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UC Davis researchers discover a biological link between diabetes and heart disease
Date:9/30/2013

cientists have known for a while that CaMKII plays a critical role in normal cardiac function, ours is the first study to identify O-GlcNAc as a direct activator of CaMKII with hyperglycemia," said Bers.

The research encompassed detailed molecular experiments in rat and human proteins and tissues, calcium imaging in isolated rat cardiac myocytes exposed to high glucose, and assessments of whole heart arrhythmias with optical mapping in isolated hearts and in live diabetic rats. This comprehensive approach allowed Bers and his team to identify the specific site of sugar attachment to CaMKII, along with how that attachment activated CaMKII and caused calcium-dependent arrhythmias.

"Since O-GlcNAc is directly made from glucose and serves as a major nutrient sensor in regulating most cellular processes, it is perhaps not surprising that attachment of this sugar to proteins is emerging as a major molecular mechanism of glucose toxicity in diabetes," said Gerald Hart, DeLamar Professor and director of biological chemistry at Johns Hopkins University School of Medicine, and one of Bers' collaborators.

"However, this represents the most clear-cut mechanistic study to date of how high glucose can directly affect the function of a critical regulatory protein," said Hart. "The Bers group's findings undoubtedly will lead to development of treatments for diabetic cardiovascular disease and, potentially, therapeutics for glucose toxicity in other tissues that are affected by diabetes such as the retina, the nervous system and the kidney."

In an additional experiment, the team found elevated levels of O-GlcNAc-modified CaMKII in both hearts and brains of deceased humans who were diagnosed with diabetes, with the highest levels in the hearts of patients who had both heart failure and diabetes.

"Our discovery is likely to have ripple effects in many other fields," said Bers. "One key next step will be to determine if the fusion of
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Contact: Karen Finney
karen.finney@ucdmc.ucdavis.edu
916-734-9064
University of California - Davis Health System
Source:Eurekalert

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