Adipokines and their role in acute pancreatitis:

Saira  Rafaqat; Irena Radoman Vujacic; Dimitrios Patoulias; Huma Khurshid; Aleksandra Klisic

doi:10.5937/jomb0-47515

Saira Rafaqat
Irena Radoman Vujacic Clinical Center of Montenegro, Department of Internal Medicine, University of Montenegro-Faculty of Medicine, Podgorica, Montenegro
Dimitrios Patoulias
Huma Khurshid
Aleksandra Klisic

DOI: https://doi.org/10.5937/jomb0-47515

Sažetak

Akutni pankreatitis (AP) se karakteriše inflamatornim odgovorom koji vodi edemu i hemoragiji tkiva pankreasa. U težim stanjima može voditi i nekrozi pankreasa. Adipokini su biološki aktivni molekuli koje sekretuje masno tkivo, a koji imaju širok spektar dejstva. Adipokini i citokini nisu samo produkt belog masnog tkiva, već i masnog tkiva koje okružuje pankreas, igrajući važnu ulogu u inflamatornom odgovoru organizma. Prisustvo uvećanog masnog tkiva, često povezano sa gojaznošću, dovodi se u vezu sa pojačanim inflamatornim odgovorom u slučajevima AP. Podaci iz literature ukazuju na veliki broj otkrivenih adipokina. Ovaj revijski članak predstavlja prikaz uloge pojedinih adipokina u AP. Adipokini mogu biti obećavajući dijagnostički i terapijski biomarkeri u AP. Ipak, potrebna su dublja saznanja o signalnim putevima adipokina i potencijalnoj terapijskoj ulozi ovih biomarkera u AP.

Reference

Shu W, Wan J, Chen J, He W, Zhu Y, Lu N, Xia L. Elevated arterial lactate level as an independent risk factor for pancreatic infection in moderately severe acute pancreatitis. Pancreatology 2019; 19: 653-7.

Portelli M, Jones CD. Severe acute pancreatitis: pathogenesis, diagnosis and surgical management. Hepatobiliary Pancreat Dis Int 2017; 16: 155-9.

Lee AHH, Lee WS, Anderson D. Severe pancreatitis complicated by abdominal compartment syndrome managed with decompressive laparotomy: a case report. BMC Surg 2019; 19: 113.

Li H, Yan K. Comparison of death risk predictions of 192 patients with severe acute pancreatitis by acute physiological function and chronic health status scoring system II and IV. Chin J Digestol 2016; 36: 177-81.

Fasshauer M, Blüher M. Adipokines in health and disease. Trends Pharmacol Sci 2015; 36(7): 461-70.

Lau WB, Ohashi K, Wang Y, Ogawa H, Murohara T, Ma XL, Ouchi N. Role of adipokines in cardiovascular disease. Circulation Journal 2017; 81(7): 920-8.

Premkumar R, Phillips AR, Petrov MS, Windsor JA. The clinical relevance of obesity in acute pancreatitis: targeted systematic reviews. Pancreatology 2015; 15(1): 25–33.

Noel P, Patel K, Durgampudi C, Trivedi RN, de Oliveira C, Crowell MD, Pannala R, Lee K, Brand R, Chennat J, Slivka A, Papachristou GI, Khalid A, Whitcomb DC, DeLany JP, Cline RA, Acharya C, Jaligama D, Murad FM, Yadav D, Navina S, Singh VP. Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections. Gut 2016; 65(1): 100–11.

Meyrignac O, Lagarde S, Bournet B, Mokrane FZ, Buscail L, Rousseau H, Otal P. Acute pancreatitis: extrapancreatic necrosis volume as early predictor of severity. Radiology 2015; 276(1): 119–28.

Karpavicius A, Dambrauskas Z, Gradauskas A, Samuilis A, Zviniene K, Kupcinskas J, Brimas G, Meckovski A, Sileikis A, Strupas K. The clinical value of adipokines in predicting the severity and outcome of acute pancreatitis. BMC Gastroenterol 2016; 16(1): 99.

Sharma A, Muddana V, Lamb J, Greer J, Papachristou GI, Whitcomb DC. Low serum adiponectin levels are associated with systemic organ failure in acute pancreatitis. Pancreas 2009; 38: 907–12.

