Skip to main content
Top
Published in: BMC Endocrine Disorders 1/2021

Open Access 01-12-2021 | Macroalbuminuria | Research article

Deterioration of diabetic nephropathy via stimulating secretion of cytokines by atrial natriuretic peptide

Authors: Chenxiao Liu, Qi Li, Xiu Feng, Jian Zhu, Qian Li

Published in: BMC Endocrine Disorders | Issue 1/2021

Login to get access

Abstract

Background

Atrial natriuretic peptide (ANP) is a cardiovascular and metabolic hormone that has been identified recently as being associated with chronic kidney disease (CKD) without diabetes. Cytokines such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and adiponectin (ADP) contribute to the development of type 2 diabetes (T2DM). The aim here was to investigate the relationships of ANP with cytokine levels and clinical variables in T2DM nephropathy patients.

Methods

A total of 81 participants with T2DM were recruited, including 37 patients with normoalbuminuria, 23 patients with microalbuminuria and 21 patients with macroalbuminuria. Serum concentrations of ANP and cytokines were measured using enzyme-linked immunosorbent assay (ELISA) kits. The correlations between ANP and clinical variables were analyzed. Multiple linear regression and logistic regression models were constructed to test the associations between ANP and the severity and presence of albuminuria.

Results

The macroalbuminuria patients exhibited higher plasma levels of ANP, TNF-α, IL-6, and ADP; higher serum creatinine (Cr) and blood urea nitrogen (BUN); and longer duration of diabetes mellitus (DM) than the patients with normoalbuminuria and microalbuminuria. Plasma ANP level was significantly associated with TNF-α (r = 0.876, p < 0.001), IL-6 (r = 0.816, p < 0.001) and ADP (r = 0.772, p < 0.001), independent of the duration of DM or the BUN concentration.

