ASPROSIN: A NOVEL BIOMARKER OF TYPE 2 DIABETES MELLITUS

Asmaa Elnagar, Hussein I. El-Belbasi, Ibrahim F. Rehan, Khalifa El-Dawy

Abstract


Type 2 diabetes mellitus has a deadly toll on human health. Therefore, more attention needs to be paid for the creation of biomarker to indicate the newly diagnostic type 2 diabetes and effective therapy. It well known that adipose tissue of mammals can store energy and secrete such hormones. Therefore, obesity is associated with hyperinsulinemia and insulin resistance. Recently, newly identified glucogenic hormone named “asprosin” has been developed in white adipose tissue, encoded by the gene Fibrillin 1 (Fbn1). Fbn1 is a 230-kb gene with 65 coding exons. These exons encode a 2,871-amino-acid long proprotein called proFibrillin which is proteolytically cleaved near its C-terminus by the enzyme furin convertase to give Fbn1, a member of the fibrillin family, in addition the 140-amino-acid long protein hormone asprosin. It has a metabolic role during fasting condition as it induces liver to secrete glucose for maintaining homeostasis as well as centrally stimulates appetite. It was reported that plasma asprosin concentrations increased in human/mice with type 2 diabetes compared with controls. However, it was significantly reduced in patients with neonatal progeriod syndrome who had characteristic features of low appetite and extreme leanness. This syndrome is due to the truncated mutation in Fbn1. Although the great biological role of asprosin in vivo, it still limited in research, particularly in the therapy of type 2 diabetes. This study aimed to provide an overview of asprosin and its possibility to be used as a novel biomarker of type 2 diabetes and obesity.

Key words: Asprosin; type 2 diabetes mellitus; Fbn1 gene


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Ogurtsova K, da Rocha Fernandes, JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, Cavan D, Shaw JE, Makaroff LE. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128: 40–50.

Andrade-Oliveira V, Câmara NO, Moraes-Vieira PM. Adipokines as drug targets in diabetes and underlying disturbances. J Diabetes Res 2015;2015: 681612.

Ahima RS. Adipose tissue as an endocrine organ. Obesity 2006;14 (S8): 242–9.

Booth A, Magnuson A, Fouts J, Foster M. Adipose tissue: an endocrine organ playing a role in metabolic regulation. Horm Mol Biol Clin Investig 2016; 26 (1): 25–42.

Czech MP. Insulin action and resistance in obesity and type 2 diabetes. Nat Med 2017;23 (7): 804–14.

Clark M, Hoenig M. Metabolic effects of obesity and its interaction with endocrine diseases. Vet Clin North Am Small Anim Pract2016;46 (5): 797–815.

Zhang L, Fu Y, Zhou N, Cheng X, Chen C. Circulating neuregulin 4 concentrations in patients with newly diagnosed type 2 diabetes: a cross-sectional study. Endocrine 2017; 57 (3): 535–8.

Sun L, Qi Q, Zong G, Ye X, Li H, Liu X, Zheng H, Hu F.B, Liu Y, Lin X. Elevated plasma retinol-binding protein 4 is associated with increased risk of type 2 diabetes in middle-aged and elderly Chinese adults–3. J Nutr 2014;144 (5): 722–8.

Conte C, Fabbrini E, Kars M, Mittendorfer B, Patterson BW, Klein S. Multiorgan insulin sensitivity in lean and obese subjects. Diabetes Care 2012; 35 (6): 1316–21.

Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW, Neifing JL, Ward WK, Beard JC, Palmer JP. Quantification of the relationship between insulin sensitivity and β-cell function in human subjects: evidence for a hyperbolic function. Diabetes 1993; 42 (11): 1663–72.

Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, Saha PK, Del Solar M, Zhu B, York B, Sarkar P, Rendon DA, Gaber MW, LeMaire SA, Coselli JS, Milewicz DM, Sutton VR, Butte NF, Moore DD, Chopra AR. Asprosin, a fasting-induced glucogenic protein hormone. Cell 2016; 165 (3): 566–79.

Tokumoto S, Okamura E, Abe M, Honjo S, Hamasaki A. Inverse association between fasting insulin levels and postprandial changes of plasma asprosin concentration in patients with type 2 diabetes. Diabetologia 2017; (60): 270.

