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Attenuation of insulin resistance in rats by agmatine: role of SREBP-1c, mTOR and GLUT-2

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Abstract

Insulin resistance is a serious health condition worldwide; however, its exact mechanisms are still unclear. This study investigates agmatine (AGM; an endogenous metabolite of l-arginine) effects on insulin resistance induced by high fructose diet (HFD) in rats and the possible involved mechanisms. Sprague Dawley rats were fed 60 % HFD for 12 weeks, and AGM (10 mg/kg/day, orally) was given from week 9 to 12. AGM significantly reduced HFD-induced elevation in fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR) index and liver glycogen content from 3.44-, 3.62- and 2.07- to 2.59-, 2.78- and 1.3-fold, respectively, compared to the control group, while it increased HFD-induced reduction in glucose tolerance. Additionally, AGM significantly decreased HFD-induced elevation in serum triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol levels from 3.18-, 2.97- and 4.75- to 1.25-, 1.25- and 1.07-fold, respectively, compared to control group. Conversely, AGM had no significant effect on HFD-induced changes in fasting glucose, glycosylated hemoglobin, insulin tolerance and high density lipoprotein cholesterol. Furthermore, AGM significantly reduced HFD-induced elevation in mRNA expression of glucose transporter type-2 (GLUT-2), mammalian target of rapamycin (mTOR) and sterol regulatory element-binding protein-1c (SREBP-1c) without affecting that of peroxisome proliferator-activated receptor-alpha (PPAR-α) in the liver. Additionally, AGM enhanced ACh-induced aortic relaxation and attenuated liver steatosis induced by HFD. In conclusion, AGM may have a therapeutic potential in insulin resistance through suppressing SREBP-1c, mTOR and GLUT-2 in liver.

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Abbreviations

AGM:

Agmatine

GLUT-2:

Glucose transporter type-2

HFD:

High fructose diet

HOMA-IR:

Homeostasis model assessment of insulin resistance

mTOR:

The mammalian target of rapamycin

PPAR-α:

Peroxisome proliferator-activated receptor-alpha

SREBP-1c:

Sterol regulatory element-binding protein-1c

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Acknowledgments

The authors acknowledge Dr. Mahmoud Gabr and the staff members of the Research Department, Urology and Nephrology Center, Mansoura University, Egypt, for kindly sharing the facilities of their laboratory and their helpful support.

Conflict of interest

None declared.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt

    Maha H. Sharawy, Mohammed S. El-Awady & Nariman M. Gameil

  2. Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt

    Nirmeen Megahed

Authors
  1. Maha H. Sharawy
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  2. Mohammed S. El-Awady
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  3. Nirmeen Megahed
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  4. Nariman M. Gameil
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Correspondence to Maha H. Sharawy.

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Sharawy, M.H., El-Awady, M.S., Megahed, N. et al. Attenuation of insulin resistance in rats by agmatine: role of SREBP-1c, mTOR and GLUT-2. Naunyn-Schmiedeberg's Arch Pharmacol 389, 45–56 (2016). https://doi.org/10.1007/s00210-015-1174-6

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