Conclusion

ANP is higher in type 2 diabetes mellitus nephropathy subjects, especially those who have macroalbuminuria, which is associated with compensatory responses to inflammation.
Literature
1.
go back to reference Kausik U, Julia BL. Update on diabetic nephropathy: Core curriculum 2018. Am J Kidney Dis. 2018;71(6):884–95.CrossRef Kausik U, Julia BL. Update on diabetic nephropathy: Core curriculum 2018. Am J Kidney Dis. 2018;71(6):884–95.CrossRef
2.
go back to reference Annabelle MW, Søren TK, Mark EC. Diabetic nephropathy: an insight into molecular mechanisms and emerging therapies. Expert Opin Ther Targets. 2019;23(7):579–91.CrossRef Annabelle MW, Søren TK, Mark EC. Diabetic nephropathy: an insight into molecular mechanisms and emerging therapies. Expert Opin Ther Targets. 2019;23(7):579–91.CrossRef
3.
go back to reference Rui T, You MA, Hye YK, Yun JL, Kyung WC, Dae GK, et al. Atrial secretion of ANP is suppressed in renovascular hypertension: shifting of ANP secretion from atria to the left ventricle. Am J Physiol Heart Circ Physiol. 2018;315(3):H590–601.CrossRef Rui T, You MA, Hye YK, Yun JL, Kyung WC, Dae GK, et al. Atrial secretion of ANP is suppressed in renovascular hypertension: shifting of ANP secretion from atria to the left ventricle. Am J Physiol Heart Circ Physiol. 2018;315(3):H590–601.CrossRef
4.
go back to reference Chiaki NO, Kenji K, Naoto M. Three molecular forms of atrial natriuretic peptides: quantitative analysis and biological characterization. J Pept Sci. 2017;23(7–8):486–95. Chiaki NO, Kenji K, Naoto M. Three molecular forms of atrial natriuretic peptides: quantitative analysis and biological characterization. J Pept Sci. 2017;23(7–8):486–95.
5.
go back to reference Tomoko I, John CB. Atrial natriuretic peptide - old but new therapeutic in cardiovascular diseases. Circ J. 2017;81(7):913–9.CrossRef Tomoko I, John CB. Atrial natriuretic peptide - old but new therapeutic in cardiovascular diseases. Circ J. 2017;81(7):913–9.CrossRef
6.
go back to reference Franziska T, Qingyu W. ANP-induced signaling cascade and its implications in renal pathophysiology. Am J Physiol Renal Physiol. 2015;308(10):F1047–55.CrossRef Franziska T, Qingyu W. ANP-induced signaling cascade and its implications in renal pathophysiology. Am J Physiol Renal Physiol. 2015;308(10):F1047–55.CrossRef
7.
go back to reference Spanaus KS, Kronenberg F, Ritz E, Schlapbach R, Fliser D, Hersberger M, et al. Mild-to-moderate kidney disease study G: B-type natriuretic peptide concentrations predict the progression of nondiabetic chronic kidney disease: the mild-to-moderate kidney disease study. Clin Chem. 2007;53(7):1264–72.CrossRef Spanaus KS, Kronenberg F, Ritz E, Schlapbach R, Fliser D, Hersberger M, et al. Mild-to-moderate kidney disease study G: B-type natriuretic peptide concentrations predict the progression of nondiabetic chronic kidney disease: the mild-to-moderate kidney disease study. Clin Chem. 2007;53(7):1264–72.CrossRef
8.
go back to reference Wang Y, Xu L, Yuan L, Li D, Zhang Y, Zheng R, et al. Sodium-glucose co-transporter-2 inhibitors suppress atrial natriuretic peptide secretion in patients with newly diagnosed type 2 diabetes. Diabetic Med. 2016;33(12):1732–6.CrossRef Wang Y, Xu L, Yuan L, Li D, Zhang Y, Zheng R, et al. Sodium-glucose co-transporter-2 inhibitors suppress atrial natriuretic peptide secretion in patients with newly diagnosed type 2 diabetes. Diabetic Med. 2016;33(12):1732–6.CrossRef
9.
go back to reference Robert W. O'R. Adipose tissue and the physiologic underpinnings of metabolic disease. Surg Obes Relat Dis. 2018;14(11):1755–63.CrossRef Robert W. O'R. Adipose tissue and the physiologic underpinnings of metabolic disease. Surg Obes Relat Dis. 2018;14(11):1755–63.CrossRef
10.
go back to reference Ravindran J, Rajeswari R, Sugapriya D. Emerging Role of Adipocytokines in Type 2 Diabetes as Mediators of Insulin Resistance and Cardiovascular Disease. Can J Diabetes. 2018;42(4):446–456.e1.CrossRef Ravindran J, Rajeswari R, Sugapriya D. Emerging Role of Adipocytokines in Type 2 Diabetes as Mediators of Insulin Resistance and Cardiovascular Disease. Can J Diabetes. 2018;42(4):446–456.e1.CrossRef
