Insulin treatment increases myocardial ceramide accumulation and disrupts cardiometabolic function

Cardiovascular Diabetology

Benjamin T. Bikman¹  Trevor S. Tippetts¹  Aimee E. Hodson¹ 

[1] Department of Physiology and Developmental Biology, Brigham Young University, 3017 LSB, Provo 84602, UT, USA

关键词: Ceramide;    Mitochondria;    Hyperinsulinemia;    Insulin;   

Others  :  1235003
DOI  :  10.1186/s12933-015-0316-y

 received in 2015-09-15, accepted in 2015-12-12,  发布年份 2015

【 摘 要 】

Background

States of hyperinsulinemia, particularly insulin resistance and type 2 diabetes mellitus, are becoming remarkably common, with roughly half a billion people likely to suffer from the disorder within the next 15 years. Along with this rise has been an associated increased burden of cardiovascular disease. Considering type 2 diabetics treated with insulin are more likely to suffer from heart complications, we sought to determine the specific effect of insulin on ceramide-dependent cardiometabolic risk factors, including insulin resistance and altered heart mitochondrial physiology.

Methods

H9c2 cardiomyocytes and adult mice were treated with insulin with or without myriocin to inhibit ceramide biosynthesis. Insulin and glucose changes were tracked throughout the study and mitochondrial bioenergetics was determined in permeabilized cardiomyocytes and myocardium.

Results

Herein, we demonstrate that insulin is sufficient to disrupt heart mitochondrial respiration in both isolated cardiomyocytes and whole myocardium, possibly by increasing mitochondrial fission. Further, insulin increases ceramide accrual in a time-dependent manner, which is necessary for insulin-induced alterations in heart mitochondrial respiration and insulin resistance.

Conclusions

Collectively, these observations have two implications. First, they indicate a pathological role of insulin in heart complications stemming from mitochondrial disruption. Second, they identify ceramide as a possible mediator of insulin-related heart disorders.

【 授权许可】

   
2015 Hodson et al.

【 图 表 】

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