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Groundbreaking Antidiabetic Compound Unveiled: HPH-15 Reduces Blood Glucose Level and Combats Fat Accumulation

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, a top journal in the field of diabetes, 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.

Supported by Japan’s AMED Translational Research Program and other initiatives, this breakthrough showcases the innovative strides Kumamoto University is making in addressing global health challenges.
 
 
Image Title: HPH-15: A Promising New Treatment for Type 2 Diabetes
Image Caption: 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.

Reference
Authors
 		 Tsugumasa Toma, Nobukazu Miyakawa, Yuiichi Arakaki, Takuro Watanabe, Ryosei Nakahara, Taha F. S. Ali, Tanima Biswas, Mikio Todaka, Tatsuya Kondo, Mikako Fujita, Masami Otsuka, Eiichi Araki*, Hiroshi Tateishi*
Title of original paper
 		 An anti-fibrotic compound that ameliorates hyperglycaemia and fat accumulation in cell and HFD mouse models
Journal Diabetologia
DOI 10.1007/s00125-024-06260-y

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