Prevalence of diabetes, especially type 2 diabetes mellitus (T2DM) is increasing worldwide. Millions of people are already affected by T2DM and estimates predict over half a billion people will likely be suffering from the disease by 2030. T2DM is associated with an increased risk of developing cardiovascular disease. Cardiovascular dysfunction is the leading cause of mortality among type 2 diabetics. Treatment for T2DM has changed over time. Though it was once known as insulin independent, a large portion of type 2 diabetics are now treated with insulin injections. However, type 2 diabetics treated with insulin are more likely to suffer from heart complications. Due to this, we sought to determine the specific effect of insulin and insulin-induced ceramide accrual on heart mitochondrial bioenergetics. To do so we used both in vitro and in vivo models. H9c2 cardiomyocytes and adult male mice were treated with insulin with or without the ceramide biosynthesis inhibitor myriocin. Mitochondrial bioenergetics were determined in permeabilized cardiomyocytes and myocardium. In this study we demonstrate that insulin induced ceramide accrual in both isolated cardiomyocytes and whole murine myocardium. We further found that insulin treatment is sufficient to disrupt mitochondrial respiration in both models. Inhibition of the ceramide accrual rescued mitochondrial respiration, indicating that ceramide is necessary for the insulin-induced alterations in heart mitochondrial respiration. These results suggest that insulin has a role in the development of heart complications associated with T2DM due to cardiomyocyte mitochondrial disruption. They also implicate ceramide as a possible mediator in the development of insulin-related heart disorders.
College and Department
Life Sciences; Physiology and Developmental Biology
BYU ScholarsArchive Citation
Hodson, Aimee Elizabeth, "Insulin Treatment Increases Myocardial Ceramide Accumulation and Disrupts Cardiometabolic Function" (2016). Theses and Dissertations. 5954.
type 2 diabetes, ceramide, mitochondria, hyperinsulinemia, insulin