Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 392, Issue 1, pp 103–116 | Cite as

Sodium acetate improves disrupted glucoregulation and hepatic triglyceride content in insulin-resistant female rats: involvement of adenosine deaminase and dipeptidyl peptidase-4 activities

  • Tolulope Eniola Omolekulo
  • Olugbenga Samuel Michael
  • Lawrence Aderemi OlatunjiEmail author
Original Article


Combined oral contraceptive (COC) treatment has been shown to be associated with glucose deregulation and increased triglyceride levels, but the mechanisms are elusive. Soluble dipeptidyl peptidase-4 (sDPP-4) and adenosine deaminase (ADA) are involved in the initiation and/or progression of cardiometabolic disorders. We therefore, hypothesized that increased DPP-4 and ADA activities are involved in glucose deregulation and hepatic triglyceride accumulation induced by COC treatment. This study also investigated whether short-chain fatty acid, acetate, would protect against COC-induced dysmetabolic effects. Female Wistar rats received (p.o.) vehicle and COC (1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel) with or without sodium acetate (ACE; 200 mg) for 8 weeks. Treatment with COC led to increased plasma triglyceride-glucose index, 1-h postload glucose response, insulin, free fatty acid, insulin resistance, and impaired glucose tolerance. COC treatment also resulted in increased plasma and hepatic triglycerides (TG), TG/HDL-cholesterol ratio, malondialdehyde, uric acid, lactate dehydrogenase, DPP-4, ADA, and xanthine oxidase (XO) activities. On the other hand, COC led to reduction in nitric oxide level. However, ACE significantly ameliorated the alterations induced by COC treatment, but XO activity remains elevated during COC treatment. This result also demonstrates that increased DPP-4 and ADA activities are at least in part involved in glucose deregulation and hepatic TG accumulation induced by COC treatment. Therefore, sodium acetate would impact positively on cardiometabolic disorders, at least in part, by inhibition of DPP-4 and ADA activities.


Adenosine deaminase Combined oral contraceptive Dipeptidyl peptidase-4 Hepatic insulin resistance 



This research was done without specific grant from any funding agencies in the public, commercial or not-for-profit sectors. The authors appreciate the technical support from the HOPE Cardiometabolic Research Team, Ilorin, Nigeria.

Author contribution statement

OLA conceived and designed the research. OTE conducted experiments. OLA contributed new reagents and analytical kits. OTE, MOS and OLA analyzed and interpreted data. OLA, OTE and MOS drafted the manuscript. OTE, MOS, and OLA read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. Adiels M, Westerbacka J, Soro-Paavonen A, Häkkinen AM, Vehkavaara S, Caslake MJ, Packard C, Olofsson SO, Yki-Järvinen H, Taskinen MR, Borén J (2007) Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance. Diabetologia 50:2356–2365CrossRefGoogle Scholar
  2. Agius L (2010) Physiological control of liver glycogen metabolism: lessons from novel glycogen phosphorylase inhibitors. Mini-Rev Med Chem 10:1175–1187CrossRefGoogle Scholar
  3. Anstee QM, Targher G, Day CP (2013) Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 10:330–344CrossRefGoogle Scholar
  4. Balaban YH, Korkusuz P, Simsek H, Gokcan H, Gedikoglu G, Pinar A, Hascelik G, Asan E, Hamaloglu E, Tatar G (2007) Dipeptidyl peptidase IV (DDP IV) in NASH patients. Ann Hepatol 6:242–250Google Scholar