Schumann U, Qiu S, Enders K, Bosnyák E, Laszlo R, Machus K, Trájer E, Jaganathan S, Zügel M, Steinacker JM. Asprosin, A newly identified fasting-induced hormone is not elevated in obesity and is insensitive to acute exercise.Med Sci Sports Exerc 2017;49 (5): 1023.

Wang Y, Qu H, Xiong X, Qiu Y, Liao Y, Chen Y, Zheng Y, Zheng H. Plasma asprosin concentrations are increased in individuals with glucose dysregulation and correlated with insulin resistance and first-phase insulin secretion. Mediators of Inflamm 2018; 2018: 9471583. doi: 10.1155/2018/9471583.

Zhang L, Chen C, Zhou N, Fu Y, Cheng X. Circulating asprosin concentrations are increased in type 2 diabetes mellitus and independently asso-ciated with fasting glucose and triacylglycerol . Clin Chimica Acta 2017.

Duerrschmid C, He Y, Wang C, Li C, Bournat JC, Romere C, Saha PK, Lee ME, Phillips KJ, Jain M, Jia P. Asprosin is a centrally acting orexigenic. Nat Med 2017;23 (12): 1444.

Davis MR, Arner E, Duffy CR, De Sousa PA, Dahlman I, Arner P, Summers KM. Datasets of genes coexpressed with Fbn1 in mouse adipose tissue and during human adipogenesis. Data Brief 2016; 8: 851-857.

Kajimura S. Adipose tissue in 2016: Advances in the understanding of adipose tissue biology. Nat Rev Endocrinol 2017;13 (2): 69–70.

Lönnqvist L, Reinhardt D, Sakai L, Peltonen L. Evidence for furin-type activity-mediated C-terminal processing of proFibrillin-1 and interference in the processing by certain mutations. Hum Mol Genet 1998;7 (13): 2039–44.

Sinha G. Leptin therapy gains FDA approval. Nat Biotechnol 2014;32 (4): 300–2.

Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerbäck S, Nuutila P. Functional brown adipose tissue in healthy adults. N Engl J Med 2009; 360 (15): 1518–25.

Villarroya F, Cereijo R, Villarroya J, Giralt M. Brown adipose tissue as a secretory organ. Nat Rev Endocrinol 2016;13 (1): 26–35.

Shinoda K, Luijten IH, Hasegawa Y, Hong H, Sonne SB, Kim M, Xue R, Chondronikola M, Cypess AM, Tseng YH, Nedergaard J. Genetic and functional characterization of clonally derived adult human brown adipocytes. Nat Med 2015;21 (4): 389–94.

Kajimura S, Spiegelman BM, Seale P. Brown and beige fat: physiological roles beyond heat generation. Cell Metab 2015;22 (4): 546–59.

Min SY, Kady J, Nam M, Rojas-Rodriguez R, Berkenwald A, Kim JH, Noh HL, Kim JK, Cooper MP, Fitzgibbons T, Brehm MA. Human'

brite/beige'adipocytes develop from capillary netw-orks, and their implantation improves metabolic homeostasis in mice. Nat Med 2016;22 (3): 312–8.

Milewicz DM, Grossfield J, Cao SN, Kielty C, Covitz W, Jewett T. A mutation in Fbn1 disrupts proFibrillin processing and results in isolated skeletal features of the Marfan syndrome. J Clin Invest 1995; 95 (5): 2373–8.

Birrell MA, Maher SA, Dekkak B, Jones V, Wong S, Brook P, Belvisi MG. Anti-inflammatory effects of PGE2 in the lung: role of the EP4 receptor subtype. Thorax 2015; 70 (8): 740–7.

Julliard A, Al Koborssy D, Fadool DA, Palouzier-Paulignan B. Nutrient sensing: another chemosensitivity of the olfactory system. Front Physiol 2017;8: 468.

Aronoff SL, Berkowitz K, Shreiner B, Want L. Glucose metabolism and regulation: beyond insulin and 2004. Diabetes Spectr 2004; 17 (3): 183–90.

Sauvanet JP. Congress of the international diabetes federation (IDF-Paris 2003). Press Med 2003;32 (39): 1864–8.

