Elsevier

Biomedicine & Pharmacotherapy

Volume 84, December 2016, Pages 1826-1832
Biomedicine & Pharmacotherapy

Review
The role of natriuretic peptides in diabetes and its complications

https://doi.org/10.1016/j.biopha.2016.10.089Get rights and content

Abstract

This review aimed to summarize recent findings on the role of natriuretic peptides (NPs) in diabetes and its important complications. Although the treatment of diabetes mellitus has benefited from recent advances, aggressive glycemic control can increase the risk of hypoglycemia and weight gain. Therefore, innovative therapies are required to address this issue. Natriuretic peptides (NPs) may have such novel therapeutic potential. NPs comprise a family of structurally related peptides, including atrial, brain, C-type, and dendroaspis. Each of these NPs has a wide range of specific functions to regulate and maintain cardiovascular, renal, and endocrine homeostasis. NPs exert their effects by interacting with three receptor subtypes including NPR-A, NPR-B, and NPR-C. The coronary NP system has been suggested to be involved in regulating water and salt balance, as well as vascular remodeling. In this review, we provide evidence that NPs play an important role in diabetes mellitus and its related complications including macrovascular and microvascular disorders. NPs hold promise as markers for early diagnosis, risk assessment, and intervention guidance in diabetes and its complications and may thus improve diabetes care.

Section snippets

Natriuretic peptides and receptors

Natriuretic peptides (NPs) are a family of peptides that have similar sequences and conformations and include atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP) and dendroaspis natriuretic peptide (DNP). NPs are genetically distinct and play a significant role in the maintenance of circulation, renal function and endocrine status [1], [2], [3]. ANP is produced by the heart, whereas pro-ANP is a peptide with 126 amino acids that is stored in

Natriuretic peptides in diabetes and diabetes-related complications

The global burden of diabetes is projected to increase over the next few decades. Type 2 diabetes is projected to occur at a substantially earlier age compared to the present age of onset. The pathogenesis of diabetes is not clear. However, it is acknowledged to be related to insulin resistance, chronic low-grade inflammation, hereditary factors, as well as an unhealthy lifestyle. Diabetes-related complications could lead to increased morbidity, mortality, and enormous health expenditure.

Future perspectives

In the last decade, understanding of the role of NPs in diabetes and its related complications has significantly improved. Although epidemiological studies have confirmed associations between inflammation biomarkers, such as endothelial dysfunction with type 2 diabetes, and complications including diabetic foot and erectile dysfunction, the exact mechanism of the low-grade inflammation state is largely unknown. Previous studies on adult Npr2 mice demonstrated the role of CNP/NPR-B signaling in

Conclusions

NPs play an important role in diabetes and its complications. The use of NPs as tools for early detection, risk assessment, diagnosis, and goal-guided intervention in diabetes and its complications holds great promise for improving diabetes care.

Conflict of interest

The authors declare that they have no conflicts of interest.

Acknowledgments

This study was sponsored by the National Natural Science Foundation of China (81202189) and Natural Science Foundation of Heilongjiang Province (H2016040).

References (89)

  • N. Seki et al.

    Relationship between BNP level and renal function in diabetic nephropathy with microalbuminuria

    J. Diabetes Complicat.

    (2013)
  • S. Del Ry et al.

    Natriuretic peptide system and the heart

    Front. Horm. Res.

    (2014)
  • Y. Akashi et al.

    Atrial natriuretic peptide and related peptides

    Clin. Chem. Lab. Med.

    (2007)
  • S. Rubattu et al.

    Npr-c: a component of the natriuretic peptide family with implications in human diseases

    J. Mol. Med. (Berl)

    (2010)
  • J. Chan et al.

    Hypertension in mice lacking the proatrial natriuretic peptide convertase corin

    Sci. U. S. A.

    (2005)
  • T. Sudoh et al.

    A new natriuretic peptide in porcine brain

    Nature

    (1988)
  • K. Yamamoto et al.

    Superiority of brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy

    Hypertension

    (1996)
  • C.S. Barr et al.

    C-type natriuretic peptide

    Peptides

    (1996)
  • L.R. Potter

    Natriuretic peptide metabolism clearance and degradation

    FEBS J.

    (2011)
  • K. Nakao et al.

    The Local CNP/GC-B system in growth plate is responsible for physiological endochondral bone growth

    Sci. Rep.

    (2015)
  • V.G. Khurana et al.

    A pilot study of dendroaspis natriuretic peptide in aneurysmal subarachnoid hemorrhage

    Neurosurgery

    (2004)
  • H. Bentzen et al.

    Abnormal rhythmic oscillations of atrial natriuretic peptide and brain natriuretic peptide in heart failure

    Clin. Sci. (Lond)

    (2003)
  • C. Sengenes et al.

    Natriuretic peptides: a new lipolytic pathway in human adipocytes

    FASEB J.

    (2000)
  • M.F. Goy et al.

    Evidence for a novel natriuretic peptide receptor that prefers brain natriuretic peptide over atrial natriuretic peptide

    Biochem. J.

    (2001)
  • M. Magnusson et al.

    Low plasma level of atrial natriuretic peptide predicts development of diabetes: the prospective Malmo diet and cancer study

    J. Clin. Endocrinol. Metab.

    (2012)
  • E. Bonora et al.

    Prevalence of IR in metabolic disorders: the Bruneck Study

    Diabetes

    (1998)
  • D.K. Gupta et al.

    Racial differences in circulating natriuretic peptide levels: the atherosclerosis risk in communities study

    J. Am. Heart Assoc.

    (2015)
  • D. Fliser et al.