  5. Barreira da Silva R, Laird ME, Yatim N, Fiette L, Ingersoll MA, Albert ML (2015) Dipeptidyl peptidase 4 inhibition enhances lymphocyte trafficking, improving both naturally occurring tumor immunity and immunotherapy. Nat Immunol 16:850–858CrossRefGoogle Scholar
  6. Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S (2005) Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 42:44–52CrossRefGoogle Scholar
  7. Bianchi C, Miccoli R, Trombetta M, Giorgino F, Frontoni S, Faloia E, Marchesini G, Dolci MA, Cavalot F, Cavallo G, Leonetti F, Bonadonna RC, del Prato S, GENFIEV Investigators (2013) Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired β-cell function, insulin resistance, and worse cardiovascular risk profile: the GENFIEV study. J Clin Endocrinol Metab 98:2100–2105CrossRefGoogle Scholar
  8. Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, Muir AI, Wigglesworth MJ, Kinghorn I, Fraser NJ, Pike NB, Strum JC, Steplewski KM, Murdock PR, Holder JC, Marshall FH, Szekeres PG, Wilson S, Ignar DM, Foord SM, Wise A, Dowell SJ (2003) The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 278(13):11312–11319CrossRefGoogle Scholar
  9. Choi SH, Leem J, Park S, Lee CK, Park KG, Lee IK (2017) Gemigliptin ameliorates Western-diet-induced metabolic syndrome in mice. Can J Physiol Pharmacol 95(2):129–139CrossRefGoogle Scholar
  10. Cristalli G, Costanzi S, Lambertucci C, Lupidi G, Vittori S, Volpini R et al (2001) Adenosine deaminase: functional implications and different classes of inhibitors. Med Res Rev 21:105–128CrossRefGoogle Scholar
  11. Cusi K (2009) Role of insulin resistance and lipotoxicity in nonalcoholic steatohepatitis. Clin Liver Dis 13:545–563CrossRefGoogle Scholar
  12. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ (2005) Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115:1343–1351CrossRefGoogle Scholar
  13. Elbers JM, de Roo GW, Popp-Snijders C, Nicolaas-Merkus A, Westerveen E, Joenje BW et al (1999) Effects of administration of 17beta-oestradiol on serum leptin levels in healthy postmenopausal women. Clin Endocrinol 51:449–454CrossRefGoogle Scholar
  14. Firneisz G, Varga T, Lengyel G, Fehér J, Ghyczy D, Wichmann B et al (2010) Serum dipeptidyl peptidase-4 activity in insulin resistant patients with non-alcoholic fatty liver disease: a novel liver disease biomarker. PLoS One 5:e12226CrossRefGoogle Scholar
  15. Fonseca VA (2010) Early identification and treatment of insulin resistance: impact on subsequent prediabetes and type 2 diabetes. Clin Cornerstone 8:S7–S18Google Scholar
  16. Freeland KR, Wolever TM (2010) Acute effects of intravenous and rectal acetate on glucagon-like peptide-1, peptide YY, ghrelin, adiponectin and tumour necrosis factor-alpha. Br J Nutr 103(3):460–466CrossRefGoogle Scholar
  17. Frost G, Sleeth ML, Sahuri-Arisoylu M, Lizarbe B, Cerdan S, Brody L, Anastasovska J, Ghourab S, Hankir M, Zhang S, Carling D, Swann JR, Gibson G, Viardot A, Morrison D, Louise Thomas E, Bell JD (2014) The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun 5:3611CrossRefGoogle Scholar
  18. Fuller M, Priyadarshini M, Gibbons SM, Angueira AR, Brodsky M, Hayes MG, Kovatcheva-Datchary P, Bäckhed F, Gilbert JA, Lowe WL Jr, Layden BT (2015) The short-chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis. Am J Physiol Endocrinol Metab 309:E840–E851CrossRefGoogle Scholar
  19. Gao Q, Horvath TL (2008) Cross-talk between estrogen and leptin signaling in the hypothalamus. Am J Physiol Endocrinol Metab 294:E817–E826CrossRefGoogle Scholar
