Study Title:

Insulin Treatment, High Blood Pressure, and Heart Failure

Study Abstract

Although many animal studies indicate insulin has cardioprotective effects, clinical studies suggest a link between insulin resistance (hyperinsulinemia) and heart failure (HF). Here we have demonstrated that excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents. Chronic pressure overload induced hepatic insulin resistance and plasma insulin level elevation. In contrast, cardiac insulin signaling was upregulated by chronic pressure overload because of mechanical stretch–induced activation of cardiomyocyte insulin receptors and upregulation of insulin receptor and Irs1 expression. Chronic pressure overload increased the mismatch between cardiomyocyte size and vascularity, thereby inducing myocardial hypoxia and cardiomyocyte death. Inhibition of hyperinsulinemia substantially improved pressure overload–induced cardiac dysfunction, improving myocardial hypoxia and decreasing cardiomyocyte death. Likewise, the cardiomyocyte-specific reduction of insulin receptor expression prevented cardiac ischemia and hypertrophy and attenuated systolic dysfunction due to pressure overload. Conversely, treatment of type 1 diabetic mice with insulin improved hyperglycemia during pressure overload, but increased myocardial ischemia and cardiomyocyte death, thereby inducing HF. Promoting angiogenesis restored the cardiac dysfunction induced by insulin treatment. We therefore suggest that the use of insulin to control hyperglycemia could be harmful in the setting of pressure overload and that modulation of insulin signaling is crucial for the treatment of HF.

From press release:

A team of researchers at Chiba University Graduate School of Medicine, Japan, has generated data in mice that suggest that using insulin to treat diabetes could be harmful if the patient has chronic high blood pressure.

Insulin is a hormone that controls the levels of glucose, a key source of energy, in our blood via its effects on the liver, muscle, and fat cells. How insulin affects the heart is not very clear, animal studies suggest that insulin protects the heart from stresses, whereas clinical studies suggest a link between high levels of insulin in the blood and heart failure.

The team, led by Issei Komuro, has generated data in mice indicating that while persistent high blood pressure induces liver cell resistance to insulin, it enhances insulin signaling in the heart. This excessive chronic insulin signaling exacerbated heart failure caused by high blood pressure. Importantly, although treating type 1 diabetic mice, which produce no insulin, with insulin stabilized their levels of glucose in the blood, it increased heart failure.

Together, these data lead the authors to suggest that insulin treatment could be harmful in the setting of chronic high blood pressure and that maintaining insulin signaling at normal levels is crucial for treating heart failure.

Study Information

1.Ippei Shimizu, Tohru Minamino, Haruhiro Toko, Sho Okada, Hiroyuki Ikeda, Noritaka Yasuda, Kaoru Tateno, Junji Moriya, Masataka Yokoyama, Aika Nojima, Gou Young Koh, Hiroshi Akazawa, Ichiro Shiojima, C. Ronald Kahn, E. Dale Abel and Issei Komuro
Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents.
Journal of Clinical Investigation
2010 April
Chiba University Graduate School of Medicine, Japan.

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