Advantage and Core Benefit
- Regulated Model
Our laboratory has characterized changed type 2 diabetes mellitus model, Otsuka Long-Evans Tokushima Fatty rats (OLETF) in their ventricular mechanical properties and myocardial metabolomes at the age of 25-30 weeks.
- Technical capabilities
Our laboratory has research performance in vivo hemodynamic experiments, 3-F catheter-tip micromanometer insertion into LV cavity.
Background and Technology
“Diabetic Cardiomyopathy” has been defined as diabetic heart failure in the absence of coronary atherosclerosis and hypertension in ACC/AHA and ESC guideline in 2013. Our researcher has brought findings and unraveled a mechanism that AMP deaminase3 (AMPD3) activity increased under the condition of pressure overloading and by miR-301b mediates upregulates expression of cardiac AMPD3 protein in the hearts of rat model of type 2 diabetes mellitus (OLETF). AMPD3 inhibition or suppression has a potential to lead to effective treatment and to breakthrough for Diabetic Cardiomyopathy.
We would like to propose the exploration of candidate compound of Diabetic Cardiomyopathy treatment by following step on a joint basis.
<First Step> High throughput screening by your chemical library
-in vitro assay
By using AMPD activity assay, we can screen chemicals which have potential for inhibiting AMPD.
AMPD activity in tissue extracts can be measured by detecting the amount of ammonia (NH3) derived from AMPD.
<Second Step> Analysis and narrowing the potential chemicals by screened chemicals
-in vivo screening
By using our OLETF rat, we can do demonstration and narrow of screened chemicals if those chemicals have a down-regulated AMPD activity in vivo.
Tatekoshi et al. Translational regulation by miR-301b upregulates AMP deaminase in diabetic hearts, J MOL CELL CARDIOL 119(2018) 138–146
H Kouzu et al. Excessive degradation of adenine nucleotides by up-regulated AMP deaminase underlies afterload-induced diastolic dysfunction in the type 2 diabetic heart, J MOL CELL CARDIOL 80(2015)136-145
Masaya Tanno et al. (Sapporo Medical University)
We are looking for partners, pharmaceutical or biotech companies to explore and co-develop candidate compounds for Diabetic Cardiomyopathy.