title: Attenuation of insulin resistance in rats by agmatine: role of SREBP-1c, mTOR and GLUT-2.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. maha_sharawy@hotmail.com.
authors.forename: Maha H
authors.initials: MH
authors.lastname: Sharawy
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: El-Awady
authors.affiliation: Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
authors.forename: Nirmeen
authors.initials: N
authors.lastname: Megahed
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
authors.forename: Nariman M
authors.initials: NM
authors.lastname: Gameil
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D004032:Diet; D005632:Fructose; D005951:Glucose Tolerance Test; D051273:Glucose Transporter Type 2 / Q000235:genetics*; D006442:Glycated Hemoglobin / Q000032:analysis; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D047493:PPAR alpha / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D000376:Agmatine; D001786:Blood Glucose; D005632:Fructose; D051273:Glucose Transporter Type 2; D006442:Glycated Hemoglobin; D006003:Glycogen; D007328:Insulin; D008055:Lipids; D047493:PPAR alpha; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D058570:TOR Serine-Threonine Kinases; C495683:Slc2a2 protein, rat; C497389:Srebf1 protein, rat; C546845:mTOR protein, rat
keywords: Agmatine; Glucose transporter type-2; High fructose diet; Insulin resistance; Sterol regulatory element-binding protein-1c; The mammalian target of rapamycin