What do high serum glucose levels mean

Cardially secreted CTRP9: Cellular signaling mechanisms, importance for myocardial remodeling, systemic insulin resistance and possible gene therapy approaches.

Applicant Professor Dr. Jörg Heineke
Heidelberg University
Mannheim Medical Faculty
European Center for Angioscience (ECAS)
Professor Dr. Oliver J. Muller
University Medical Center Schleswig-Holstein
Campus Kiel
Clinic for Cardiology, Angiology and Internal Intensive Care Medicine
Subject area cardiology, angiology
Funding Funding from 2013 to 2019
German Research Foundation (DFG) - project number 234125093
Chronic heart failure is a common disease with a high mortality rate. Epidemiological data confirm the increasing incidence of diabetes mellitus with insulin resistance in patients with heart failure. On the one hand, diabetes can lead to the development of cardiomypathy, but on the other hand, heart failure also seems to favor the development of diabetes with insulin resistance. It is assumed, among other things, that factors secreted endocrinically into the blood by the myocardium can influence the peripheral metabolic activity (e.g. in skeletal muscle) and thus also the insulin resistance. In the search for cardiac secreted factors, we identified the adiponectin-related glycoprotein CTRP9, which is mainly expressed in the myocardium and is also released into the blood. Interestingly, systemic overexpression of CTRP9 can lower serum glucose levels. We found CTRP9 particularly upregulated in the compensated hypertrophy, but not in the insufficient myocardium. Our preliminary data suggest a potent cardiomyocytic growth (hypertrophy) inhibiting effect of CTRP9. Cardiac hypertrophy occurs both in the context of diabetic cardiomyopathy and in systemic arterial hypertension and is considered a preliminary stage of heart failure. We therefore postulate that cardially secreted CTRP9 can on the one hand improve peripheral insulin resistance and on the other hand prevent cardiac insufficiency locally in the myocardium by inhibiting hypertrophy. In the context of this application we want to find receptors, cellular signaling mechanisms, transcription factors and target genes of CTRP9 in cardiomyocytes, skeletal muscle, fat and liver cells. Furthermore, we want to test in CTRP9 knock-out mice and through gene therapy cardiac overexpression of CTRP9 whether it has an influence on insulin resistance and the myocardial remodeling processes in the development of heart failure after cardiac stress or diabetic metabolism.
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