Inhibition of the hepatic glucose output is responsible for the hypoglycemic effect of Crataegus aronia against type 2 diabetes mellitus in rats

Authors

  • Dalia G. Mostafa 1. Department of Medical Physiology, Faculty of Medicine, Assiut University, Assiut, Egypt; 2. Department of Medical Physiology, College of Medicine, King Khalid University, P.O.box 3340, Abha 61421, Saudi Arabia.
  • Eman F. Khaleel 1. Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt; 2. Department of Medical Physiology, College of Medicine, King Khalid University, P.O.box 3340, Abha 61421, Saudi Arabia.
  • Ghada A. Abdel-Aleem 1. Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt; 2. Department of Medical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia

Keywords:

C. aronia, insulin receptor, liver, GLUT-2, type 2 diabetes mellitus

Abstract

This study aimed to analyze the ameliorative effect of Crataegus aronia against type 2 diabetes mellitus (type 2-DM). Type 2-DM rats were treated with the extract and the changes in serum parameters (glucose, insulin, HbA1c and lipids) and hepatic parameters (oxidative stress, inflammation and mRNA levels of GLUT-2 and gluconeogenesis enzymes) were compared to those of control and untreated type 2-DM rats. Also, levels of hepatic insulin receptors 1A (IR-1A) were measured immunohistochemically and compared between groups. In type 2-DM rats, C. aronia significantly improved the oral glucose tolerance test (OGTT), lowered plasma glucose, serum lipid levels and the hepatic glycogen content. Also, it significantly lowered the levels of hepatic lipid peroxidation, tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) and enhanced the level of reduced glutathione (GSH) and increased superoxide dismutase (SOD) activity. C. aronia enhanced hepatic mRNA expression of the insulin receptor A isoform (IR-A) and glucose 6-phosphatase (G6Pase), and lowered glucose transporter-2 (GLUT-2) and glycerol kinase (GK) mRNA expression. In conclusion, C. aronia ameliorates T2DM by inhibiting hepatic glucose output.

https://doi.org/10.2298/ABS170510044M

Received: May 10, 2017; Revised: July 23, 2017; Accepted: September 18, 2017; Published online: November 13, 2017

How to cite this article: Mostafa DG, Khaleel EF, Abdel-Aleem GA. Inhibition of the hepatic glucose output is responsible for the hypoglycemic effect of Crataegus aronia against type 2 diabetes mellitus in rats. Arch Biol Sci. 2018;70(2):277-87.

Downloads

Download data is not yet available.

Author Biographies

Dalia G. Mostafa, 1. Department of Medical Physiology, Faculty of Medicine, Assiut University, Assiut, Egypt; 2. Department of Medical Physiology, College of Medicine, King Khalid University, P.O.box 3340, Abha 61421, Saudi Arabia.


Eman F. Khaleel, 1. Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt; 2. Department of Medical Physiology, College of Medicine, King Khalid University, P.O.box 3340, Abha 61421, Saudi Arabia.


References

Moller DE. Transgenic approaches to the pathogenesis of NIDDM. Diabetes. 1994;43:1394-401.

Taylor SI, Accili D, Imai Y. Insulin resistance or insulin deficiency: which is the primary cause of NIDDM? Diabetes. 1994;43:735-40.

Lin HV, Accili D. Hormonal regulation of hepatic glucose production in health and disease. Cell Metab. 2011;14:9-19.

Dufour S, Lebon V, Shulman GI, Petersen KF. Regulation of net hepatic glycogenolysis and gluconeogenesis by epinephrine in humans. Am J Physiol Endocrinol Metab. 2009;297:E231-E235.

Ader M, Bergman RN. Peripheral effects of insulin dominate suppression of fasting hepatic glucose production. Am J Physiol. 1990;258:E1020-E1032.

Lillioja S, Mott DM, Spraul M, Ferraro R, Foley JE, Ravussin E, Knowler WC, Bennett PH, Bogardus C. Insulin resistance and insulin secretory dysfunction as precursors of non insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. N Engl J Med. 1993;329:1988-92.

Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, Shulman GI. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes. 2005;54:603-8.

Brüning JC, Michael MD, Winnay JN. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell. 1998;2:559-69.

Savage DB, Zhai L, Ravikumar B. A prevalent variant in PPP1R3A impairs glycogen synthesis and reduces muscle glycogen content in humans and mice. PLoS Med. 2008;5:e27.

Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. 2006;440(7086):944-8.

Anderson EJ, Lustig ME, Boyle KE. Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest. 2009;119(3):573-81.

