ovary were analyzed. Results: Vaginal smear from TP rats consisted of persistent leucocytes, a characteristic of PCOS. All the TP administered rats registered significanty elevated levels of glucose, lipids, oxidative stress and inflammatory markers, and reduced levels of antioxidants compared to CON rats. STG treatment to PCOS rats reduced hyperglycemia and hyperlipidemia, oxidative stress and inflammation and improved estrus cycle. Conclusion: High energy diet aggravated TP-induced changes in oxidative stress and inflammatory cytokines in ovary. STG recuperated the changes induced by TP, suggesting that STG holds potential for PCOS management.
MicroRNAs (miRNAs) are small, endogenous, non-coding, single stranded RNAs which play a role in the regulation of gene expression and function. Therefore, the analysis of differentially expressed miRNAs are of great importance in disease diagnosis. This study is focussed on the differential expression of miRNAs in serum of PCOS subjects compared to control and their correlation with metabolic and endocrine parameters. Anthropometry, hormone concentrations and biochemical characteristics were measured in healthy (n = 20) and PCOS (n = 20) subjects. MiR-24, miR-29a and miR-502-3p were determined in serum by quantitative RT-PCR. The levels of miR-24 was significantly decreased in PCOS subjects (P = 0.00) compared to control. No significant difference was observed in the levels of miR-29a and miR-502-3p in PCOS and control subjects. MiR-24 showed significant inverse correlation with BMI, glucose, insulin, FIRI, HOMA, LH, testosterone, TG, and LH:FSH ratio whereas HDL levels showed significant positive association with miR-24 and miR-29a. LH showed significant negative association with miR-29a. No correlation was observed between the expression of miR-502-3p with any of the studied parameters. The receiver operating characteristic curve for miR-24 alone showed a significant discriminative capacity. The study suggests that serum miR-24 analysis in PCOS patients could be of diagnostic value that can be used as a biomarker for PCOS.
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