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The endocrine heart - metabolic actions of atrial natriuretic peptide

Jujic, Amra LU (2015) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2015:136.
Abstract
Abstract

The natriuretic peptides (NPs), namely atrial natriuretic peptide (ANP) and bran natriuretic peptide (BNP), which are secreted from cardiomyocytes in response to cardiac wall stress, play a significant role in the regulation of blood pressure, intravascular volume, and cardiac remodeling. Recently, NPs emerged as hormones with metabolic actions such as inhibition of the renin-angiotensin system and inhibition of inflammation, together with lipolysis and adipose tissue browning. Further, cross-sectional studies showed that NPs are reduced in subjects with obesity and insulin resistance, proposing a role of NPs in metabolic disease such as diabetes.

In paper I, a prospective study examining the relationship... (More)
Abstract

The natriuretic peptides (NPs), namely atrial natriuretic peptide (ANP) and bran natriuretic peptide (BNP), which are secreted from cardiomyocytes in response to cardiac wall stress, play a significant role in the regulation of blood pressure, intravascular volume, and cardiac remodeling. Recently, NPs emerged as hormones with metabolic actions such as inhibition of the renin-angiotensin system and inhibition of inflammation, together with lipolysis and adipose tissue browning. Further, cross-sectional studies showed that NPs are reduced in subjects with obesity and insulin resistance, proposing a role of NPs in metabolic disease such as diabetes.

In paper I, a prospective study examining the relationship between baseline levels of atrial ANP and BNP, and incident diabetes, we showed that low baseline levels of ANP, but not BNP, predict development of diabetes at follow up 16 years later, in a model adjusted for clinical diabetes risk factors. The individuals in the lowest quartiles of ANP were at greatest risk of developing diabetes at follow-up.

In paper II, we sought to explore whether the above-mentioned association is causal by exploring the association between a common genetic variant, rs5068 (previously shown to be associated with higher levels of ANP), and incident diabetes at follow up 14 years later. The study showed that carriers of at least on copy of the G allele of rs5068 had lower likelihood of incident diabetes within 14 years.

Since earlier studies demonstrated that ANP inhibits fibroblast growth and slows down proliferative remodeling of the myocardium, paper III aimed to assess the prevalence of left ventricular hypertrophy in a population free from diabetes, by genotype of rs5068. The study demonstrated that the minor allele of rs5068, (previously shown to be associated with higher levels of ANP), was associated with lower prevalence of left ventricular hypertrophy and lower left ventricular mass.

Finally, in paper IV, we studied possible mechanistic explanations of ANPs beneficial role in diabetes development. The study demonstrated prospectively that low ANP levels at baseline were associated with higher risk of insulin resistance at follow up 16 years later, which might serve as a mechanistic explanation for the diabetes development, since insulin resistance often precedes diabetes. Further, this study demonstrated that increase in ANP levels was associated with increase in glucose dependent insulinotropic peptide (GIP) post glucose challenge secretion. Since GIP acts as a blood glucose stabilizer, it is possible that ANP’s beneficial effects on diabetes development are incretin dependent. (Less)
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author
supervisor
opponent
  • Associate professor Söderberg, Stefan, Umeå University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Atrial natriuretic peptide, type 2 diabetes, rs5068, insulin resistance, glucose dependent insulinotropic peptide, glucagon-like peptide-1, left ventricular hypertrophy
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2015:136
pages
78 pages
publisher
Hypertension and Cardiovascular Disease
defense location
CRC 2, (CRC 93-09-002a) Jan Waldenströms gata 35, SUS Malmö
defense date
2015-12-17 09:00
ISSN
1652-8220
ISBN
978-91-7619-216-0
language
English
LU publication?
yes
id
41dc7427-4b95-4c0b-a497-69fb5bac6c17 (old id 8228440)
date added to LUP
2015-11-26 09:32:42
date last changed
2016-09-19 08:44:47
@phdthesis{41dc7427-4b95-4c0b-a497-69fb5bac6c17,
  abstract     = {Abstract<br/><br>
The natriuretic peptides (NPs), namely atrial natriuretic peptide (ANP) and bran natriuretic peptide (BNP), which are secreted from cardiomyocytes in response to cardiac wall stress, play a significant role in the regulation of blood pressure, intravascular volume, and cardiac remodeling. Recently, NPs emerged as hormones with metabolic actions such as inhibition of the renin-angiotensin system and inhibition of inflammation, together with lipolysis and adipose tissue browning. Further, cross-sectional studies showed that NPs are reduced in subjects with obesity and insulin resistance, proposing a role of NPs in metabolic disease such as diabetes. <br/><br>
In paper I, a prospective study examining the relationship between baseline levels of atrial ANP and BNP, and incident diabetes, we showed that low baseline levels of ANP, but not BNP, predict development of diabetes at follow up 16 years later, in a model adjusted for clinical diabetes risk factors. The individuals in the lowest quartiles of ANP were at greatest risk of developing diabetes at follow-up. <br/><br>
In paper II, we sought to explore whether the above-mentioned association is causal by exploring the association between a common genetic variant, rs5068 (previously shown to be associated with higher levels of ANP), and incident diabetes at follow up 14 years later. The study showed that carriers of at least on copy of the G allele of rs5068 had lower likelihood of incident diabetes within 14 years.<br/><br>
Since earlier studies demonstrated that ANP inhibits fibroblast growth and slows down proliferative remodeling of the myocardium, paper III aimed to assess the prevalence of left ventricular hypertrophy in a population free from diabetes, by genotype of rs5068. The study demonstrated that the minor allele of rs5068, (previously shown to be associated with higher levels of ANP), was associated with lower prevalence of left ventricular hypertrophy and lower left ventricular mass.<br/><br>
Finally, in paper IV, we studied possible mechanistic explanations of ANPs beneficial role in diabetes development. The study demonstrated prospectively that low ANP levels at baseline were associated with higher risk of insulin resistance at follow up 16 years later, which might serve as a mechanistic explanation for the diabetes development, since insulin resistance often precedes diabetes. Further, this study demonstrated that increase in ANP levels was associated with increase in glucose dependent insulinotropic peptide (GIP) post glucose challenge secretion. Since GIP acts as a blood glucose stabilizer, it is possible that ANP’s beneficial effects on diabetes development are incretin dependent.},
  author       = {Jujic, Amra},
  isbn         = {978-91-7619-216-0},
  issn         = {1652-8220},
  keyword      = {Atrial natriuretic peptide,type 2 diabetes,rs5068,insulin resistance,glucose dependent insulinotropic peptide,glucagon-like peptide-1,left ventricular hypertrophy},
  language     = {eng},
  pages        = {78},
  publisher    = {Hypertension and Cardiovascular Disease},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {The endocrine heart - metabolic actions of atrial natriuretic peptide},
  volume       = {2015:136},
  year         = {2015},
}