Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway.
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/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes.
Internal Medicine and Geriatrics, Department of Clinical and Molecular Sciences, University "Politecnica delle Marche," Ancona, Italy;
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Bordicchia
Internal Medicine and Geriatrics, Department of Clinical and Molecular Sciences, University "Politecnica delle Marche," Ancona, Italy;
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Ceresiani
Internal Medicine and Geriatrics, Department of Clinical and Molecular Sciences, University "Politecnica delle Marche," Ancona, Italy;
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Pavani
Department of Urology, University Politecnica delle Marche, Ancona, Italy;
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Minardi
Department of Urology, University Politecnica delle Marche, Ancona, Italy;
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Polito
Pediatric Endocrinology and Diabetes, University of Ulm, Ulm, Germany; and.
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Wabitsch
Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
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Cannone
Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
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Burnett
Internal Medicine and Geriatrics, Department of Clinical and Molecular Sciences, University "Politecnica delle Marche," Ancona, Italy; Italian National Research Center on Aging INRCA-IRCCS Ospedale "U. Sestilli";
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Dessì-Fulgheri
Internal Medicine and Geriatrics, Department of Clinical and Molecular Sciences, University "Politecnica delle Marche," Ancona, Italy; Italian National Research Center on Aging INRCA-IRCCS Ospedale "U. Sestilli"; r.sarzani@univpm.it.
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Sarzani
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D045265:Natriuretic Peptides / Q000378:metabolism*; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D045265:Natriuretic Peptides; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C; D005947:Glucose
insulin resistance; insulin-induced genes; lipolysis; natriuretic peptide receptors