β Cell-specific deletion of guanylyl cyclase A, the receptor for atrial natriuretic peptide, accelerates obesity-induced glucose intolerance in mice

Cardiovascular Diabetology
Sabine TauscherMichaela Kuhn

Abstract

The cardiac hormones atrial (ANP) and B-type natriuretic peptides (BNP) moderate arterial blood pressure and improve energy metabolism as well as insulin sensitivity via their shared cGMP-producing guanylyl cyclase-A (GC-A) receptor. Obesity is associated with impaired NP/GC-A/cGMP signaling, which possibly contributes to the development of type 2 diabetes and its cardiometabolic complications. In vitro, synthetic ANP, via GC-A, stimulates glucose-dependent insulin release from cultured pancreatic islets and β-cell proliferation. However, the relevance for systemic glucose homeostasis in vivo is not known. To dissect whether the endogenous cardiac hormones modulate the secretory function and/or proliferation of β-cells under (patho)physiological conditions in vivo, here we generated a novel genetic mouse model with selective disruption of the GC-A receptor in β-cells. Mice with a floxed GC-A gene were bred to Rip-CreTG mice, thereby deleting GC-A selectively in β-cells (β GC-A KO). Weight gain, glucose tolerance, insulin sensitivity, and glucose-stimulated insulin secretion were monitored in normal diet (ND)- and high-fat diet (HFD)-fed mice. β-cell size and number were measured by immunofluorescence-based islet morphometry. In...Continue Reading

References

Nov 1, 1986·Journal of Cardiovascular Pharmacology·D E UehlingerR E Lang
May 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Rita HoltwickMichaela Kuhn
Jun 14, 2002·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·M NannipieriE Ferrannini
Jul 20, 2002·Trends in Molecular Medicine·Melissa K LingohrChristopher J Rhodes
Mar 23, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cedric MoroMichel Berlan
Aug 28, 2004·Diabetes·Emilie GesinaBernadette Breant
Jun 19, 2008·American Journal of Physiology. Endocrinology and Metabolism·Cedric MoroMichel Berlan
Oct 7, 2008·Diabetes·Andreas L BirkenfeldJens Jordan
Jul 30, 2011·Journal of the American College of Cardiology·Valentina CannoneJohn C Burnett
Nov 25, 2011·The Journal of Clinical Endocrinology and Metabolism·Martin MagnussonOlle Melander
Feb 7, 2012·The Journal of Clinical Investigation·Marica BordicchiaSheila Collins
Nov 13, 2013·Diabetes·Teresa MezzaRohit N Kulkarni
Apr 1, 2016·Physiological Reviews·Michaela Kuhn
May 8, 2016·Journal of the American Society of Nephrology : JASN·Janina StaffelFrank Schweda
Jun 27, 2017·Translational Research : the Journal of Laboratory and Clinical Medicine·Alessandra GentiliCiriana Orabona
Sep 14, 2017·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·K VerbovenE E Blaak
May 18, 2018·Nature·Qiao Zhou, Douglas A Melton

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Citations

Dec 7, 2020·Thrombosis and Haemostasis·Dimitra AravaniStyliani Vakrou

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Methods Mentioned

BETA
PCR
dissection
FCS
transgenic
double

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