11.
go back to reference Ze FC, Yulan B, Xin YL, Qian QL, Zheng W, Yuan FL, et al. Effects of Adiponectin on T2DM and glucose homeostasis: a Mendelian randomization study. Diabetes Metab Syndr Obes. 2020;13:1771–84.CrossRef Ze FC, Yulan B, Xin YL, Qian QL, Zheng W, Yuan FL, et al. Effects of Adiponectin on T2DM and glucose homeostasis: a Mendelian randomization study. Diabetes Metab Syndr Obes. 2020;13:1771–84.CrossRef
12.
go back to reference Jun YL, Jae WY, Byoung GH, Seung OC, Jae SK. Adiponectin for the treatment of diabetic nephropathy. Korean J Intern Med. 2019;34(3):480–91.CrossRef Jun YL, Jae WY, Byoung GH, Seung OC, Jae SK. Adiponectin for the treatment of diabetic nephropathy. Korean J Intern Med. 2019;34(3):480–91.CrossRef
13.
go back to reference Wei Y, Qian OY. Adiponectin improves diabetic nephropathy by inhibiting necrotic apoptosis. Arch Med Sci. 2019;15(5):1321–8.CrossRef Wei Y, Qian OY. Adiponectin improves diabetic nephropathy by inhibiting necrotic apoptosis. Arch Med Sci. 2019;15(5):1321–8.CrossRef
14.
go back to reference Andrea T, Federica V, Miriam P, Marco G, Laura S, Roberto B, et al. Adipose tissue, obesity and Adiponectin: role in endocrine Cancer risk. Int J Mol Sci. 2019;20(12):2863.CrossRef Andrea T, Federica V, Miriam P, Marco G, Laura S, Roberto B, et al. Adipose tissue, obesity and Adiponectin: role in endocrine Cancer risk. Int J Mol Sci. 2019;20(12):2863.CrossRef
15.
go back to reference Bordicchia M, Liu D, Amri EZ, Ailhaud G, Dessi-Fulgheri P, Zhang C, et al. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J Clin Invest. 2012;122(3):1022–36.CrossRef Bordicchia M, Liu D, Amri EZ, Ailhaud G, Dessi-Fulgheri P, Zhang C, et al. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J Clin Invest. 2012;122(3):1022–36.CrossRef
16.
go back to reference Moro C, Klimcakova E, Lolmede K, Berlan M, Lafontan M, Stich V, et al. Atrial natriuretic peptide inhibits the production of adipokines and cytokines linked to inflammation and insulin resistance in human subcutaneous adipose tissue. Diabetologia. 2007;50(5):1038–47.CrossRef Moro C, Klimcakova E, Lolmede K, Berlan M, Lafontan M, Stich V, et al. Atrial natriuretic peptide inhibits the production of adipokines and cytokines linked to inflammation and insulin resistance in human subcutaneous adipose tissue. Diabetologia. 2007;50(5):1038–47.CrossRef
17.
go back to reference Paul ES, Adeera L. Valuation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013;158(11):825–30.CrossRef Paul ES, Adeera L. Valuation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013;158(11):825–30.CrossRef
18.
go back to reference Lampropoulou IT, Stangou M, Papagianni A, Didangelos T, Iliadis F, Efstratiadis G. TNF-alpha and microalbuminuria in patients with type 2 diabetes mellitus. J Diabetes Res. 2014;2014:394206.CrossRef Lampropoulou IT, Stangou M, Papagianni A, Didangelos T, Iliadis F, Efstratiadis G. TNF-alpha and microalbuminuria in patients with type 2 diabetes mellitus. J Diabetes Res. 2014;2014:394206.CrossRef
19.
go back to reference Bin C, Meiyan W, Chongsen Z, Yan HL, Zhong GX. Association between IL-6 polymorphisms and diabetic nephropathy risk: a Meta-analysis. Am J Med Sci. 2019;358(5):363–73.CrossRef Bin C, Meiyan W, Chongsen Z, Yan HL, Zhong GX. Association between IL-6 polymorphisms and diabetic nephropathy risk: a Meta-analysis. Am J Med Sci. 2019;358(5):363–73.CrossRef
20.
go back to reference Ming Z, Jungang H. Dendrobium Officinale Kimura et Migo ameliorates insulin resistance in rats with diabetic nephropathy. Med Sci Monit Basic Res. 2018;24:84–92. Ming Z, Jungang H. Dendrobium Officinale Kimura et Migo ameliorates insulin resistance in rats with diabetic nephropathy. Med Sci Monit Basic Res. 2018;24:84–92.
21.
