Exp Clin Endocrinol Diabetes 2010; 118(9): 617-624
DOI: 10.1055/s-0029-1237703
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Effects of Glycyrrhizic acid on 11 β-Hydroxysteroid Dehydrogenase (11 βHSD1 and 2) Activities and HOMA-IR in Rats at Different Treatment Periods

Y. Y. Yin1 , S. H. Ton1 , K. B. A. Kadir2
  • 1School of Sciences, Monash University, Sunway Campus, Malaysia
  • 2School of Medicine and Health Sciences, Monash University, Sunway Campus, Malaysia
Further Information

Publication History

received 03.05.2009 first decision 30.06.2009

accepted 30.06.2009

Publication Date:
08 December 2009 (online)

Abstract

Glycyrrhizic acid (GA) has been reported to inhibit postprandial blood glucose rise and 11 β-hydroxysteroid dehydrogenase 1 (11 βHSD1) activity. As not much work has been done on GA effects on 11 βHSD1 and 2 and HOMA-IR at different treatment periods, this work was conducted. 60 male Sprague Dawley rats fed ad libitum were assigned into six groups of control and treated that were given GA at different duration namely 12, 24 and 48 h. Treated and control groups were intraperitoneally administered with GA (50 mgkg−1) and saline respectively. Blood and subcutaneous (ATS) and visceral adipose tissue (ATV), abdominal (MA) and quadriceps femoris muscle (MT), liver (L) and kidney (K) were examined. HOMA-IR in GA-treated rats decreased in all groups (p<0.05). In the 12-h and 24-h treated rats, 11 βHSD1 activities decreased in all tissues (p<0.05) except MA and MT (p>0.05) in the former and ATV (p>0.05) in the latter. However, 11 βHSD1 activities decreased significantly in all tissues (p<0.05) in the 48-h treated rats. Significant decrease in 11 βHSD2 (p>0.05) activities were observed in the L of all treatment groups and K in the 24-h and 48-h treated rats (p<0.05). Histological analysis on ATS showed increase in the number of small-size adipocytes while ATV adipocytes showed shrinkage after GA administration. Increased glycogen deposition in the L was observed in the GA-administered rats in all the treatment periods. In conclusion, GA treatment showed a decrease in the HOMA-IR and both 11 βHSD1 and 2 activities in all tissues, with more profound decrease in the 48-h treated rats.

