{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:34:56Z","timestamp":1790836496395,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,21]],"date-time":"2023-01-21T00:00:00Z","timestamp":1674259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Diabetes Research Action and Education Foundation (USA)"},{"name":"Virginia Tech Library Subvention Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The prevalence of type 2 diabetes (T2D) has been rising dramatically in many countries around the world. The main signatures of T2D are insulin resistance and dysfunction of \u03b2-cells. While there are several pharmaceutical therapies for T2D, no effective treatment is available for reversing the functional decline of pancreatic \u03b2-cells in T2D patients. It has been well recognized that glucagon-like peptide-1 (GLP-1), which is an incretin hormone secreted from intestinal L-cells, plays a vital role in regulating glycemic homeostasis via potentiating glucose-stimulated insulin secretion and promoting \u03b2-cell function. We found that genipin, a natural compound from Elli, can directly target intestinal L-cells, leading to the secretion of GLP-1. Incubation of the cells with genipin elicited a rapid increase in intracellular Ca2+. Inhibition of PLC ablated genipin-stimulated Ca2+ increase and GLP-1 secretion, suggesting that genipin-induced GLP-1 release from cells is dependent on the PLC\/Ca2+ pathway. In vivo, acute administration of genipin stimulated GLP-1 secretion in mice. Chronically, treatment with genipin via oral gavage at 50 mg\/kg\/day for 6 weeks reversed hyperglycemia and insulin resistance in high-fat-diet (HFD)-induced obese mice. Moreover, genipin alleviated the impaired lipid metabolism and decreased lipid accumulation in the liver of obese mice. These results suggest that naturally occurring genipin might potentially be a novel agent for the treatment of T2D and diet-induced fatty liver disease.<\/jats:p>","DOI":"10.3390\/ijms24032131","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T02:27:45Z","timestamp":1674440865000},"page":"2131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Identification of Genipin as a Potential Treatment for Type 2 Diabetes"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0022-865X","authenticated-orcid":false,"given":"Yajun","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Human Nutrition, Foods, and Exercise, College of Agricultural and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9631-8309","authenticated-orcid":false,"given":"Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Foods, and Exercise, College of Agricultural and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3877-8198","authenticated-orcid":false,"given":"Dongmin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Foods, and Exercise, College of Agricultural and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,21]]},"reference":[{"key":"ref_1","unstructured":"Centers for Disease Control and Prevention (2023, January 12). 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