by Kumamoto University

HPH-15 offers multiple benefits for managing type 2 diabetes, including effective blood glucose control, reduced risk of lactic acidosis, improved insulin resistance, and suppression of fat buildup and fibrosis in the liver and fat tissue, with these effects observed in studies using muscle, liver, and fat tissue models. These properties make HPH-15 a potentially more effective treatment for type 2 diabetes. Credit: Hiroshi Tateishi, Eiichi Araki, Kumamoto University

Kumamoto University scientists have unveiled a novel compound, HPH-15, with dual effects of reducing blood glucose levels and combating fat accumulation, marking a significant leap in diabetes treatment innovation.

Type 2 diabetes, a condition affecting millions worldwide, is often accompanied by complications like fatty liver and insulin resistance, which challenge current treatment methods. The research team, led by Visiting Associate Professor Hiroshi Tateishi and Professor Eiichi Araki, has identified HPH-15 as a promising alternative to existing medications like metformin.

The study, published in Diabetologia, demonstrates that HPH-15 outperforms metformin by activating AMP-activated protein kinase (AMPK)—a critical protein regulating energy balance—at lower doses.

HPH-15 not only improved glucose uptake in liver, muscle, and fat cells but also significantly reduced fat accumulation in high-fat diet (HFD)-induced obese mice. Unlike metformin, HPH-15 exhibited additional antifibrotic properties, potentially addressing liver fibrosis and other complications often seen in diabetes patients.

Key findings include:

• Enhanced Efficacy: HPH-15 activated AMPK and promoted glucose uptake at concentrations 200 times lower than metformin.

• Fat Reduction: The compound decreased subcutaneous fat by 44% and mitigated fatty liver more effectively than metformin in preclinical trials.

• Safety Profile: Lactic acid production, a concern with metformin, was either comparable or lower with HPH-15, suggesting reduced risks of lactic acidosis.

These results suggest that HPH-15 could redefine diabetes management by combining glucose control with the prevention of obesity-related complications. "This compound holds transformative potential for diabetes treatment, offering benefits beyond blood sugar regulation," said Professor Mikako Fujita from the Faculty of Life Sciences at Kumamoto University.

More information: Tsugumasa Toma et al, An antifibrotic compound that ameliorates hyperglycaemia and fat accumulation in cell and HFD mouse models, Diabetologia (2024). DOI: 10.1007/s00125-024-06260-y

Journal information: Diabetologia 

Provided by Kumamoto University