Garvey WT, Garber AJ, Mechanick JI, Bray GA, Dagogo-Jack S, Einhorn D, Grunberger G, Handelsman Y, Hennekens CH, Hurley DL, McGill J. The Aace Obesity Scientific, American association of clinical endocrinologists and American college of endocrinology position statement on the advanced framework for a new diagnosis of obesity as a chronic disease. Endocr Pract 2014;20 (9): 977–89.

O'neill S, O'driscoll L. Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obesity Rev 2015;16 (1): 1–12.

Hotamisligil GS. Inflammation and metabolic disorders. Nat 2006;444 (7121): 860–7.

Jenei-Lanzl Z, Zwingenberg J, Lowin T, Anders S, Straub RH. Proinflammatory receptor switch from Gαs to Gαi signaling by β-arrestin-mediated PDE4 recruitment in mixed RA synovial cells. Brain Behav Immun 2015;50: 266–74.

Jiang J, Dingledine R. Prostaglandin receptor EP2 in the crosshairs of anti-inflammation, anti-cancer, and neuroprotection. Trends Pharmacol Sci 2013; 34 (7): 413–23.

Zimmerman NP, Kumar SN, Turner JR, Dwinell MB. Cyclic AMP dysregulates intestinal epithelial cell restitution through PKA and RhoA. Inflamm Bowel Dis.2012; 18 (6): 1081–91.

Ju X, Ijaz T, Sun H, LeJeune W, Vargas G, Shilagard T, Recinos III A, Milewicz DM, Brasier AR, Tilton RG. IL-6 regulates extracellular matrix remodeling associated with aortic dilation in a Fibrillin-1 hypomorphic mgR/mgR mouse model of severe Marfan syndrome. J Am Heart Assoc 2014;3 (1): e000476.

Andersson DP, Laurencikiene J, Acosta JR, Ryden M, Arner P. Circulating and adipose levels of adipokines ssociated with insulin sensitivity in nonobese subjects with type 2 diabetes. J Clin Endocrinol Metab 2016;101 (10): 3765–71.

Kovacs D, Lovaszi M, Poliska S, Olah A, Biro T, Veres I, Zouboulis CC, Stahle M, Ruhl R, Remenyik E, Torocsik D. Sebocytes differentially express and secrete adipokines. Exp Dermatol 2016;25 (3): 194–9.

Titchenell PM, Lazar MA, Birnbaum MJ. Unraveling the regulation of hepatic metabolism by insulin. Trends Endocrinol Metab 107; 28 (7): 497–505.

Wu L, Parhofer KG. Diabetic dyslipidemia. Metab 2014;63 (12): 1469–79.

Combs TP, Berg AH, Rajala MW, Klebanov S, Iyengar P, Jimenez-Chillaron JC, Patti ME, Klein SL, Weinstein RS, Scherer PE. Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin. Diabetes 2003;52 (2): 268–76.

Saad MF, Damani S, Gingerich RL, Riad-Gabriel MG, Khan A, Boyadjian R, Jinagouda SD, el-Tawil K, Rude RK, Kamdar V. Sexual dimorphism in plasma leptin concentration. J Clin Endocrinol Metab 1997; 82 (2): 579–84.

O'Neill B, Simha V, Kotha V, Garg A. Body fat distribution and metabolic variables in patients with neonatal progeroid syndrome. Am J Med Genet A 2007;143A (13): 1421–30.

Pereira L, Lee SY, Gayraud B, Andrikopoulos K, Shapiro SD, Bunton T, Biery NJ, Dietz HC, Sakai LY, Ramirez F. Pathogenetic sequence for aneurysm revealed in mice underexpressing Fibrillin-1. Proc Natl Acad Sci USA 1999; 96 (7): 3819––3.

Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S. A role for ghrelin in the central regulation of feeding. Nat 2001;409 (6817): 194–8.

Del Prato S, Tiengo A. The importance of first-phase insulin secretion: implications for the therapy of type 2 diabetes mellitus. Diabetes metab Res Rev 2001;17 (3): 164–74.

Bunt JC, Krakoff J, Ortega E, Knowler WC, Bogardus C. Acute insulin response is an independent predictor of type 2 diabetes mellitus in individuals with both normal fasting and 2‐h plasma glucose concentrations. Diabetes Metabolism Res Rev 2007;23 (4): 304–10.

Dunmore SJ, Brown JE. The role of adipokines in beta-cell failure of type 2 diabe-tes. J Endocrinol 2013; 216 (1): 37–45.


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