Schäffler A, Landfried K, Völk M, Fürst A, Büchler C, Schölmerich J, Herfarth H. Potential of adipocytokines in predicting peripancreatic necrosis and severity in acute pancreatitis: pilot study. J Gastroenterol Hepatol 2007; 22: 326–34.

Schäffler A, Hamer O, Dickopf J, Goetz A, Landfried K, Voelk M, Herfarth H, Kopp A, Büchler C, Schölmerich J, Brünnler T. Admission resistin levels predict peripancreatic necrosis and clinical severity in acute pancreatitis. Am J Gastroenterol 2010; 105: 2474–84.

Schäffler A, Hamer OW, Dickopf J, Goetz A, Landfried K, Voelk M, Herfarth H, Kopp A, Buechler C, Schölmerich J, Brünnler T. Admission visfatin levels predict pancreatic and peripancreatic necrosis in acute pancreatitis and correlate with clinical severity. Am J Gastroenterol 2011; 106: 957–67.

Türkoğlu A, Böyük A, Tanrıverdi MH, Gündüz E, Dusak A, Kaplan İ, Gümüş M. The potential role of BMI, plasma leptin, nesfatin-1 and ghrelin levels in the early detection of pancreatic necrosis and severe acute pancreatitis: a prospective cohort study. Int J Surg 2014; 12(12): 1310–3.

Panek J, Bonior J, Pieton J, Jaworek J. Serum leptin and ghrelin levels in patients in the early stages of acute biliary pancreatitis and different degrees of severity. Pol Przegl Chir 2014; 86(5): 211–7.

Yu X, Zhang N, Wu J, Zhao Y, Liu C, Liu G. Predictive value of adipokines for the severity of acute pancreatitis: a meta-analysis. https://doi.org/10.21203/rs.3.rs-2769468/v1

Karpavicius A, Dambrauskas Z, Sileikis A, Vitkus D, Strupas K. Value of adipokines in predicting the severity of acute pancreatitis: comprehensive review. World J Gastroenterol 2012; 18(45): 6620-7.

Wos-Wroniewicz E, Caban M, Malecka-Panas E. Role of adipokines in the assessment of severity and predicting the clinical course of acute pancreatitis. J Physiol Pharmacol 2020; 71(5). doi: 10.26402/jpp.2020.5.01.

Kadomatsu T, Endo M, Miyata K, Oike Y. Diverse roles of ANGPTL2 in physiology and pathophysiology. Trends Endocrinol Metab 2014; 25: 245–54.

Tabata M, Kadomatsu T, Fukuhara S, Miyata K, Ito Y, Endo M, Urano T, Zhu HJ, Tsukano H, Tazume H, Kaikita K, Miyashita K, Iwawaki T, Shimabukuro M, Sakaguchi K, Ito T, Nakagata N, Yamada T, Katagiri H, Kasuga M, Ando Y, Ogawa H, Mochizuki N, Itoh H, Suda T, Oike Y. Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance. Cell Metab 2009; 10: 178–88.

Whitcomb DC, Muddana V, Langmead CJ, Houghton FD Jr, Guenther A, Eagon PK, Mayerle J, Aghdassi AA, Weiss FU, Evans A, Lamb J, Clermont G, Lerch MM, Papachristou GI. Angiopoietin-2, a regulator of vascular permeability in inflammation, is associated with persistent organ failure in patients with acute pancreatitis from the United States and Germany. Am J Gastroenterol 2010; 105: 2287–92.

Sporek M, Dumnicka P, Gala-Bladzinska A, Ceranowicz P, Warzecha Z, Dembinski A, Stepien E, Walocha J, Drozdz R, Kuzniewski M, Kusnierz-Cabala B. Angiopoietin-2 is an early indicator of acute pancreatic-renal. Mediators Inflamm 2016; 2016: 5780903.

Lv Y, Yao Y, Liu Q, Lei J. Accuracy of angiopoietin-2 for predicting organ failure in patients with acute pancreatitis: a systematic review and meta-analysis. J Int Med Res 2021; 49(2): 300060520986708.

Jaworek J, Szklarczyk J, Kot M, Góralska M, Jaworek A, Bonior J, Leja-Szpak A, Nawrot-Porąbka K, Link-Lenczowski P, Ceranowicz P, Galazka K. Chemerin alleviates acute pancreatitis in the rat thorough modulation of NF-κB signal. Pancreatology 2019; 19(3): 401-8.

