HPH-15 outperforms metformin by activating AMP-activated protein kinase (AMPK)

Saturday, December 21st, 2024

A research team at Kumamoto University, led by Visiting Associate Professor Hiroshi Tateishi and Professor Eiichi Araki, has identified HPH-15 as a promising alternative to existing diabetes 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.

Posted in Science | 2 Comments »

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Eric Brown says:

December 21, 2024 at 1:44 pm

In mice.
Adept says:

December 21, 2024 at 2:27 pm

HPH-15 may be more potent, but metformin also appears to operate via AMPK activation.

See, e.g.:

https://pubmed.ncbi.nlm.nih.gov/37782190/
“Metformin is a medication used to treat type 2 diabetes by inhibiting hepatic glucose production through adenosine monophosphate-activated protein kinase (AMPK) activation.”

https://pubmed.ncbi.nlm.nih.gov/31693892/
“Our results demonstrate that activation of AMPK by metformin improves mitochondrial respiration and hyperglycemia in obesity.”

https://pubmed.ncbi.nlm.nih.gov/33714781/
“Metformin is an oral antihyperglycemic drug widely used to treat type 2 diabetes mellitus (T2DM), acting via indirect activation of 5′ Adenosine monophosphate-activated Protein Kinase (AMPK).”

https://pubmed.ncbi.nlm.nih.gov/36435271/
“Since the antidiabetic effects of metformin are mostly mediated by the activation of AMPK. . .”

A more potent AMPK activator might be useful, but there’s surely a lot of other stuff going on — secondary targets, pharmacokinetic considerations, etc.

Some other research chemicals are highly specific and potent AMPK activators. Whether or not they’re useful in diabetes, though, appears to still be an open question. One of them, AICAR, has seen some use as an athletic doping agent. Anyway, there’s an interesting review here: https://www.nature.com/articles/emm201616

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HPH-15 outperforms metformin by activating AMP-activated protein kinase (AMPK)

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