Nakamura S, Takamura T, Matsuzawa-Nagata N. Palmitate induces insulin resistance in H4IIEC3 hepatocytes through reactive oxygen species produced by mitochondria. J Biol Chem. 2009;284(22):14809-18.

Samuel VT, Liu ZX, Qu X, Elder BD, Bilz S, Befroy D, Romanelli AJ, Shulman GI. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem. 2004;279:32345-53. [PubMed: 15166226]

Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005;11:183-90.

Seppala-Lindroos A, Vehkavaara S, Hakkinen AM, Goto T, Westerbacka J, Sovijarvi A, Halavaara J, Yki-Jarvinen H. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab. 2002;87:3023-8.

Rubin RJ, Altman WM, Mendelson DN. Health care expenditures for people with diabetes mellitus. J Clin Endocrino Metab. 1992;78:809A-809F.

Day C. Traditional plant treatments for diabetes mellitus: pharmaceutical foods. Br J Nutr. 1998;80:5-6.

Ali-Shtayeh MS, Yaniv Z, Mahajna J. Ethnobotanical survey in the Palestinian area: a classification of the healing potential of medicinal plants. J Ethnopharmacol. 2000;73(1-2):221-32.

Al-Hallaq EK, Kasabri V, Abdalla SS, Bustanji YK, Afifi FU. Anti-obesity and antihyperglycemic effects of Crataegus aronia Extracts: In vitro and in vivo evaluations. Food Nutr Sci. 2013;4:972-83.

Shatoor AS, Said Ahmed MAA. Cardioprotective effect of Crataegus aronia syn. Azarolus (L) Aqueous Extract Against Doxorubicin-Induced Cardiotoxicity and Heart Failure in Wistar Rats. J Basic Appl Sci Res. 2014;4(2):102-14.

Mansor LS, Gonzalez ER, Cole MA, Tyler DJ, Beeson JH, Clarke K, Carr CA, Heather LC. Cardiac metabolism in a new rat model of type 2 diabetes using high-fat diet with low dose streptozotocin. Cardiovasc Diabetol. 2013;12:136.

Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res. 2005;52(4):313-20.

Friedewald WT. Estimation of concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem. 1972;18(7):499-502.

Nobert WT. Clinical guide to laboratory tests. 3rd ed. Philadelphia, PA: W.B. Saunders Co; 1995.

Lo S, Russell JC, Taylor AW. Determination of glycogen in small tissue samples. J Appl Physiol. 1970;28:234-6.

Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR. Bromobenzene-induced liver necrosis: Protective role of glutathione and evidence for 3, 4‐bromobenzene oxide as the hepatotoxic metabolite. Pharmacology. 1974;11:151‐69.

Farsi E, Ahmad M, Hor SY, Ahamed MPK, Yam MF, Asmawi MZ. Standardized extract of Ficus deltoidea stimulates insulin secretion and blocks hepatic glucose production by regulating the expression of glucose-metabolic genes in streptozotocin-induced diabetic rats. BMC Complement Altern Med. 2014;14:220.

DeFronzo RA. Pathogenesis of type 2 diabetes: metabolic metaband molecular implications for identifying diabetes genes. Diabetes Rev. 1997;5:177-269.

Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism Nature. 2001;414(13):799:806.

Leturque A, Brot-Laroche E, Le Gall M. GLUT2 mutations, translocation, and receptor function in diet sugar managing. Am J Physiol Endocrinol Metab. 2009;296:E985-E992.

Burkhardt BR, Parker MJ, Zhang YC, Song S, Wasserfall CH, Atkinson MA. Glucose transporter-2 (GLUT2) promoter mediated transgenic insulin production reduces hyperglycemia in diabetic mice. FEBS Lett. 2005; 24;579(25):5759-64.

Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest. 2000;106:171-6.

Petersen KF, Dufour S, Feng J, Befroy D, Dziura J, Dalla Man C, Cobelli C, Shulman GI. Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men. Proc Natl Acad Sci. 2006;103:18273-7.

Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2010;51:679-89.

Caldwell SH, Swerdlow RH, Khan EM. Mitochondrial abnormalities in non-alcoholic steatohepatitis. J Hepatol. 1999;31(3):430-4.

Cortez-Pinto H, Chatham J, Chacko VP, Arnold C, Rashid A, Diehl AM. Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study. JAMA. 1999;282(17):1659-64.

Hensley K, Robinson KA, Gabbita SP, Salsman S, Floyd RA. Reactive oxygen species, cell signaling, and cell injury. Free Radic Biol Med. 2000;28(10):1456-62.

Perez-Carreras M, del Hoyo P, Martın MA. Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis. Hepatology. 2003;38(4):999-1007.

