Hyperamylinemia Increases IL-1{beta} Synthesis in the Heart via Peroxidative Sarcolemmal Injury

Hypersecretion of amylin is common in individuals with prediabetes, causes amylin deposition and proteotoxicity in pancreatic islets, and contributes to the development of type 2 diabetes. Recent studies also identified amylin deposits in failing hearts from patients with obesity or type 2 diabetes and demonstrated that hyperamylinemia accelerates the development of heart dysfunction in rats expressing human amylin in pancreatic β-cells (HIP rats). To further determine the impact of hyperamylinemia on cardiac myocytes, we investigated human myocardium, compared diabetic HIP rats with diabetic rats expressing endogenous (nonamyloidogenic) rat amylin, studied normal mice injected with aggregated human amylin, and developed in vitro cell models. We found that amylin deposition negatively affects cardiac myocytes by inducing sarcolemmal injury, generating reactive aldehydes, forming amylin-based adducts with reactive aldehydes, and increasing synthesis of the proinflammatory cytokine interleukin-1β (IL-1β) independently of hyperglycemia. These results are consistent with the pathological role of amylin deposition in the pancreas, uncover a novel contributing mechanism to cardiac myocyte injury in type 2 diabetes, and suggest a potentially treatable link of type 2 diabetes with diabetic heart disease. Although further studies are necessary, these data also suggest that IL-1β might function as a sensor of myocyte amylin uptake and a potential mediator of myocyte injury.

Diabetes Complications


Hyperamylinemia Increases IL-1{beta} Synthesis in the Heart via Peroxidative Sarcolemmal Injury was first posted on October 2, 2016 at 11:16 am.
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Reblogged 7 months ago from diabeticscareguide.com

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Amrita Wellness Medicine Clinic

Alina Porojan has been working as a natural medicine practitioner for the past twelve years, constantly educating herself and deepening her knowledge and clinical experience. Alina believes that health and healing is inherent to each of us, and sees her role as re-connecting us to our already existing potential for optimal health and wellness.