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In Wistar rats, 10 weeks of PHG treatment did not prevent HFD-induced weight gain but significantly mitigated fasting hyperglycemia, impaired insulin responses, and liver steatosis. This protective effect was not linked to hepatic lipogenesis or AMP-activated protein kinase (AMPK) activation. Instead, PHG improved mitochondrial function by reducing oxidative stress, enhancing ATP production, and increasing anti-oxidant enzyme activity. PHG also relaxed gastric smooth muscles via potassium channel activation and nitric oxide (NO) signaling, potentially delaying gastric emptying. A pilot intervention in pre-diabetic men confirmed PHG\u2019s efficacy in improving postprandial glycemic control and altering lipid metabolism. These findings suggest PHG as a potential therapeutic for NAFLD and insulin resistance, acting through mechanisms involving mitochondrial protection, anti-oxidant activity, and gastric motility modulation. Further clinical evaluation is warranted to explore PHG\u2019s full therapeutic potential.<\/jats:p>","DOI":"10.3390\/ijms251910291","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T04:01:24Z","timestamp":1727236884000},"page":"10291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["New Application of an Old Drug: Anti-Diabetic Properties of Phloroglucinol"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0645-7020","authenticated-orcid":false,"given":"Krzysztof","family":"Drygalski","sequence":"first","affiliation":[{"name":"Department of Hypertension and Diabetology, Medical University of Gdansk, 80-214 Gdansk, 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