Seki S, Kitada T, Yamada T, Sakaguchi H, Nakatani K, Wakasa K. In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases. J Hepatol. 2002;37(1):56-62.

Kumar D, Arya V, Bhat ZA, Khan NA, Prasad DN. The genus Crataegus: chemical and pharmacological perspectives. Rev Bras Farmacogn. 2012;22(5):1187-200.

Bahri-Sahloul R, Ammar S, Fredj RB, Saguem S, Gree S, Trotin F, Skhiri FH. Polyphenol contents and antioxidant activities of extracts from flowers of two Crataegus azarolus L. varieties. Pakistan J Biol Sci. 2009;12:660-8.

Petkov V. Plants and hypotensive, antiatheromatous and coronarodilatating action. Am J Chinese Med. 1979;3:197- 236.

Bahorun T, Gressier B, Trotin F, Brunet C, Dine T, Luyckx M, Vasseur J, Cazin M, Cazin JC, Pinkas M. Oxygen species scavenging activity of phenolic extracts from hawthorn fresh plant organs and pharmaceutical preparations. Arzneimittelforschung Drug Research. 1996;46:1086-9.

Rice-evans C. Flavonoids and isoflavones: absorption, metabolism and bioactivity. Free Radic Biol Med. 2004;36:827-8.

Orhan I, Ozcelik B, Kartal M, Ozdeveci B, Duman H. HPLC Quantification of vitexine-2-O-rhamnoside and hyperoside in three Crataegus species and their antimicrobial and antiviral activities. Chromatographia. 2007;66:S153-S157.

Wei W, Ying X, Zhang W, Chen Y, Leng A, Jiang C, Liu J. Effects of vitexin-2"-O-rhamnoside and vitexin-4"-O-glucoside on growth and oxidative stress-induced cell apoptosis of human adipose-derived stem cells. J Pharm Pharmacol. 2014;66(7):988-97.

Chang WT, Dao J, Shao ZH. Hawthorn: potential roles in cardiovascular disease. Am J Chin Med. 2005;33:1-10.

Lin CM, Huang ST, Liang YC, Lin MS, Shih CM, Chang YC, Chen TY, Chen CT. Isovitexin suppresses lipopolysaccharide-mediated inducible nitric oxide synthase through inhibition of NF-kappa B in mouse macrophages. Planta Medica. 2005;71:748-53.

Choi JS, Islam MN, Ali MY, Kim EJ, Kim YM, Jung HA. Effects of C-glycosylation on anti-diabetic, anti-Alzheimer’s disease and anti-inflammatory potential of apigenin. Food Chem Toxicol. 2014;64:27-33.

Meng S, Cao J, Feng Q, Peng J, Hu Y. Roles of chlorogenic acid on regulating glucose and lipids metabolism: A Review. Evid-Based Complement Altern Med. 2013; 2013:801457. 11.

Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozocin1061 induced diabetic rats. Comp Biochem Physiol C Toxicol Pharmacol. 2003;135C:357-64.

Coskun O, Kanter M, Korkmaz A, Oter S. Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and beta-cell damage in rat pancreas. Pharmacol Res. 2005;51:117-23.

Jeong SM, Kang MJ, Choi HN, Kim JH, Kim JI. Quercetin ameliorates hyperglycemia and dyslipidemia and improves antioxidant status in type 2 diabetic db/db mice. Nutr Res Pract. 2012;6:201-7.

Eid HM, Martineau LC, Saleem A, Muhammad A, Vallerand D, Benhaddou-Andaloussi A, Nistor L, Afshar A, Arnason JT, Haddad PS. Stimulation of AMP-activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides, active principles of the antidiabetic medicinal plant Vaccinium vitis-idaea. Mol Nutr Food Res. 2010;54:991-1003.

Dai X, Ding Y, Zhang Z, Cai X, Li Y. Quercetin and quercitrin protect against cytokineinduced injuries in RINm5F beta-cells via the mitochondrial pathway and NF-kappaB signaling. Int J Mol Med. 2013;31:265-71.

Babu PV, Liu D, Gilbert ER. Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J Nutr Biochem. 2013;24(11):1777-89.

Downloads

Published

2018-04-27

How to Cite

1.
Mostafa DG, Khaleel EF, Abdel-Aleem GA. Inhibition of the hepatic glucose output is responsible for the hypoglycemic effect of Crataegus aronia against type 2 diabetes mellitus in rats. Arch Biol Sci [Internet]. 2018Apr.27 [cited 2024Dec.22];70(2):277-8. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/1773

Issue

Section

Articles