title: The ergogenic supplement β-hydroxy-β-methylbutyrate (HMB) attenuates insulin resistance through suppressing GLUT-2 in rat liver.
abstract: This study investigates the effect of the ergogenic supplement β-hydroxy-β-methylbutyrate (HMB) on insulin resistance induced by high-fructose diet (HFD) in rats. Male Sprague Dawley rats were fed 60% HFD for 12 weeks and HMB (320 mg·kg(-1)·day(-1), orally) for 4 weeks. HFD significantly increased fasting insulin, fasting glucose, glycosylated hemoglobin (HBA1C), liver glycogen content, and homeostasis model assessment of insulin resistance (HOMA-IR) index, while it decreased glucose and insulin tolerance. Furthermore, HFD significantly increased serum triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and very low density lipoprotein cholesterol (VLDL-C) levels, while it significantly decreased high density lipoprotein cholesterol (HDL-C). Moreover, HFD significantly increased mRNA expression of glucose transporter type-2 (GLUT-2), the mammalian target of rapamycin (mTOR), and sterol regulatory element-binding protein-1c (SREBP-1c) but decreased peroxisome proliferator-activated receptor-alpha (PPAR-α) in liver. Aortic relaxation to acetylcholine (ACh) was impaired and histopathology showed severe hepatic steatosis. HMB significantly increased insulin tolerance and decreased fasting insulin, HOMA-IR, HBA1C, hepatic glycogen content, serum TG, LDL-C, and VLDL-C. Additionally, HMB enhanced ACh-induced relaxation, ameliorated hepatic steatosis, and decreased mRNA expression of GLUT-2. In conclusion, HMB may attenuate insulin resistance and hepatic steatosis through inhibiting GLUT-2 in liver.
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Maha H
authors.initials: MH
authors.lastname: Sharawy
authors.affiliation: a 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: b Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Nirmeen
authors.initials: N
authors.lastname: Megahed
authors.affiliation: a 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: D000818:Animals; D004040:Dietary Carbohydrates / Q000009:adverse effects; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000503:physiopathology; D005632:Fructose / Q000009:adverse effects; D005786:Gene Expression Regulation; D018149:Glucose Intolerance / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D051273:Glucose Transporter Type 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006946:Hyperinsulinism / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D006949:Hyperlipidemias / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D047493:PPAR alpha / Q000378:metabolism; D058573:Performance-Enhancing Substances / Q000627:therapeutic use*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014631:Valerates / Q000627:therapeutic use*; D014655:Vascular Resistance
chemical_list: D004040:Dietary Carbohydrates; D051273:Glucose Transporter Type 2; D047493:PPAR alpha; D058573:Performance-Enhancing Substances; C495683:Slc2a2 protein, rat; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014631:Valerates; D005632:Fructose; C004961:beta-hydroxyisovaleric acid; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases
keywords: glucose transporter type-2; hepatic steatosis; high fructose diet; insulin resistance; régime à haute teneur en fructose; résistance à l’insuline; stéatose hépatique; transporteur du glucose de type 2; β-hydroxy-β-methylbutyrate; β-hydroxy-β-méthylbutyrate