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Four weeks exercise training enhanced the hepatic insulin sensitivity in high fat- and high carbohydrate-diet fed hyperinsulinemic rats

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Abstract

Aim

Hyperinsulinemia is considered the primary defect underlying the development of type 2 diabetes. The liver is essential for the regular glucose homeostasis. In this study, we examined the effect of physical training on the insulin signaling, oxidative stress enzymes and Glucose-6-phosphatase(G6Pase) activity in the liver of Wistar rats.

Methods

Adult male Wistar rats were divided into Control diet group(C), High carbohydrate diet(HCD), High fat diet(HFD), HCD and HFD with training(HCD Ex & HFD Ex). HFD Ex and HCD Ex were trained on a small animal treadmill running at 20 m/min for 30 min, 5 days/wk. The present work investigated the effect of training on hepatic insulin receptor(InsR) signaling events, oxidative stress marker expressions and G6Pase activity in hyperinsulinemic rats.

Results

High carbohydrate and fat feeding led to hyperinsulinemic status with increased hepatic G6Pase activity and impaired phosphorylation of insulin receptor substrate 1(IRS1) and reduced expression of antioxidant enzymes.Training significantly reduced hepatic G6Pase activity, upregulated phosphoinositide 3 kinase(PI3K) docking site phosphorylation and downregulated the negative IRS1 phosphorylations thereby increasing the glucose transporter(GLUT) expressions (aa(P < 0.001) when compared to HFD, b(P < 0.01),bb (P < 0.001 when compared to HCD). Anti oxidant enzymes like CAT, SOD, eNOS expression were increased with reduction in the expression of inflammatory enzymes like TNF-α and COX-2 (*(P < 0.05),**(P < 0.01),***(P < 0.001) when compared to control, †(P < 0.05),††(P < 0.01),†††(P < 0.001) when compared to HFD and HCD).

Conclusion

Thus, our study shows that four weeks training enhanced the hepatic insulin sensitivity in high fat and high carbohydrate-diet fed hyperinsulinemic rats.

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Acknowledgements

The authors thank Mr Sreerenj and faculties of Department of Health Sciences, University of Calicut for allowing the use of department facilities. We also thank the MIMSRF Lab manager Mr Varun and assistant Mrs Mahishiya for their timely help.

Funding

This work is supported by funding from DST SERB, Govt. of India (ECR/2015/000158) and MIMS Research Foundation, Calicut, Kerala.

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Authors and Affiliations

  1. MIMS Research Foundation, Mankavu P.O., Calicut, Kerala, 673007, India

    Anu Joseph, S. Parvathy, Koyikkal Karthikeya Varma & Aiswarya Nandakumar

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Contributions

AJ: Conceptualization, Methodology, Writing- Reviewing and Editing, PS.: Methodology, Investigation, Validation Writing – Original Draft, KKV: Supervision, Writing – Review & Editing. AN- Standardisation All authors have read and approved the final manuscript.

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Correspondence to Anu Joseph.

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All animal care and procedures were in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals by the Committee for the Purpose of Control And Supervision of Experiments on Animals (CPCSEA), Govt. Of India and was approved by MIMS Research Foundation Ethics Committee.

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Joseph, A., Parvathy, S., Varma, K.K. et al. Four weeks exercise training enhanced the hepatic insulin sensitivity in high fat- and high carbohydrate-diet fed hyperinsulinemic rats. J Diabetes Metab Disord 19, 1583–1592 (2020). https://doi.org/10.1007/s40200-020-00694-y

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