  20. Ginsberg HN, Zhang YL, Hernandez-Ono A (2005) Regulation of plasma triglycerides in insulin resistance and diabetes. Arch Med Res 36(3):232–240CrossRefGoogle Scholar
  21. Godsland IF, Crook D, Simpson R, Proudler T, Felton C, Lees B, Anyaoku V, Devenport M, Wynn V (1990) The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism. N Engl J Med 323(20):1375–1381CrossRefGoogle Scholar
  22. Guerrero-Romero F, Simental-Mendia LE, Gonzalez-Ortiz M, Martínez-Abundis E, Ramos-Zavala MG, Hernández-González SO et al (2010) The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic hyperinsulinemic clamp. J Clin Endocrinol Metab 95:3347–3351CrossRefGoogle Scholar
  23. Haarbo J, Marslew U, Gotfredsen A, Christiansen C (1991) Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause. Metabolism 40:1323–1326CrossRefGoogle Scholar
  24. Hong YH, Nishimura Y, Hishikawa D, Tsuzuki H, Miyahara H, Gotoh C, Choi KC, Feng DD, Chen C, Lee HG, Katoh K, Roh SG, Sasaki S (2005) Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology 146:5092–5099CrossRefGoogle Scholar
  25. Hwang JH, Stein DT, Barzilai N, Cui MH, Tonelli J, Kishore P, Hawkins M (2007) Increased intrahepatic triglyceride is associated with peripheral insulin resistance: in vivo MR imaging and spectroscopy studies. Am J Physiol Endocrinol Metab 293:E1663–E1669CrossRefGoogle Scholar
  26. Itou M, Kawaguchi T, Taniguchi E, Sata M (2013) Dipeptidyl peptidase-4: a key player in chronic liver disease. World J Gastroenterol 19(15):2298–2306CrossRefGoogle Scholar
  27. Johnston CS, Kim CM, Buller AJ (2004) Vinegar improves insulin sensitivity to a high-carbohydrate meal in subjects with insulin resistance or type 2 diabetes. Diabetes Care 27(1):281–282CrossRefGoogle Scholar
  28. Kelley EE, Khoo NK, Hundley NJ, Malik UZ, Freeman BA, Tarpey MM (2010) Hydrogen peroxide is the major oxidant product of xanthine oxidase. Free Radic Biol Med 48:493–498CrossRefGoogle Scholar
  29. Khemka VK, Bagchi D, Ghosh A, Sen O, Bir A, Chakrabarti S, Banerjee A (2013) Raised serum adenosine deaminase level in nonobese type 2 diabetes mellitus. Sci World J 2013:404320. CrossRefGoogle Scholar
  30. Kondo T, Kishi M, Fushimi T, Kaga T (2009) Acetic acid upregulates the expression of genes for fatty acid oxidation enzymes in liver to suppress body fat accumulation. J Agric Food Chem 57(13):5982–5986CrossRefGoogle Scholar
  31. Kurtul N, Pence S, Akarsu E, Kocoglu H, Aksoy Y, Aksoy H (2004) Adenosine deaminase activity in the serum of type 2 diabetic patients. Acta Med (Hradec Kralove) 47:33–35Google Scholar
  32. Lambeir AM, Durinx C, Scharpe S, De Meester I (2003) Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci 40:209–294CrossRefGoogle Scholar
  33. Lamers D, Famulla S, Wronkowitz N, Hartwig S, Lehr S, Ouwens DM Hartwig S, Lehr S, Ouwens DM, Eckardt K, Kaufman JM, Ryden M, Muller S, Hanisch FG, Ruige J, Arner P, Sell H, Eckel J (2011) Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes 60: 1917–1925Google Scholar
  34. Layden BT, Yalamanchi SK, Wolever TMS, Dunaif A, Lowe WL Jr (2012) Negative association of acetate with visceral adipose tissue and insulin levels. Diabetes Metab Syndr Obes 5:49–55CrossRefGoogle Scholar
  35. Layden BT, Angueira AR, Brodsky M, Durai V, Lowe WL Jr (2013) Short chain fatty acids and their receptors: new metabolic targets. Trans Res 161:131–140CrossRefGoogle Scholar
