Betatrophin is correlated with glucagon and insulin release rather than insulin resistance marker in type 2 diabetes mellitus Iraqi women


  • Athir K. Mohammed Department of Biology, College of Sciences, University of Baghdad, AL-Jaderyia Campus, Baghdad
  • Faris A. K. Khazaal Obesity Research and Therapy Unit, Alkindy College of Medicine, University of Baghdad



Betatrophin, Glucagon, Type 2 diabetes, HOMA-β, Homeostasis model assessment insulin resistance (HOMA-‎IR), Uric acid


Background: Betatrophin mainly expressed in liver and adipose tissue, stimulates pancreatic β-cell proliferation in insulin resistance state and improves metabolic process‎ regulation. This study aimed to understand effective roles of betatrophin in diabetic and non-diabetic Iraqi women. Also, it’s correlation with some insulin markers, metabolic parameters and glucagon.

Methods: Eighty women participated in this cross-sectional study, (mean body mass index: 21 - 49 kg/m2; mean age: 25-50 years) were enrolled and classified according to the presence of diabetes into 2 groups (40 diabetic and 40 non-diabetic). Anthropometric, biochemical and metabolic parameters measured.

Results: Betatrophin level had no statistically significant differences between non-diabetics and diabetics. Serum betatrophin levels had no statistically significant positive or negative correlations with age, anthropometric, lipid profile, diabetic parameters, thyroid stimulating hormone, glucagon, irisin, glucagon like peptide -1 and hepatocyte growth factor except uric acid (r=0.2539, P =0.0231). Serum betatrophin had no statistically significant correlations with all variables in non-diabetic and diabetic groups except with homoeostasis model assessment- for β-cell function (HOMA-β) and glucagon (r=0.3647, P=0.0207; r=0.3403, P=0.0317 respectively) in the diabetic group. Stepwise regression showed that only uric acid was independently related factors to circulating betatrophin β=‎0.8500, P=0.02.

Conclusions: Betatrophin was positively correlated with HOMA-β and glucagon in type 2 diabetes mellitus women. Uric acid was a direct independent predictor of betatrophin level.


Lickert H. Betatrophin fuels β cell proliferation: first step toward regenerative therapy? Cell Metab. 2013;18(1):5-6.

Crunkhorn S. Metabolic disorders: betatrophin boosts β-cells. Nat Rev Drug Discov. 2013;12(7):504.

Yi P, Park JS, Melton DA. Betatrophin. A hormone that controls pancreatic beta cell proliferation. Cell. 2013;153(4):747-58.

Zhang R. Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels. Biochem Biophys Res Commun. 2012;424(4):786-92.

Ren G, Kim JY, Smas CM. Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism. Am J Physiol Metab. 2012;303(3):334-51.

Dong XY, Pang XW, Yu ST, Su YR, Wang HC, Yin YH, et al. Identification of genes differentially expressed in human hepatocellular carcinoma by a modified suppression subtractive hybridization method. Int J cancer. 2004;112(2):239-48.

Quagliarini F, Wang Y, Kozlitina J, Grishin N V, Hyde R, Boerwinkle E, et al. Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci U S A. 2012;109(48):19751-6.

Bostrom P, Wu J, Jedrychowski MPM, Korde A, Ye L, Lo JC, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463-8.

Sanchis GF, Perez QC. The p38-PGC-1α–irisin–betatrophin axis. Adipocyte. 2014;3(1):67-8.

Lohman TG, Roche AF, Martorell R, Pelletiet D. Anthropometric standardization reference manual. Lohman TG, Roche AF, Martorell R, editors. Am J Hum Biol. 1992;4(3):425-6.

Frisancho AR. Anthropometric standards for the assessment of growth and nutritional status. A.R. The University of Michigan Press. 1990:189.

Douketis JB, Paradis G, Keller H, Martineau C. Canadian guidelines for body weight classification in adults: application in clinical practice to screen for overweight and obesity and to assess disease risk. Canadian Med Asso J. 2005;172(8):995-8.

Flier JS, Flier ME. Obesity. In: DL K, editor. Harrisons’s principles of Internal Medicine‎. 16th editi. USA, McGraw-Hill Companies‎; 2005:422-30.

World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: Report of a WHO/IDF consultation. Production. 2006;1-52.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9.

Guo K, Lu J, Yu H, Zhao F, Pan P, Zhang L. Serum betatrophin concentrations are significantly increased in overweight but not in obese or type 2 diabetic individuals. Obesity. 2015;23(4):793-7.

Xie X, Gao T, Yang M, Chen P, Jin H, Yang L, et al. Associations of betatrophin levels with irisin in Chinese women with normal glucose tolerance. Diabetol Metab Syndr. 2015;7:26.

Fu Z, Berhane F, Fite A, Seyoum B, Abou-Samra AB, Zhang R. Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity. Sci Rep. 2014;4:5013.

Yamada H, Saito T, Aoki A, Asano T. Circulating betatrophin is elevated in patients with type 1 and type 2 diabetes. Endocr J. 2015;62(5):417-21.