Owen BM, Mangelsdorf DJ, Kliewer SA. Tissue-specific actions of the metabolic hormones FGF15/19 and FGF21. Trends Endocrinol Metab 2015; 26(1): 22-9.

Ogawa Y, Kurosu H, Yamamoto M, Nandi A, Rosenblatt KP, Goetz R, Eliseenkova AV, Mohammadi M, Kuro-o M. BetaKlotho is required for metabolic activity of fibroblast growth factor 21. Proc Natl Acad Sci U S A 2007; 104(18): 7432-7.

Cuevas-Ramos D, Mehta R, Aguilar-Salinas CA. Fibroblast growth factor 21 and browning of white adipose tissue. Front Physiol 2019; 10: 37.

Lin Z, Tian H, Lam KS, Lin S, Hoo RC, Konishi M, Itoh N, Wang Y, Bornstein SR, Xu A, Li X. Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice. Cell Metab 2013; 17(5): 779–89.

Chen Q, Li J, Ma J, Yang X, Ni M, Zhang Y, Li X, Lin Z, Gong F. Fibroblast growth factor 21 alleviates acute pancreatitis via activation of the Sirt1-autophagy signalling pathway. J Cell Mol Med 2020; 24(9): 5341-51.

Hernandez G, Luo T, Javed TA, Wen L, Kalwat MA, Vale K, Ammouri F, Husain SZ, Kliewer SA, Mangelsdorf DJ. Pancreatitis is an FGF21-deficient state that is corrected by replacement therapy. Sci Transl Med 2020; 12(525): eaay5186.

Shenoy VK, Beaver KM, Fisher FM, Singhal G, Dushay JR, Maratos-Flier E, Flier SN. Elevated serum fibroblast growth factor 21 in humans with acute pancreatitis. PLoS One 2016; 11(11): e0164351.

Icer MA, Gezmen-Karadag M. The multiple functions and mechanisms of osteopontin. Clin Biochem 2018; 59: 17-24.

Clemente N, Raineri D, Cappellano G, Boggio E, Favero F, Soluri MF, Dianzani C, Comi C, Dianzani U, Chiocchetti A. Osteopontin Bridging Innate and Adaptive Immunity in Autoimmune Diseases. J Immunol Res 2016; 2016: 7675437.

Kazanecki CC, Uzwiak DJ, Denhardt DT. Control of osteopontin signaling and function by post‐translational phosphorylation and protein folding. J Cell Biochem 2007; 102(4): 912-24.

Omar B, Banke E, Guirguis E, Åkesson L, Manganiello V, Lyssenko V, Groop L, Gomez MF, Degerman E. Regulation of the pro-inflammatory cytokine osteopontin by GIP in adipocytes--a role for the transcription factor NFAT and phosphodiesterase 3B. Biochem Biophys Res Commun 2012; 425(4): 812-7.

Frangogiannis NG. Matricellular proteins in cardiac adaptation and disease. Physiol Rev 2012; 92(2): 635-88.

Mazzali M, Kipari T, Ophascharoensuk V, Wesson JA, Johnson R, Hughes J. Osteopontin--a molecule for all seasons. QJM 2002; 95(1): 3-13.

Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Jansson M, Zawaideh S, Rittling SR, Denhardt DT, Glimcher MJ, Cantor H. Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 2000; 287(5454): 860-4.

Gimba ER, Tilli TM. Human osteopontin splicing isoforms: known roles, potential clinical applications and activated signaling pathways. Cancer Lett 2013; 331(1): 11-7.

Wirestam L, Nyberg PB, Dzhendov T, Gasslander T, Sandström P, Sjöwall C, Björnsson B. Plasma Osteopontin Reflects Tissue Damage in Acute Pancreatitis. Biomedicines 2023; 11(6): 1627.

Swärd P, Bertilsson S, Struglics A, Kalaitzakis E. Serum Osteopontin Is Associated with Organ Failure in Patients with Acute Pancreatitis. Pancreas 2018; 47(3): e7-10.

Lin RH, Lin Y. Study on the correlation between serum visfatin and SOD in patients with carotid atherosclerosis. Exp Lab Med 2018; 36: 539-40.

