Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes

A metabolic link with the cardiac natriuretic pathway

M. Bordicchia, M. Ceresiani, M. Pavani, D. Minardi, M. Polito, M. Wabitsch, V. Cannone, J. C. Burnett, P. Dessì-Fulgheri, R. Sarzani

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucosedependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes.

Original languageEnglish
Pages (from-to)R104-R114
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume311
Issue number1
DOIs
Publication statusPublished - Jul 1 2016

Fingerprint

Natriuretic Peptides
Peptide Receptors
Adipocytes
Insulin
Glucose
Lipolysis
Intra-Abdominal Fat
Fasting
Phosphatidylinositol 3-Kinase
Natriuretic Agents
Kidney
Caloric Restriction
Metabolome
Hyperinsulinism
Atrial Natriuretic Factor
Ambulatory Surgical Procedures
Adipose Tissue
Up-Regulation
Sodium
Hormones

Keywords

  • Insulin resistance
  • Insulin-induced genes
  • Lipolysis
  • Natriuretic peptide receptors

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)
  • Physiology (medical)

Cite this

Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes : A metabolic link with the cardiac natriuretic pathway. / Bordicchia, M.; Ceresiani, M.; Pavani, M.; Minardi, D.; Polito, M.; Wabitsch, M.; Cannone, V.; Burnett, J. C.; Dessì-Fulgheri, P.; Sarzani, R.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 311, No. 1, 01.07.2016, p. R104-R114.

Research output: Contribution to journalArticle

Bordicchia, M. ; Ceresiani, M. ; Pavani, M. ; Minardi, D. ; Polito, M. ; Wabitsch, M. ; Cannone, V. ; Burnett, J. C. ; Dessì-Fulgheri, P. ; Sarzani, R. / Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes : A metabolic link with the cardiac natriuretic pathway. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2016 ; Vol. 311, No. 1. pp. R104-R114.
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