    Antiinflammatory effects of angiotensin ii subtype 1 receptor blockade in hypertensive patients with microinflammation

    Circulation

    (2004)
  • E.J. Henriksen et al.

    Angiotensin converting enzyme inhibitors and modulation of skeletal muscle insulin resistance

    Diabetes Obesity Metab.

    (2003)
  • J. Janke et al.

    Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin type 1 receptors

    Diabetes

    (2002)
  • A. Prasad et al.

    Renin-angiotensin system and angiotensin receptor blockers in the metabolic syndrome

    Circulation

    (2004)
  • S. Rajagopalan et al.

    Angiotensin ii-mediated hypertension in the rat increases vascular superoxide production via membrane nadh/nadph oxidase activation. Contribution to alterations of vasomotor tone

    J. Clin. Invest.

    (1996)
  • L.A. Velloso et al.

    The multi-faceted cross-talk between the insulin and angiotensin ii signaling systems

    Diabetes Metab. Res. Rev.

    (2006)
  • T. Haak et al.

    The effect of atrial natriuretic peptide on glucose tolerance and insulin level

    Med. Klin. (Munich)

    (1990)
  • G.A. Walford et al.

    Circulating natriuretic peptide concentrations reflect changes in insulin sensitivity over time in the Diabetes Prevention Program

    Diabetologia

    (2014)
  • M. Magnusson et al.

    Low plasma level of atrial natriuretic peptide predicts development of diabetes: the prospective Malmo Diet and Cancer Study

    J. Clin. Endocrinol. Metab.

    (2012)
  • M. Lazo et al.

    NH2-terminal pro-brain natriuretic peptide and risk of diabetes

    Diabetes

    (2013)
  • T.J. Wang et al.

    Association of plasma natriuretic peptide levels with metabolic risk factors in ambulatory individuals

    Circulation

    (2007)
  • F. Anan et al.

    Role of insulin resistance in nondipper essential hypertensive patients

    Hypertens. Res.

    (2003)
  • S. Abouchacra et al.

    Insulin blunts the natriuretic action of atrial natriuretic peptide in hypertension

    Hypertension

    (1994)
  • C. Moro 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)
  • O. Pivovarova et al.

    Insulin up-regulates natriuretic peptide clearance receptor expression in the subcutaneous fat depot in obese subjects: a missing link between cvd risk and obesity?

    J. Clin. Endocrinol. Metab.

    (2012)
  • P.B. Lauria et al.

    Low plasma atrial natriuretic peptide: a new piece in the puzzle of polycystic ovary syndrome

    J. Clin. Endocrinol. Metab.

    (2013)
  • S. Haufe et al.

    Differential response of the natriuretic peptide system to weight loss and exercise in overweight or obese patients

    J. Hypertens.

    (2015)

    • Cited by (7)

    • Potential effects and application prospect of angiotensin receptor-neprilysin inhibitor in diabetic kidney disease

      2022, Journal of Diabetes and its Complications
      Citation Excerpt :

      Insulin sensitivity and insulin secretion were hypothesized to relate to NP secretion, NP receptor expression and the post-receptor signaling.48 Low ANP and BNP may aggravate insulin resistance by activation of renin-angiotensin system, which could downregulate the natriuretic peptide system, blunt the natriuretic action of ANP, and activate the sympathetic nervous system.29,49 Moreover, ANP and BNP could promote adiponectin synthesis by adipocytes and subsequently improve glucose metabolism and insulin resistance by the AMPK signaling pathway.50

    • Circular RNA WDR77 target FGF-2 to regulate vascular smooth muscle cells proliferation and migration by sponging miR-124

      2017, Biochemical and Biophysical Research Communications
      Citation Excerpt :

      In recent years, the morbidity of diabetes mellitus (DM) is gradually increased with millions of newly diagnosed patients all over the world [1,2]. DM could cause numerous complications, such as atherosclerosis, diabetic nephropathy, and diabetic foot gangrene [3,4]. For atherosclerosis, disordered proliferation of vascular smooth muscle cells (VSMCs) plays a vital role in the atherosclerotic procession [5].

    • Prognostication of clinical outcomes in diabetes mellitus: Emerging role of cardiac biomarkers

      2019, Diabetes and Metabolic Syndrome: Clinical Research and Reviews
      Citation Excerpt :

      The aim of the review is to summarize our knowledge regarding predictive role of cardiac biomarkers in T2DM. Natriuretic peptide (NP) system alterations are involved in pathogenesis of diabetes mellitus and its complications including diabetes-induced cardiomyopathy and angiopathy [17]. NPs are released from cardiac myocytes due to stretching, fluid overload, inflammation, and necrosis [18] Therefore, endothelial cells produce C-type of NP in result of microvascular inflammation, atherosclerosis, endothelial dysfunction and thrombosis [19].

    • Challenging and opportunities in clinical implementation of circulating cardiac biomarkers in diabetes mellitus: The narrative review

      2021, AME Medical Journal

    • Midregional pro-atrial natriuretic peptide, an important member of the natriuretic peptide family: potential role in diagnosis and prognosis of cardiovascular disease

      2018, Journal of International Medical Research

    • Diabetes modifies the role of prostanoids and potassium channels which regulate the hypereactivity of the rabbit renal artery to BNP

      2018, Naunyn-Schmiedeberg's Archives of Pharmacology
    View all citing articles on Scopus
    View full text
    © 2016 Elsevier Masson SAS. All rights reserved.