Hyperamylinemia increases IL-1β synthesis in the heart via peroxidative sarcolemmal injury

Miao Liu, Nirmal Verma, Xiaoli Peng, Sarah Srodulski, Andrew Morris, Martin Chow, Louis B. Hersh, Jing Chen, Haining Zhu, Mihai G. Netea, Kenneth B. Margulies, Sanda Despa, Florin Despa

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2772-2783
Number of pages12
JournalDiabetes
Volume65
Issue number9
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

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    Liu, M., Verma, N., Peng, X., Srodulski, S., Morris, A., Chow, M., Hersh, L. B., Chen, J., Zhu, H., Netea, M. G., Margulies, K. B., Despa, S., & Despa, F. (2016). Hyperamylinemia increases IL-1β synthesis in the heart via peroxidative sarcolemmal injury. Diabetes, 65(9), 2772-2783. https://doi.org/10.2337/db16-0044