  36. Lewis GF, Carpentier A, Adeli K, Giacca A (2002) Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 23(2):201–229CrossRefGoogle Scholar
  37. Lillioja S, Mott DM, Spraul M, Ferraro R, Foley JE, Ravussin E (1993) Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. N Engl J Med 329:1988–1992CrossRefGoogle Scholar
  38. Mandal AK, Mount DB (2015) The molecular physiology of uric acid homeostasis. Annu Rev Physiol 77:323e345CrossRefGoogle Scholar
  39. Mannucci E, Pala L, Ciani S, Bardini G, Pezzatini A, Sposato I, Cremasco F, Ognibene A, Rotella CM (2005) Hyperglycaemia increases dipeptidyl peptidaseIV activity in diabetes mellitus. Diabetologia 48:1168–1172CrossRefGoogle Scholar
  40. Marguet D, Baggio L, Kobayashi T, Bernard AM, Pierres M, Nielsen PF, Ribel U, Watanabe T, Drucker DJ, Wagtmann N (2000) Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc Natl Acad Sci U S A 97:6874–6879CrossRefGoogle Scholar
  41. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D et al (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461:1282–1286CrossRefGoogle Scholar
  42. Matthaei S, Stumvoll M, Kellerer M, Haring HU (2000) Pathophysiology and pharmacological treatment of insulin resistance. Endocr Rev 21:585–618Google Scholar
  43. McCullough AJ (2004) The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis 8:521–533CrossRefGoogle Scholar
  44. McLaughlin T, Reaven G, Abbasi F, Lamendola C, Saad M, Waters D, Simon J, Krauss RM (2005) Is there a simple way to identify insulin-resistant individuals at increased risk of cardiovascular disease? Am J Cardiol 96:399–404CrossRefGoogle Scholar
  45. Migoya E, Larson P, Bergman A, Miller J, Johnson-Levonas AO, Lasseter KC, Wagner JA (2011) Sitagliptin, a dipeptidyl peptidase-4 inhibitor, does not affect the pharmacokinetics of ethinyl estradiol or norethindrone in healthy female subjects. J Clin Pharmacol 51:1319–1325CrossRefGoogle Scholar
  46. Miyazaki M, Kato M, Tanaka K, Tanaka M, Kohjima M, Nakamura K et al (2012) Increased hepatic expression of dipeptidyl peptidase-4 in nonalcoholic fatty liver disease and its association with insulin resistance and glucose metabolism. Mol Med Rep 5:729–733Google Scholar
  47. Mortensen PB, Clausen MR (1996) Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease. Scand J Gastroenterol Suppl 216:132–148CrossRefGoogle Scholar
  48. Nakatsu Y, Seno Y, Kushiyama A, Sakoda H, Fujishiro M, Katasako A, Mori K, Matsunaga Y, Fukushima T, Kanaoka R, Yamamotoya T, Kamata H, Asano T (2015) The xanthine oxidase inhibitor febuxostat suppresses development of non alcoholic steatohepatitis in a rodent model. Am J Physiol Gastrointest Liver Physiol 309:G42–G51CrossRefGoogle Scholar
  49. Noaguchi H, Tazawa Y, Nishinomiya F, Takada G (1995) The relationship between serum transaminases activities and fatty liver in children with simple obesity. Acta Paediatr Jpn 37:621–625CrossRefGoogle Scholar
  50. Ohyama T, Sato K, Yamazaki Y, Hashizume H, Horiguchi N, Kakizaki S, Mori M, Kusano M, Yamada M (2014) MK-0626, a selective DPP-4 inhibitor, attenuates hepatic steatosis in ob/ob mice. World J Gastroenterol 20:16227–16235CrossRefGoogle Scholar
  51. Olatunji LA, Michael OS, Adewumi FO, Aiyegboyin IJ, Olatunji VA (2012) Combined estrogen-progestogen but not progestogen-only oral contraceptive alters glucose tolerance and plasma lipid profile in female rats. Pathophysiology 19:29–34CrossRefGoogle Scholar