Kumari B, Yadav UCS. Adipokine Visfatin's Role in Pathogenesis of Diabesity and Related Metabolic Derangements. Curr Mol Med 2018; 18(2): 116-25.

Mao H, Li Y, Hu Y. Changes of serum high mobility group box-1, heat shock protein 70, ghrelin and visfatin levels and its clinical significance in patients with severe acute pancreatitis. Acta Medica Mediterr 2020; 36(3): 1533-7.

Daniel P, Leśniowski B, Mokrowiecka A, Jasińska A, Pietruczuk M, Małecka-Panas E. Circulating levels of visfatin, resistin and pro-inflammatory cytokine interleukin-8 in acute pancreatitis. Pancreatology 2010; 10(4): 477-82.

Horiuchi T, Mitoma H, Harashima SI, Tsukamoto H, Shimoda T. Transmembrane TNF-α: structure, function and interaction with anti-TNF agents. Rheumatology 2010; 49(7): 1215-28.

Sethi JK, Hotamisligil GS. Metabolic messengers: tumour necrosis factor. Nature Metab 2021; 3(10): 1302-12.

Malleo G, Mazzon E, Siriwardena AK, Cuzzocrea S. Role of tumor necrosis factor-alpha in acute pancreatitis: from biological basis to clinical evidence. Shock 2007; 28(2): 130-40.

Alsfasser G, Antoniu B, Thayer SP, Warshaw AL, Fernandez-del Castillo C. Degradation and inactivation of plasma tumor necrosis factor-alpha by pancreatic proteases in experimental acute pancreatitis. Pancreatology 2005; 5(1): 37-43.

Grewal HP, el Din AM, Gaber L, Kotb M, Gaber AO. Amelioration of the physiologic and biochemical changes of acute pancreatitis using an anti-TNF-α polyclonal antibody. Am J Surg 1994; 167(1): 214-9.

Hughes CB, Grewal HP, Gaber LW, Kotb M, Mann L, Gaber AO. Anti-TNFα therapy improves survival and ameliorates the pathophysiologic sequelae in acute pancreatitis in the rat. Am J Surg 1996; 171(2): 274-80.

Malka D, Vasseur S, Bödeker H, Ortiz EM, Dusetti NJ, Verrando P, Dagorn JC, Iovanna JL. Tumor necrosis factor α triggers antiapoptotic mechanisms in rat pancreatic cells through pancreatitis-associated protein I activation. Gastroenterology 2000; 119(3): 816-28.

Kıyıcı A, İbiş M, Akbulut Ş, Köklü S, Uçar E, Ünlü A. Serum TNF-alpha levels in acute and chronic pancreatitis. Eur J Gen Med 2009; 6(2): 103-7.

Osman MO, Jacobsen NO, Kristensen JU, Larsen CG, Jensen SL. Beneficial effects of hydrocortisone in a model of experimental acute pancreatitis. Digestive Surgery 1999; 16(3): 214-21.

Charalabopoulos A, Davakis S, Lambropoulou M, Papalois A, Simopoulos C, Tsaroucha A. Apigenin exerts anti-inflammatory effects in an experimental model of acute pancreatitis by down-regulating TNF-α. In Vivo 2019; 33(4): 1133-41.

Zhang FH, Sun YH, Fan KL, Dong XB, Han N, Zhao H, Kong L. Protective effects of heme oxygenase-1 against severe acute pancreatitis via inhibition of tumor necrosis factor-α and augmentation of interleukin-10. BMC Gastroenterol 2017; 17(1): 100.

Steinhoff JS, Lass A, Schupp M. Retinoid Homeostasis and Beyond: How Retinol Binding Protein 4 Contributes to Health and Disease. Nutrients 2022; 14(6): 1236.

Klisic A, Kavaric N, Jovanovic M, Soldatovic I, Gligorovic-Barhanovic N, Kotur-Stevuljevic J. Bioavailable testosterone is independently associated with fatty liver index in postmenopausal women. Arch Med Sci 2017;5(13):1188-96.

Klisic A, Kavaric N, Kotur-Stevuljevic J, Ninic A. Serum soluble transferrin receptor levels are independently associated with homeostasis model assessment of insulin resistance in adolescent girls. Arch Med Sci 2023; 19(4): 987–94.

