AMP-activated protein kinase (AMPK) is a protein that detects intracellular energy deficiency in the liver, muscle, and adipose tissue and is activated by metabolic stresses such as caloric restriction and exercise. AMPK activation induces glucose metabolization through the same mechanism as in exercise with no burden on the pancreas, making it a promising target for developing drugs for the treatment of type 2 diabetes.
A research group led by Visiting Associate Professor Hiroshi Tateishi (Chief, Research and Development Headquarters, Hirata Corporation) and Graduate Student Tsugumasa Toma of the Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences (Pharmaceutical Sciences) at Kumamoto University, and Professor Emeritus Eiichi Araki of the Department of Diabetes, Metabolism, and Endocrinology at Kumamoto University Hospital, has discovered that histidine-pyridine-histidine ligand derivative (HPH-15), a low-molecular-weight compound being developed as an antifibrotic agent, has lipid metabolism improving effects in addition to glucose-lowering effects via AMPK activation.
Since excessive fat accumulation in tissues is a risk factor for diabetic complications, HPH-15, effective in reducing fat and blood glucose levels, is expected to be useful as a novel therapeutic agent for type 2 diabetes. In patients with type 2 diabetes, tissue fibrosis is also accelerated, resulting in severe symptoms such as organ failure. HPH-15 differs from the conventional drug metformin in that it also has antifibrotic effects on the liver and adipose tissue and holds the promise of being useful for liver complications, including cirrhosis and NAFLD/NASH associated with diabetes. The study was published in Diabetologia.
Journal Information
Publication: Diabetologia
Title: An antifibrotic compound that ameliorates hyperglycaemia and fat accumulation in cell and HFD mouse models
DOI: 10.1007/s00125-024-06260-y
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