An analogue of atrial natriuretic peptide (C-ANP4-23) modulates glucose metabolism in human differentiated adipocytes

Francisco Javier Ruiz-Ojeda; Concepción María Aguilera; Azahara Iris Rupérez; Ángel Gil; Carolina Gomez-Llorente

doi:10.1016/j.mce.2016.05.011

An analogue of atrial natriuretic peptide (C-ANP4-23) modulates glucose metabolism in human differentiated adipocytes

Mol Cell Endocrinol. 2016 Aug 15:431:101-8. doi: 10.1016/j.mce.2016.05.011. Epub 2016 May 13.

Authors

Francisco Javier Ruiz-Ojeda¹, Concepción María Aguilera², Azahara Iris Rupérez³, Ángel Gil², Carolina Gomez-Llorente⁴

Affiliations

¹ Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain; Institute of Nutrition and Food Technology "José Mataix", Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n, 18016 Armilla, Granada, Spain; Instituto de Investigación Biosanitaria ibs, Granada, Spain.
² Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain; Institute of Nutrition and Food Technology "José Mataix", Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n, 18016 Armilla, Granada, Spain; Instituto de Investigación Biosanitaria ibs, Granada, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Madrid, Spain.
³ Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain; Institute of Nutrition and Food Technology "José Mataix", Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n, 18016 Armilla, Granada, Spain.
⁴ Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain; Institute of Nutrition and Food Technology "José Mataix", Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n, 18016 Armilla, Granada, Spain; Instituto de Investigación Biosanitaria ibs, Granada, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Madrid, Spain. Electronic address: gomezll@ugr.es.

PMID: 27181211
DOI: 10.1016/j.mce.2016.05.011

Abstract

The present study was undertaken to investigate the effects of C-atrial natriuretic peptide (C-ANP4-23) in human adipose-derived stem cells differentiated into adipocytes over 10 days (1 μM for 4 h). The intracellular cAMP, cGMP and protein kinase A levels were determined by ELISA and gene and protein expression were determined by qRT-PCR and Western blot, respectively, in the presence or absence of C-ANP4-23. The levels of lipolysis and glucose uptake were also determined. C-ANP4-23 treatment significantly increased the intracellular cAMP levels and the gene expression of glucose transporter type 4 (GLUT4) and protein kinase, AMP-activated, alpha 1 catalytic subunit (AMPK). Western blot showed a significant increase in GLUT4 and phosphor-AMPKα levels. Importantly, the adenylate cyclase inhibitor SQ22536 abolished these effects. Additionally, C-ANP4-23 increased glucose uptake by 2-fold. Our results show that C-ANP4-23 enhances glucose metabolism and might contribute to the development of new peptide-based therapies for metabolic diseases.

Keywords: Adipocytes; Natriuretic peptide; Natriuretic peptide receptor 3; Obesity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinases / metabolism
Adipocytes / metabolism*
Atrial Natriuretic Factor / metabolism*
Carbohydrate Metabolism / physiology
Cell Differentiation / physiology*
Cells, Cultured
Cyclic AMP / metabolism
Cyclic AMP-Dependent Protein Kinases / metabolism
Cyclic GMP / metabolism
Gene Expression / physiology
Glucose / metabolism*
Glucose Transporter Type 4 / metabolism
Humans
Lipolysis / physiology
Peptide Fragments / metabolism*

Substances

Glucose Transporter Type 4
Peptide Fragments
atrial natriuretic factor (4-23)NH2, de-Gln(18)-de-Ser(19)-de-Gly(20,22)-de-Leu(21)-
Atrial Natriuretic Factor
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
AMP-Activated Protein Kinases
Cyclic GMP
Glucose