Ambrosi GJ, Pascual E, Catalan V, Rodriguez A, Ramirez B, Silva C, et al. Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes. J Clin Endocrinol Metab. 2014;99(10):2004-9.

Tokumoto S, Hamamoto Y, Fujimoto K, Yamaguchi E, Okamura E, Honjo S, et al. Correlation of circulating betatrophin concentrations with insulin secretion capacity, evaluated by glucagon stimulation tests. Diabet Med. 2015;32(5):653-6.

Yi M, Chen R, Yang R, Guo X. Betatrophin acts as a diagnostic biomarker in type 2 diabetes mellitus and is negatively associated with hdl-cholesterol. Int J Endocrinol. 2015;47:9157.

Espes D, Martinell M, Carlsson PO. Increased circulating betatrophin concentrations in patients with type 2 diabetes. Int J Endocrinol. 2014;6.

Ebert T, Kralisch S, Wurst U, Lossner U, Kratzsch J, Blüher M, et al. Betatrophin levels are increased in women with gestational diabetes mellitus compared to healthy pregnant controls. Eur J Endocrinol. 2015;173(1):1-7.

Farha AM, Abubaker J, Khairi AI, Cherian P, Noronha F, Hu FB, et al. Higher plasma betatrophin/ANGPTL8 level in type 2 diabetes subjects does not correlate with blood glucose or insulin resistance. Sci Rep. 2015;5:1-8.

Wang L, Song J, Wang C, Lin P, Liang K, Sun Y, et al. Circulating levels of betatrophin and irisin are not associated with pancreatic β -cell function in previously diagnosed type 2 diabetes mellitus patients. J Diabetes Res. 2016;2016:1-8.

Hu H, Sun W, Yu S, Hong X, Qian W, Tang B, et al. Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients. 2014;37(10):2718-22.

Catalan V, Ambrosi GJ, Rodriguez A, Silva C, Rotellar F, Gil MJ, et al. Expression of caveolin-1 in human adipose tissue is up regulated in obesity and obesity-associated type 2 diabetes mellitus and related to inflammation. Clin Endocrinol. 2008;68(2):213-9.

Calan M, Dokuzlar O, Aygun K, Yesil P, Arkan T, Kocaer MAO, et al. SUN-1009:Relationship between circulating betatrophin levels and insulin resistance in prediabetic subjects.’ Endo meetings. 2014:21-4.

Portois L, Tastenoy M, Viollet B, Svoboda M. Functional analysis of the glucose response element of the rat glucagon receptor gene in insulin-producing INS-1 cells. Biochim Biophys Acta - Gene Struct Expr. 2002;1574(2):175-86.

Muller WA, Faloona GR, Unger RH. The effect of experimental insulin deficiency on glucagon secretion. J Clin Invest. 1971;50(9):1992-9.

Omar B, Winzell SM, Ahren B. Conditional glucagon receptor overexpression has multi-faceted consequences for beta-cell function. Metabolism. 2014;63(12):1568-76.

Kimball SR, Siegfried BA, Jefferson LS. Glucagon represses signaling through the mammalian target of rapamycin in rat liver by activating AMP-activated protein kinase. J Biol Chem. 2004;279(52):54103-9.

Cao W, Collins QF, Becker TC, Robidoux J, Lupo EG, Xiong Y, et al. P38 Mitogen-activated protein kinase plays a stimulatory role in hepatic gluconeogenesis. J Biol Chem. 2005;280(52):42731-7.

Chen J, Ishac EJ, Dent P, Kunos G, Gao B. Effects of ethanol on mitogen-activated protein kinase and stress-activated protein kinase cascades in normal and regenerating liver. Biochem J. 1998;334(3):669-76.

Puigserver P. Tissue-specific regulation of metabolic pathways through the transcriptional coactivator PGC1-alpha. Int J Obes. 2005;29(1):5-9.

Corrales PE, Ambrosi GJ, Moncada R, Valenti V, Catalan V, Rodriguez A, et al. Circulating ANGPTL8/ betatrophin concentrations are increased after surgically induced weight loss, but not after diet-induced weight loss. Obes Surg. 2016;1-9.

Tang S, Zhang R, Jiang F, Wang J, Chen M, Peng D, et al. Circulating irisin levels are associated with lipid and uric acid metabolism in a Chinese population. Clin Exp Pharmacol Physiol. 2015;42(9):896-901.

Fernández BS, Folgueira C, Seoane LM, Casanueva FF, Dieguez C, Castelao C, et al. Circulating betatrophin levels are increased in anorexia and decreased in morbidly obese women. J Clin Endocrinol Metab. 2015;100(9):1188-96.

Erol O, Ellidag HY, Ayık H, Ozel MK, Derbent AU, Yılmaz N. Evaluation of circulating betatrophin levels in gestational diabetes mellitus. Gynecol Endocrinol. 2015;31(8):652-6.




How to Cite

Mohammed, A. K., & Khazaal, F. A. K. (2016). Betatrophin is correlated with glucagon and insulin release rather than insulin resistance marker in type 2 diabetes mellitus Iraqi women. International Journal of Research in Medical Sciences, 4(10), 4264–4271.



Original Research Articles