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Supplementation of scopoletin improves insulin sensitivity by attenuating the derangements of insulin signaling through AMPK

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Abstract

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.

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Abbreviations

T2D:

Type 2 diabetes

HFFD:

High fat, high fructose diet

AMPK:

5′-AMP activated protein kinase

SPL:

Scopoletin

AICAR:

5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside

TC:

Total cholesterol

TG:

Triglycerides

HDL-C:

High density lipoprotein cholesterol

LDL-C:

Low density lipoprotein cholesterol

VLDL-C:

Very low density lipoprotein cholesterol

TBARS:

Thiobarbituric acid reactive substances

LHP:

Lipid hydroperoxides

PC:

Protein carbonyl

SOD:

Superoxide dismutase

CAT:

Catalase

GPx:

Glutathione peroxidase

IRS:

Insulin receptor substrate

PI3K:

Phosphatidyl inositol 3 kinase

Akt/PKB:

Protein kinase B

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Acknowledgements

This work was supported by Department of Science and Technology, Women Scientists Scheme-A, New Delhi, India under “Disha programme for women in Science” (SR/WOS-A/LS-1170/2014). The authors wish to thank DST-FIST and UGC-SAP for the facilities developed in the Department of Biochemistry and Biotechnology, Annamalai University for executing the present study.

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  1. Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Chidambaram, Tamil Nadu, 608002, India

    Kalaivanan Kalpana, Chandrasekaran Sathiya Priya, Nanda Dipti, Ramachandran Vidhya & Carani Venkatraman Anuradha

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  1. Kalaivanan Kalpana
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  2. Chandrasekaran Sathiya Priya
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Correspondence to Carani Venkatraman Anuradha.

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Experimental procedures were approved by the Institutional Animal Ethics Committee (IAEC), Annamalai University, and conducted according to the guidelines by the committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) (Proposal No. 1091).

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Kalpana, K., Sathiya Priya, C., Dipti, N. et al. Supplementation of scopoletin improves insulin sensitivity by attenuating the derangements of insulin signaling through AMPK. Mol Cell Biochem 453, 65–78 (2019). https://doi.org/10.1007/s11010-018-3432-7

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