go back to reference Zietse R, Schalekamp MA. Effect of synthetic human atrial natriuretic peptide (102-126) in nephrotic syndrome. Kidney Int. 1988;34(5):717–24.CrossRef Zietse R, Schalekamp MA. Effect of synthetic human atrial natriuretic peptide (102-126) in nephrotic syndrome. Kidney Int. 1988;34(5):717–24.CrossRef
22.
go back to reference Franziska T, Qing YW. ANP-induced signaling cascade and its implications in renal. Am J Physiol Renal Physiol. 2015;308(10):F1047–55 pathophysiology.CrossRef Franziska T, Qing YW. ANP-induced signaling cascade and its implications in renal. Am J Physiol Renal Physiol. 2015;308(10):F1047–55 pathophysiology.CrossRef
23.
go back to reference Desai AS, Toto R, Jarolim P, Uno H, Eckardt KU, Kewalramani R, et al. Association between cardiac biomarkers and the development of ESRD in patients with type 2 diabetes mellitus, anemia, and CKD. Am J Kidney Dis. 2011;58(5):717–28.CrossRef Desai AS, Toto R, Jarolim P, Uno H, Eckardt KU, Kewalramani R, et al. Association between cardiac biomarkers and the development of ESRD in patients with type 2 diabetes mellitus, anemia, and CKD. Am J Kidney Dis. 2011;58(5):717–28.CrossRef
24.
go back to reference Yang G, Donna T, Jie X, David FL, John AM, Danielle BC, et al. Aberrant pro-atrial natriuretic peptide/corin/natriuretic peptide receptor signaling is present in maternal vascular endothelium in preeclampsia. Pregnancy Hypertens. 2018;11:1–6.CrossRef Yang G, Donna T, Jie X, David FL, John AM, Danielle BC, et al. Aberrant pro-atrial natriuretic peptide/corin/natriuretic peptide receptor signaling is present in maternal vascular endothelium in preeclampsia. Pregnancy Hypertens. 2018;11:1–6.CrossRef
25.
go back to reference Motoyuki I, Seiji M, Takeshi O, Jun S, Shin YK, Ryui CA, et al. Arterial stiffness, physical activity, and atrial natriuretic peptide gene polymorphism in older subjects. Hypertens Res. 2008;31(4):767–74.CrossRef Motoyuki I, Seiji M, Takeshi O, Jun S, Shin YK, Ryui CA, et al. Arterial stiffness, physical activity, and atrial natriuretic peptide gene polymorphism in older subjects. Hypertens Res. 2008;31(4):767–74.CrossRef
26.
go back to reference Chen C, Hui XL, Cheng CT, Dou DT, Yong XZ, Xia L, et al. Mutation in NPPA causes atrial fibrillation by activating inflammation and cardiac fibrosis in a knock-in rat model. FASEB J. 2019;33(8):8878–91.CrossRef Chen C, Hui XL, Cheng CT, Dou DT, Yong XZ, Xia L, et al. Mutation in NPPA causes atrial fibrillation by activating inflammation and cardiac fibrosis in a knock-in rat model. FASEB J. 2019;33(8):8878–91.CrossRef
27.
go back to reference Li BM, Jin RZ, Bi WM, Chang MW, Ya BS, Meng Z, et al. ANP/NPRA signaling preferentially mediates Th2 responses in favor of pathological processes during the course of acute allergic asthma. Int J Clin Exp Med. 2015;8(4):5121–8. Li BM, Jin RZ, Bi WM, Chang MW, Ya BS, Meng Z, et al. ANP/NPRA signaling preferentially mediates Th2 responses in favor of pathological processes during the course of acute allergic asthma. Int J Clin Exp Med. 2015;8(4):5121–8.
28.
go back to reference Vanessa V, David S, Khanh L, Bruce KW, Baljit S. Mouse model to study pulmonary intravascular macrophage recruitment and lung inflammation in acute necrotizing pancreatitis. Cell Tissue Res. 2019;378(1):97–111.CrossRef Vanessa V, David S, Khanh L, Bruce KW, Baljit S. Mouse model to study pulmonary intravascular macrophage recruitment and lung inflammation in acute necrotizing pancreatitis. Cell Tissue Res. 2019;378(1):97–111.CrossRef
29.
go back to reference Gupta C, Bubber P, Fahim M, Saidullah B, Omanwar S. Adiponectin in onset and progression of T2DM with cardiac dysfunction in rats. Hum Exp Toxicol. 2020;39(11):1463–74.CrossRef Gupta C, Bubber P, Fahim M, Saidullah B, Omanwar S. Adiponectin in onset and progression of T2DM with cardiac dysfunction in rats. Hum Exp Toxicol. 2020;39(11):1463–74.CrossRef
30.
go back to reference Chen XL, Xiu F, Qi L, Ying W, Qian L, Jian MH. Adiponectin, TNF-α and inflammatory cytokines and risk of type 2 diabetes: a systematic review and meta-analysis. Cytokin. 2016;86:100–9. Chen XL, Xiu F, Qi L, Ying W, Qian L, Jian MH. Adiponectin, TNF-α and inflammatory cytokines and risk of type 2 diabetes: a systematic review and meta-analysis. Cytokin. 2016;86:100–9.
