Amylin and diabetic cardiomyopathy - amylin-induced sarcolemmal Ca(2+) leak is
independent of diabetic remodeling of myocardium.
Authors Liu M, Hoskins A, Verma N, Bers DM, Despa S, Despa F
Submitted By Florin Despa on 11/8/2017
Status Published
Journal Biochimica et biophysica acta
Year 2017
Date Published 10/1/2017
Volume : Pages Not Specified : Not Specified
PubMed Reference 29066284
Abstract Amylin is a pancreatic ß-cell hormone co-secreted with insulin, plays a role in
normal glucose homeostasis, and forms amyloid in the pancreatic islets of
individuals with type-2 diabetes. Aggregated amylin is also found in blood and
extra-pancreatic tissues, including myocardium. Myocardial amylin accumulation
is associated with myocyte Ca(2+) dysregulation in diabetic rats expressing
human amylin. Whether deposition of amylin in the heart is a consequence of or a
contributor to diabetic cardiomyopathy remains unknown. We used amylin knockout
(AKO) mice intravenously infused with either human amylin (i.e, the aggregated
form) or non-amyloidogenic (i.e., monomeric) rodent amylin to test the
hypothesis that aggregated amylin accumulates in the heart in the absence of
diabetes. AKO mice infused with human amylin, but not rodent amylin, showed
amylin deposits in the myocardium. Cardiac amylin level was larger in males
compared to females. Sarcolemmal Ca(2+) leak and Ca(2+) transients were
increased in myocytes isolated from males infused with human amylin while no
significant changes occurred in either females injected with human amylin or in
rat amylin-infused mice. In isolated cardiac myocytes, the amylin receptor
antagonist AC-187 did not effectively block the interaction of amylin with the
sarcolemma. In conclusion, circulating aggregated amylin accumulates
preferentially in male vs. female hearts and its effects on myocyte Ca(2+)
cycling do not require diabetic remodeling of the myocardium. This article is
part of a Special Issue entitled: Cardiac Adaptations to Obesity, Diabetes and
Insulin Resistance: Novel Targets and Therapies, edited by Dr. Jan Glatz,
Professor Jason Dyck and Dr. Christine Des Rosiers.

Complications