Klisic A, Kavaric N, Ninic A. Retinol-binding protein 4 versus albuminuria as predictors of estimated GFR decline in patients with type 2 diabetes. J Res Med Sci 2018; 23: 44.

Klisic A, Kavaric N, Soldatovic I, Ninic A, Kotur-Stevuljevic J. Retinol-binding protein 4 better correlates with metabolic syndrome than cystatin C. J Lab Med 2019; 43(1): 29-34.

Han X, Ni J, Li B, Bao J, Wan R, Hu G, Chen C. Predictive value of serum retinol binding protein in severity and complications of acute pancreatitis: a retrospective cohort study. Scand J Gastroenterol 2023: 1-8. doi: 10.1080/00365521.2023.2249570.

Singh RG, Pendharkar SA, Plank LD, Petrov MS. Role of human lipocalin proteins in abdominal obesity after acute pancreatitis. Peptides 2017; 91: 1-7.

Singh RG, Pendharkar SA, Gillies NA, Miranda-Soberanis V, Plank LD, Petrov MS. Associations between circulating levels of adipocytokines and abdominal adiposity in patients after acute pancreatitis. Clin Exp Med 2017; 17(4): 477-87.

Klisic A, Kavaric N, Bjelakovic B, Soldatovic I, Martinovic M, Kotur-Stevuljevic J. The association between retinol-binding protein 4 and cardiovascular risk score is mediated by waist circumference in overweight/obese adolescent girls. Acta Clin Croat 2017; 56: 92-8.

Meher S, Mishra TS, Sasmal PK, Rath S, Sharma R, Rout B, Sahu MK. Role of Biomarkers in Diagnosis and Prognostic Evaluation of Acute Pancreatitis. J Biomark 2015; 2015: 519534.

Singh RG, Nguyen NN, Cervantes A, Kim JU, Stuart CE, Petrov MS. Circulating levels of lipocalin-2 are associated with fatty pancreas but not fatty liver. Peptides 2019; 119: 170117.

Chakraborty S, Kaur S, Muddana V, Sharma N, Wittel UA, Papachristou GI, Whitcomb D, Brand RE, Batra SK. Elevated serum neutrophil gelatinase-associated lipocalin is an early predictor of severity and outcome in acute pancreatitis. Am J Gastroenterol 2010; 105(9): 2050-9.

Siddappa PK, Kochhar R, Sarotra P, Medhi B, Jha V, Gupta V. Neutrophil gelatinase-associated lipocalin: An early biomarker for predicting acute kidney injury and severity in patients with acute pancreatitis. JGH Open 2018; 3(2): 105-10.

Lipinski M, Rydzewska-Rosolowska A, Rydzewski A, Rydzewska G. Urinary neutrophil gelatinase-associated lipocalin as an early predictor of disease severity and mortality in acute pancreatitis. Pancreas 2015; 44(3): 448-52.

Jaberi SA, Cohen A, D'Souza C, Abdulrazzaq YM, Ojha S, Bastaki S, Adeghate EA. Lipocalin-2: Structure, function, distribution and role in metabolic disorders. Biomed Pharmacother 2021; 142: 112002.

Lőrincz H, Somodi S, Ratku B, Harangi M, Paragh G. Crucial Regulatory Role of Organokines in Relation to Metabolic Changes in Non-Diabetic Obesity. Metabolites 2023; 13(2): 270.

Phalitakul S, Okada M, Hara Y, Yamawaki H. Vaspin prevents TNF-α-induced intracellular adhesion molecule-1 via inhibiting reactive oxygen species-dependent NF-κB and PKCθ activation in cultured rat vascular smooth muscle cells. Pharmacol Res 2011; 64(5): 493-500.

Zieger K, Weiner J, Krause K, Schwarz M, Kohn M, Stumvoll M, Blüher M, Heiker JT. Vaspin suppresses cytokine-induced inflammation in 3T3-L1 adipocytes via inhibition of NFκB pathway. Mol Cell Endocrinol 2018; 460: 181-8.

Singh RG, Pendharkar SA, Cervantes A, Cho J, Miranda-Soberanis V, Petrov MS. Abdominal obesity and insulin resistance after an episode of acute pancreatitis. Dig Liver Dis 2018; 50(10): 1081-7.