31.
go back to reference Wei L, Xiang HZ, Yu FL, Si MZ, Xiao LC, Rui Z, et al. Serum leptin, resistin, and adiponectin levels in obese and non-obese patients with newly diagnosed type 2 diabetes mellitus: a population-based study. Medicine (Baltimore). 2020;99(6):e19052.CrossRef Wei L, Xiang HZ, Yu FL, Si MZ, Xiao LC, Rui Z, et al. Serum leptin, resistin, and adiponectin levels in obese and non-obese patients with newly diagnosed type 2 diabetes mellitus: a population-based study. Medicine (Baltimore). 2020;99(6):e19052.CrossRef
32.
go back to reference Ran J, Xiong X, Liu W, Guo S, Li Q, Zhang R, et al. Increased plasma adiponectin closely associates with vascular endothelial dysfunction in type 2 diabetic patients with diabetic nephropathy. Diabetes Res Clin Pract. 2010;88(2):177–83.CrossRef Ran J, Xiong X, Liu W, Guo S, Li Q, Zhang R, et al. Increased plasma adiponectin closely associates with vascular endothelial dysfunction in type 2 diabetic patients with diabetic nephropathy. Diabetes Res Clin Pract. 2010;88(2):177–83.CrossRef
33.
go back to reference Souza SC, Chau MD, Yang Q, Gauthier MS, Clairmont KB, Wu Z, et al. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK. Biochem Biophys Res Commun. 2011;410(3):398–403.CrossRef Souza SC, Chau MD, Yang Q, Gauthier MS, Clairmont KB, Wu Z, et al. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK. Biochem Biophys Res Commun. 2011;410(3):398–403.CrossRef
34.
go back to reference Birkenfeld AL, Boschmann M, Engeli S, Moro C, Arafat AM, Luft FC, et al. Atrial natriuretic peptide and adiponectin interactions in man. PLoS One. 2012;7(8):e43238.CrossRef Birkenfeld AL, Boschmann M, Engeli S, Moro C, Arafat AM, Luft FC, et al. Atrial natriuretic peptide and adiponectin interactions in man. PLoS One. 2012;7(8):e43238.CrossRef
35.
go back to reference Tanaka T, Tsutamoto T, Sakai H, Nishiyama K, Fujii M, Yamamoto T, et al. Effect of atrial natriuretic peptide on adiponectin in patients with heart failure. Eur J Heart Fail. 2008;10(4):360–6.CrossRef Tanaka T, Tsutamoto T, Sakai H, Nishiyama K, Fujii M, Yamamoto T, et al. Effect of atrial natriuretic peptide on adiponectin in patients with heart failure. Eur J Heart Fail. 2008;10(4):360–6.CrossRef
36.
go back to reference Barutta F, Bruno G, Grimaldi S, Gruden G. Inflammation in diabetic nephropathy: moving toward clinical biomarkers and targets for treatment. Endocrine. 2015;48(3):730–42.CrossRef Barutta F, Bruno G, Grimaldi S, Gruden G. Inflammation in diabetic nephropathy: moving toward clinical biomarkers and targets for treatment. Endocrine. 2015;48(3):730–42.CrossRef
37.
go back to reference Verspohl EJ, Bernemann IK. Atrial natriuretic peptide ()-induced inhibition of glucagon secretion: mechanism of action in isolated rat pancreatic islets. Peptides. 1996;17(6):1023–9.CrossRef Verspohl EJ, Bernemann IK. Atrial natriuretic peptide ()-induced inhibition of glucagon secretion: mechanism of action in isolated rat pancreatic islets. Peptides. 1996;17(6):1023–9.CrossRef
38.
go back to reference Sabrina U, Julia K, Jelena S, Martina D, Peter KD, Gisela D. Atrial natriuretic peptide affects stimulus-secretion coupling of pancreatic β-cells. Diabetes. 2017;66(11):2840–8.CrossRef Sabrina U, Julia K, Jelena S, Martina D, Peter KD, Gisela D. Atrial natriuretic peptide affects stimulus-secretion coupling of pancreatic β-cells. Diabetes. 2017;66(11):2840–8.CrossRef
Metadata
Title
Deterioration of diabetic nephropathy via stimulating secretion of cytokines by atrial natriuretic peptide
Authors
Chenxiao Liu
Qi Li
Xiu Feng
Jian Zhu
Qian Li
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2021
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-021-00867-7

Other articles of this Issue 1/2021

BMC Endocrine Disorders 1/2021 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.