Hyperamylinemia Increases IL-1ß Synthesis in the Heart via Peroxidative
Sarcolemmal Injury.
Authors Liu M, Verma N, Peng X, Srodulski S, Morris A, Chow M, Hersh LB, Chen J, Zhu H,
Netea MG, Margulies KB, Despa S, Despa F
Submitted By Florin Despa on 8/1/2016
Status Published
Journal Diabetes
Year 2016
Date Published 6/1/2016
Volume : Pages Not Specified : Not Specified
PubMed Reference 27335231
Abstract Hypersecretion of amylin is common in individuals with pre-diabetes, causes
amylin deposition and proteotoxicity in pancreatic islets and contributes to the
development of type-2 diabetes. Recent studies identified amylin deposits also
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 ß-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
(non-amyloidogenic) 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 pro-inflammatory cytokine interleukin (IL)-1ß
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.
While further studies are necessary, these data also suggest that IL-1ß might
function as a sensor of myocyte amylin uptake and potential mediator of myocyte
injury.

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