Gao JH, Zeng MY, Yu XH, Zeng GF, He LH, Zheng XL, Zhang DW, Ouyang XP, Tang CK. Visceral adipose tissue-derived serine protease inhibitor accelerates cholesterol efflux by up-regulating ABCA1 expression via the NF-κB/miR-33a pathway in THP-1 macropahge-derived foam cells. Biochem Biophys Res Commun 2018; 500(2): 318-24.

Kadoglou NPE, Kassimis G, Patsourakos N, Kanonidis I, Valsami G. Omentin-1 and vaspin serum levels in patients with pre-clinical carotid atherosclerosis and the effect of statin therapy on them. Cytokine 2021; 138: 155364.

Hussein AA, Ahmed NA, Sakr HI, Atia T, Ahmed OM. Omentin roles in physiology and pathophysiology: an up-to-date comprehensive review. Arch Physiol Biochem 2023; 1-14. doi: 10.1080/13813455.2023.2283685.

Zhang Q, Chen S, Ke Y, Li Q, Shen C, Ruan Y, Wu K, Hu J, Liu S. Association of circulating omentin level and metabolic-associated fatty liver disease: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2023; 14: 1073498.

Sit M, Aktas G, Yilmaz EE, Alcelik A, Terzi EH, Tosun M. Effects of the inflammatory response on serum omentin levels in early acute and chronic pancreatitis. Clin Ter 2014; 165(2): e148-52.

McKenzie SJ, Premkumar R, Askelund KJ, Pendharkar SA, Phillips AR, Windsor JA, Petrov MS. The effect of enteral nutrition on adipokines in patients with acute pancreatitis. J Nutr Sci 2015; 4: e33.

Farrag M, Ait Eldjoudi D, González-Rodríguez M, Cordero-Barreal A, Ruiz-Fernández C, Capuozzo M, González-Gay MA, Mera A, Lago F, Soffar A, Essawy A, Pino J, Farrag Y, Gualillo O. Asprosin in health and disease, a new glucose sensor with central and peripheral metabolic effects. Front Endocrinol (Lausanne) 2023; 13:1101091.

Hoffmann JG, Xie W, Chopra AR. Energy Regulation Mechanism and Therapeutic Potential of Asprosin. Diabetes 2020; 69(4): 559-66.

Tafere GG, Wondafrash DZ, Zewdie KA, Assefa BT, Ayza MA. Plasma Adipsin as a Biomarker and Its Implication in Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes 2020;13:1855-1861.

Milek M, Moulla Y, Kern M, Stroh C, Dietrich A, Schön MR, Gärtner D, Lohmann T, Dressler M, Kovacs P, Stumvoll M, Blüher M, Guiu-Jurado E. Adipsin Serum Concentrations and Adipose Tissue Expression in People with Obesity and Type 2 Diabetes. Int J Mol Sci 2022; 23(4): 2222.

Klimontov VV, Bulumbaeva DM, Bgatova NP, et al. Serum adipokine concentrations in patients with type 2 diabetes: the relationships with distribution, hypertrophy and vascularization of subcutaneous adipose tissue. Diabetes mellitus 2019; 22(4): 336–47.

Antushevich H, Wójcik M. Review: Apelin in disease. Clin Chim Acta 2018; 483: 241-8.

Han S, Englander EW, Gomez GA, Aronson JF, Rastellini C, Garofalo RP, Kolli D, Quertermous T, Kundu R, Greeley GH Jr. Pancreatitis activates pancreatic apelin-APJ axis in mice. Am J Physiol Gastrointest Liver Physiol 2013; 305(2): G139-50.

Han S, Englander EW, Gomez GA, Greeley GH Jr. Apelin Regulates Nuclear Factor-κB's Involvement in the Inflammatory Response of Pancreatitis. Pancreas 2017; 46(1): 64-70.

Nicoletto BB, Sarmento RA, Pedrollo EF, Krolikowski TC, Canani LH. Association between progranulin serum levels and dietary intake. PLoS One 2018; 13(8): e0202149.

Kim HK, Shin MS, Youn BS, Namkoong C, Gil SY, Kang GM, et al. Involvement of progranulin in hypothalamic glucose sensing and feeding regulation. Endocrinology 2011; 152:4672–82.

Adipokini i njihova uloga u akutnom pankreatitisu

Adipokini u akutnom pankreatitisu

Sažetak

Reference