References

  • 1 Ahren B, Pacini G. Importance of quantifying insulin secretion in relation to insulin sensitivity to accurately assess beta cell function in clinical studies.  Eur J Endocrinol. 2004;  150 97-104
  • 2 Anagnostis P, Athyros VG, Tziomalos K. et al . The pathogenetic role of cortisol in the metabolic syndrome: A hypothesis.  J Clin Endocrin Metab. 2009;  doi:10.1210/jc.2009-0370
  • 3 Andrews RC, Rooyackers O, Walker BR. Effects of the 11 β-hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in men with type 2 diabetes.  J Clin Endocrinol Metab. 2003;  88 ((1)) 285-291
  • 4 Boyer R. Biochemistry laboratory: Modern theory and techniques. San Francisco: Benjamin Cummings; 2006: 272
  • 5 Bujalska IJ, Walker EA, Hewison M. et al . A switch in dehydrogenase to reductase activity of 11 β-hydroxysteroid dehydroganse type 1 upon differentiation of human omental adipose stromal cells.  J Clin Endocrinol Metab. 2002;  87 ((3)) 1205-1210
  • 6 Chapman KE, Seckl JR. 11 βHSD1, Inflammation, Metabolic disease and age-related cognitive (dys)function.  Neurochem Res. 2008;  33 624-636
  • 7 Draper N, Stewart PM. 11 β-hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action.  J Endocrinol. 2005;  186 251-271
  • 8 Gong R, Morris DJ, Brem AS. Variable expression of 11 β-hydroxysteroid dehydrogenase isoforms in vascular endothelial cells.  Steroids. 2008;  73 1187-1196
  • 9 Hammarstedtm A, Anderson CX, Rotter S. et al . The effect of PPARγ ligands on the adipose tissue in insulin resistance.  Prostaglandins Leukot Essent Fatty Acids. 2005;  73 65-75
  • 10 Harris HJ, Kotelevtsev Y, Mullins JJ. et al . Intracellular regeneration of glucocorticoids by 11 β-hydroxysteroid dehydrogenase (11 βHSD)-1 plays a key role in regulation of the hypothalamic-pituitary-adrenal axis; analysis of 11 βHSD-1 deficient mice.  Endocrinology. 2001;  142 114-120
  • 11 Inoue H, Yokota H, Makino T. et al . Bisphenol a glucuronide, a major metabolite in rat bile after liver perfusion.  Drug Metab Dispos. 2001;  29 ((8)) 1084-1087
  • 12 Isbrucker RA, Burdock GA. Risk and safety assessment on the consumption of licorice root (Glycyrrhiza sp. its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin.  Regul Toxicol Pharmacol. 2006;  46 167-192
  • 13 Jang C, Obeyesekere VR, Diley RJ. et al . Altered activity of 11 β-hydroxysteroid dehydrogenase types 1 and 2 in skeletal muscle confers metabolic protection in subjects with type 2 diabetes.  ▪. 2007;  92 ((8)) 2314-3320
  • 14 Kiernan JA. Carbohydrate histochemistry. In Histological & Histochemical Methods: Theory & Practice. 3rd edition. Butterworth Heinemann, Oxford; 1999: 213-242
  • 15 Krähenbuhl S, Hasler F, Frey BM. et al . Kinetics and dynamics of orally administered 18 β-glycyrrhetinic acid in humans.  J Clin Endocrinol Metab. 1994;  78 581-585
  • 16 Lee MJ, Fried SK, Mundt SS. et al . Depot-specific regulation of the conversion of cortisone to cortisol in human adipose tissue.  Obesity. 2008;  16 ((6)) 1178-1185
  • 17 Mahler RJ, Adler ML. Type 2 Diabetes Mellitus: Update on diagnosis, pathophysiology and treatment.  J Clin Endocrinol Metab. 1999;  84 ((4)) 1165-1171
  • 18 Masuzaki H, Paterson J, Shinyama H. et al . A transgenic model of visceral obesity and the metabolic syndrome.  Science. 2001;  294 2166-2170
  • 19 Mori Y, Murakawa Y, Okada K. et al . Effects of troglitazone on body fat distribution in type 2 diabetic patients.  Diabetes Care. 1999;  22 908-912
  • 20 Mussig K, Remer T, Haupt A. et al . 11 β-hydroxysteroid dehydrogenase 2 activity is elevated in severe obesity and negatively associated with insulin sensitivity.  Obesity. 2008;  16 ((6)) 1256-1260
  • 21 Nwe KHH, Abdul Hamid, Morat PB. et al . Differential regulation of the oxidative 11 β-hydroxysteroid dehydrogenase activity in testis and liver.  Steroids. 2000;  65 40-45
  • 22 Okuno A, Tamemoto H, Tobe K. et al . Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats.  J Clin Inves. 1998;  101 1354-1361
  • 23 Okutucu B, Dincer A, Habib Ö. et al . Comparison of five methods for determination of total plasma protein concentration.  J Biochem Biophys Methods. 2007;  70 709-711
  • 24 Ploeger B, Mensinga T, Sips A. et al . The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling.  Drug Metab Rev. 2001;  33 125-147
  • 25 Rubis B, Krozowski Z, Trzeciak WH. Arginine vasopressin stimulates 11beta-hydroxysteroid dehydrogenase type 2 expression in the mineralocorticosteroid target cells.  Mol Cell Endrocrinol. 2006;  256 17-22
  • 26 Sandeep TC, Andrew R, Homer NZM. et al . Increased in-vivo regeneration of cortisol in adipose tissue in human obesity and effects of the 11 β-hydroxysteroid dehydrogenase type 1 inhibitor carbenoxolone.  Diabetes. 2005;  54 872-879
  • 27 Schwartz MW, Kahn SE. Insulin resistance and obesity.  Nature. 1999;  402 860-861
  • 28 Shimoyama Y, Hirabyashi K, Matsumoto H. et al . Effects of glycyrrhetinic acid derivatives on hepatic and renal 11 β-hydroxysteroid dehydrogenase activities in rats.  J Pharm Pharmacol. 2003;  55 811-817
  • 29 Steward PM. 11 β- Hydroxysteroid dehydrogenase: Implications for clinical medicine.  Clin Endocrinol. 1996;  44 493-499
  • 30 Takii H, Kometani T, Nishimura T. et al . Antidiabetic effect of glycyrrhizin in genetically diabetic KK-Ay Mice.  Biol Pharm Bull. 2001;  24 484-487
  • 31 Tanahashi T, Mune T, Morita H. et al . Glycyrrhizic acid suppresses type 2 11 β-hydroxysteroid dehydrogenase expression in vivo.  J Steroid Biochem Mol Biol. 2002;  80 441-447
  • 32 Tomlinson JW, Walker EA, Bujalska IJ. et al . 11 β-hydroxysteroid dehydrogenase type 1: A tissue-specific regulator of glucocorticoid response.  Endocrine Rev. 2004;  25 ((5)) 831-866
  • 33 van Wijk JPH, Cabezas MC, de Koning EJP. et al . Rosiglitazone imporves postprandialtriglyceride and free fatty acid metabolism in type 2 diabetes.  Diabetes Care. 2005;  28 ((4)) 844-849
  • 34 Wallace TM, Levy JC, Matthew DR. use and abuse of HOMA modeling.  Diabetes Care. 2004;  27 ((6)) 1487-1495
  • 35 Whorwood CB, Donovan SJ, Flanagan D. et al . Increased glucocorticoid receptor expression in human skeletal muscle cells may contribute to the pathogenesis of the metabolic syndrome.  Diabetes. 2002;  51 1066-1075

Correspondence

Y. Y. Yin

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