  52. Olatunji LA, Omolekulo TE, Usman TO, Kim I (2016) Improvement of oral contraceptive-induced glucose dysregulation and dyslipidemia by valproic acid is independent of circulating corticosterone. Arch Physiol Biochem 122:123–129CrossRefGoogle Scholar
  53. Olatunji LA, Michael OS, Adeyanju OA, Areola ED, Soladoye AO (2017) Anti-inflammatory and antithrombotic effects of nicotine exposure in oral contraceptive-induced insulin resistance are glucocorticoid-independent. Pharmacol Rep 69:512–519CrossRefGoogle Scholar
  54. Peng Z, Borea P, Wilder T, Yee H, Chiriboga L, Blackburn M et al (2009) Adenosine signaling contributes to ethanol-induced fatty liver in mice. J Clin Invest 119(3):582–594CrossRefGoogle Scholar
  55. Priyadarshini M, Thomas A, Reisetter AC, Scholtens DM, Wolever TM, Josefson JL et al (2014) Maternal short chain fatty acids are associated with metabolic parameters in mothers and newborns. Transl Res 164(2):153–157CrossRefGoogle Scholar
  56. Rector RS, Thyfault JP, Wei Y, Ibdah JA (2008) Non-alcoholic fatty liver disease and the metabolic syndrome: an update. World J Gastroenterol 14:185–192CrossRefGoogle Scholar
  57. Roepke TA (2009) Oestrogen modulates hypothalamic control of energy homeostasis through multiple mechanisms. J Neuroendocrinol 21:141–150CrossRefGoogle Scholar
  58. Schulze PC (2009) Myocardial lipid accumulation and lipotoxicity in heart failure. J Lipid Res 50:2137–2138CrossRefGoogle Scholar
  59. Sell H, Bluher M, Kloting N, Schlich R, Willems M, Ruppe F, Knoefel WT, Dietrich A, Fielding BA, Arner P, Frayn KN, Eckel J (2013) Adipose dipeptidyl peptidase-4 and obesity: correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro. Diabetes Care 36:4083–4090CrossRefGoogle Scholar
  60. Sertoglu E, Ercin CN, Celebi G, Gurel H, Kayadibi H, Genc H, Kara M, Dogru T (2014) The relationship of serum uric acid with non-alcoholic fatty liver disease. Clin Biochem 47:383–388CrossRefGoogle Scholar
  61. Shaw JE, Sicree RA, Zimmet PZ (2010) Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87:4–14CrossRefGoogle Scholar
  62. Shinoda M, Latour MG, Lavoie JM (2002) Effects of physical training on body composition and organ weights in ovariectomized and hyperestrogenic rats. Int J Obes Relat Metab Disord 26:335–343CrossRefGoogle Scholar
  63. Siler SQ, Neese RA, Hellerstein MK (1999) De novo lipogenesis, lipid kinetics, and whole-body lipid balance in humans after acute alcohol consumption. Am J Clin Nutr 70:928–936CrossRefGoogle Scholar
  64. Soha SE, Khaled A, Amani AE (2014) Comparing the effects of inorganic nitrate and allopurinol in renovascular complications of metabolic syndrome in rats: role of nitric oxide and uric acid complications of metabolic syndrome role of nitric oxide and uric acid. Arch Med Sci 10:537–545Google Scholar
  65. Tirosh A, Shai I, Tekes-Manova D, Israeli E, Pereg D, Shochat T, Kochba I, Rudich A, Israeli Diabetes Research Group (2005) Normal fasting plasma glucose levels and type 2 diabetes in young men. N Engl J Med 353:1454–1462CrossRefGoogle Scholar
  66. Tirosh A, Shai I, Bitzur R, Kochba I, Tekes-Manova D, Israeli E, Shochat T, Rudich A (2008) Changes in triglyceride levels over time and risk of type 2 diabetes in young men. Diabetes Care 31:2032–2037CrossRefGoogle Scholar
  67. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM (2012) Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61(2):364–371CrossRefGoogle Scholar
  68. Utzschneider KM, Kahn SE (2006) The role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab 91(12):4753–4761CrossRefGoogle Scholar
