[National University Corporation Kumamoto University] Discovery of a new therapeutic drug candidate that improves type 2 diabetes and associated fat accumulation and fibrosis
*National University Corporation Kumamoto University*
Press release: September 11, 2024
**
Discovery of new therapeutic drug candidates that improve type 2 diabetes and associated fat accumulation and fibrosis
[Point]
We discovered that HPH-15, which was developed as an anti-fibrotic drug in our laboratory, is a candidate drug for the treatment of type 2 diabetes.
Experiments using model cells of organs involved in glucose metabolism revealed that HPH-15 has the effect of activating AMPK, a protein important for improving glucose metabolism.
Experiments using high-fat-fed obesity model mice showed that HPH-15 suppresses blood sugar levels and has stronger fat accumulation suppressing and antifibrotic effects in the liver and adipose tissue than the same drug metformin. I made it clear.
HPH-15 is expected to be developed as a revolutionary drug that has both blood sugar level and fat reducing effects as well as
anti-fibrotic effects.
[Summary explanation]
AMPK is a protein that senses intracellular energy shortages in the liver, muscle, and adipose tissue, and is activated by calorie restriction and exercise. Therefore, activation of AMPK metabolizes sugar by the same mechanism as during exercise and does not put a burden on the pancreas, making it a promising target for drug discovery for type 2 diabetes treatment.
This time, visiting associate professor at Tateishi University, Kumamoto University Graduate School of Life Sciences (Pharmaceutical Sciences) Science Farm Biofunctional Chemistry Collaborative Research Course (Hirata Kiko Co., Ltd. Research and Development Headquarters) Genetic Resources Research and Development Department, Research and Development Group, Chief), Tsugumasa Tomasa, 3rd year doctoral student; Graduate student, Eiichi Araki, Department of Diabetes, Metabolism, and Endocrinology, Kumamoto University Hospital. Professor Emeritus (Advisor, Kikuchi-gun City Medical Association Hospital, Health and Sports Education Research Center, Kumamoto Health Science University)
The research group led by Project Professor (Specially Appointed Professor) et al. has discovered that HPH-15, a low-molecular-weight compound currently under development as an anti-fibrotic*1 drug, has a lipid metabolism-improving effect in addition to a hypoglycemic effect through activation of AMPK. I made it clear that there is. Since fat accumulation is a risk factor for complications, HPH-15, which has both the effect of reducing fat and blood sugar levels, is expected to become a breakthrough drug.
The results of this research were published online in Diabetologia, a top European scientific journal related to diabetes, on September 9, 2020. This research is supported by the Japan Society for the Promotion of Science Research Fellowship, Grants-in-Aid for Scientific Research, Translational Research Program of the Japan Agency for Medical Research and Development (AMED), Higo Bank Innovation Support Program, and next-generation venture creation support
commercialization feasibility study. This project was carried out with the support of a commissioned project.
[Development]
This study revealed that HPH-15 not only has a hypoglycemic effect through AMPK activation, but also suppresses fat accumulation and adipose tissue hypertrophy. Since excessive fat accumulation in tissues is a risk factor for diabetic complications, HPH-15, which has both fat and blood sugar level reducing effects, is expected to be useful as a new type 2 diabetes treatment. It is also known that tissue fibrosis is accelerated in patients with type 2 diabetes, leading to serious symptoms such as organ failure. HPH-15 differs from metformin in that it also has anti-fibrotic effects on the liver and adipose tissue, and is expected to be a useful drug for liver complications such as cirrhosis associated with diabetes and NAFLD/NASH*5.
[Term explanation]
*1: Fibrosis
A phenomenon in which extracellular matrix such as collagen is deposited excessively in the skin and tissues, causing them to harden. As tissue fibrosis progresses, the original functions of the tissue are impaired.
[Paper information]
Paper title: An anti-fibrotic compound that ameliorates hyperglycaemia and fat accumulation in cells and HFD mouse models.
Authors: Masa Tomasa1, Nobukazu Miyagawa2, Yui Aragaki1, Takuro Watanabe2, Ryoharu Nakahara1, Taha F.S. Ali1,3, Tanima
Biswas1, Mikio Todaka4, Tatsuya Kondo2, Mikako Fujita1, Masami Otsuka1,5, Eiichi Araki2,6,7*, Dai Tateishi1,8* (*Corresponding authors)
1Kumamoto University Graduate School of Life Sciences (Pharmaceutical Sciences) Science Farm Biofunctional Chemistry Collaborative Research Course, 2Kumamoto University Hospital Department of Diabetes, Metabolism, and Endocrinology, 3Minia University Faculty of
Pharmaceutical Sciences, Department of Medicinal Chemistry, 4Todaka Internal Medicine Clinic, 5Science Farm Co., Ltd. Research and Development Headquarters, 6Kikuchi-gun City Medical Association Hospital, 7Kumamoto Health Science University Health and Sports Education Research Center, 8Hirata
Corporation, Research and Development Headquarters, Research and Development Department
Magazine: Diabetologia
doi: 10.1007/s00125-024-06260-y
URL: https://link.springer.com/article/10.1007/s00125-024-06260-y
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