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Diabetologia
Published in: Diabetologia 9/2014

01-09-2014 | Article

Independent effects of circulating glucose, insulin and NEFA on cardiac triacylglycerol accumulation and myocardial insulin resistance in a swine model

Authors: Maria Angela Guzzardi, Leanne Hodson, Letizia Guiducci, Elena Sanguinetti, Pietro Di Cecco, Tiziana Liistro, Cristina Vassalle, Silvia Pardini, Lucia Giorgetti, Piero A. Salvadori, Silvia Burchielli, Patricia Iozzo

Published in: Diabetologia | Issue 9/2014

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Abstract

Aims/hypothesis

Cardiac steatosis and myocardial insulin resistance elevate the risk of cardiac complications in obesity and diabetes. We aimed to disentangle the effects of circulating glucose, insulin and NEFA on myocardial triacylglycerol (TG) content and myocardial glucose uptake.

Methods

Twenty-two pigs were stratified according to four protocols: low NEFA + low insulin (nicotinic acid), high NEFA + low insulin (fasting) and high insulin + low NEFA ± high glucose (hyperinsulinaemia–hyperglycaemia or hyperinsulinaemia–euglycaemia). Positron emission tomography, [U-13C]palmitate enrichment techniques and tissue biopsies were used to assess myocardial metabolism. Heart rate and rate–pressure product (RPP) were monitored.

Results

Myocardial glucose extraction was increased by NEFA suppression and was similar in the hyperinsulinaemia–hypergylcaemia, hyperinsulinaemia–euglycaemia and nicotinic acid groups. Hyperglycaemia enhanced myocardial glucose uptake due to a mass action. Myocardial TG content was greatest in the fasting group, whereas hyperinsulinaemia had a mild effect. Heart rate and RPP increased in hyperinsulinaemia–euglycaemia, in which cardiac glycogen content was reduced. Heart rate correlated with myocardial TG and glycogen content.

Conclusions/interpretation

Elevated NEFA levels represent a powerful, self-sufficient promoter of cardiac TG accumulation and are a downregulator of myocardial glucose uptake, indicating that the focus of treatment should be to ‘normalise’ adipose tissue function to lower the risk of cardiac TG accumulation and myocardial insulin resistance. The observation that hyperinsulinaemia and nicotinic acid led to myocardial fuel deprivation provides a potential explanation for the cardiovascular outcomes reported in recent intensive glucose-lowering and NEFA-lowering clinical trials.
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Metadata
Title
Independent effects of circulating glucose, insulin and NEFA on cardiac triacylglycerol accumulation and myocardial insulin resistance in a swine model
Authors
Maria Angela Guzzardi
Leanne Hodson
Letizia Guiducci
Elena Sanguinetti
Pietro Di Cecco
Tiziana Liistro
Cristina Vassalle
Silvia Pardini
Lucia Giorgetti
Piero A. Salvadori
Silvia Burchielli
Patricia Iozzo
Publication date
01-09-2014
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 9/2014
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-014-3307-8

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