  69. Vernon G, Baranova A, Younossi ZM (2011) Systematic review: the epidemiology and natural history of nonalcoholic fatty liver disease and non alcoholic steatohepatitis in adults. Ailment Pharmacol Ther 34:274–285CrossRefGoogle Scholar
  70. Vinolo MA, Rodrigues HG, Nachbar RT, Curi R (2011) Regulation of inflammation by short chain fatty acids. Nutrients 3:858–876CrossRefGoogle Scholar
  71. Vrieze A, Van Nood E, Holleman F, Salojärvi J, Kootte RS, Bartelsman JFWM et al (2012) Transfer of intestinal microbiotafrom lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterol 143:913–916CrossRefGoogle Scholar
  72. Williams KH, Vieira De Ribeiro AJ, Prakoso E, Veillard AS, Shackel NA, Brooks B et al (2015) Circulating dipeptidyl peptidase-4 activity correlates with measures of hepatocyte apoptosis and fibrosis in non-alcoholic fatty liver disease in type 2 diabetes mellitus and obesity: a dual cohort cross-sectional study. J Diabetes 7(6):809–819CrossRefGoogle Scholar
  73. Wilson PW, Meigs JB, Sullivan L, Fox CS, Nathan DM, D’Agostino RB Sr (2007) Prediction of incident diabetes mellitus in middle-aged adults: the Framingham Offspring Study. Arch Intern Med 167:1068–1074CrossRefGoogle Scholar
  74. Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ (2006) Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 40:235–243CrossRefGoogle Scholar
  75. Yamashita H, Fujisawa K, Ito E, Idei S, Kawaguchi N, Kimoto M et al (2007) Improvement of obesity and glucose tolerance by acetate in Type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Biosci Biotechnol Biochem 71(5):1236–1243CrossRefGoogle Scholar
  76. Yamashita H, Maruta H, Jozuka M, Kimura R, Iwabuchi H, Yamato M et al (2009) Effects of acetate on lipid metabolism in muscles and adipose tissues of type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Biosci Biotechnol Biochem 73(3):570–576CrossRefGoogle Scholar
  77. Yang D, Zhang Y, Nguyen HG, Koupenova M, Chauhan AK, Makitalo M, Jones MR, St Hilaire C, Seldin DC, Toselli P, Lamperti E, Schreiber BM, Gavras H, Wagner DD, Ravid K (2006) The A2B adenosine receptor protects against inflammation and excessive vascular adhesion. J Clin Invest 116:1913–1923CrossRefGoogle Scholar
  78. Zhang S, Du T, Zhang J, Lu H, Lin X, Xie J et al (2017) The triglyceride and glucose index (TyG) is an effective biomarker to identify nonalcoholic fatty liver disease. Lipids Health Dis 16:1CrossRefGoogle Scholar
  79. Zhong J, Rao X, Rajagopalan S (2013) An emerging role of dipeptidyl peptidase 4 (DPP4) beyond glucose control: potential implications in cardiovascular disease. Atherosclerosis 226:305–314CrossRefGoogle Scholar
  80. Zhong J, Maiseyeu A, Davis SN, Rajagopalan S (2015) DPP4 in cardiometabolic disease recent insights from the laboratory and clinical trials of DPP4 inhibition. Circ Res 116:1491–1504sCrossRefGoogle Scholar
  81. Zillessen P, Celner J, Kretschmann A, Pfeifer A, Racké K, Mayer P (2016) Metabolic role of dipeptidyl peptidase 4 (DPP4) in primary human (pre) adipocytes. Sci Rep 6:23074CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Tolulope Eniola Omolekulo
    • 1
  • Olugbenga Samuel Michael
    • 1
    • 2
  • Lawrence Aderemi Olatunji
    • 1
    Email author
  1. 1.HOPE Cardiometabolic Research Team & Department of Physiology, College of Health SciencesUniversity of IlorinIlorinNigeria
  2. 2.Department of Physiology, Bowen University IwoIwoNigeria

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