{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:33:18Z","timestamp":1789468398980,"version":"build-2803163510"},"reference-count":176,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Young Qi-Huang Scholars Training Program of the State Administration of Traditional Chinese Medicine"},{"name":"Yunnan Xingdian Talent Plan Innovation Team Project","award":["202505AS350014"],"award-info":[{"award-number":["202505AS350014"]}]},{"name":"Yunnan Provincial Major Science and Technology Special Project","award":["202302AA310014"],"award-info":[{"award-number":["202302AA310014"]}]},{"name":"Yunnan Provincial Key Research and Development Program","award":["202503AP140023"],"award-info":[{"award-number":["202503AP140023"]}]},{"name":"Yunnan Science and Technology Talent and Platform Program","award":["202105AG070012"],"award-info":[{"award-number":["202105AG070012"]}]},{"name":"Open Project of Yunnan Key Laboratory of Southern Medicinal Utilization","award":["202105AG070012XS2608"],"award-info":[{"award-number":["202105AG070012XS2608"]}]},{"name":"Open Project of Yunnan Key Laboratory of Southern Medicinal Utilization","award":["202105AG070012XS2635"],"award-info":[{"award-number":["202105AG070012XS2635"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM) is a major global health challenge, with insulin resistance (IR) and islet dysfunction as its core pathophysiology. Current glucose-lowering agents, including insulin secretagogues, insulin sensitizers, DPP\u2013IV inhibitors, SGLT-2 inhibitors, and GLP-1 receptor agonists, effectively control blood glucose and may partly improve \u03b2-cell function indirectly, but they do not directly target the functional defects of pancreatic \u03b2 cells. Developing drugs that precisely modulate islet function is therefore a key direction. Natural products, with their structural diversity, established glucose-lowering activity, and derivation from medicinal plants with long clinical use, have become an important source of lead compounds for drugs targeting these mechanisms. The main pathways through which natural products act include: (1) promoting insulin secretion through direct and indirect secretagogue mechanisms (modulating ion channels, metabolic enzymes, incretin signaling); (2) preserving \u03b2-cell function and mass by maintaining the differentiated phenotype, promoting regeneration, alleviating oxidative stress, inhibiting apoptosis and pyroptosis, attenuating inflammation, and suppressing hIAPP toxic aggregation and endoplasmic reticulum stress; and (3) other pathways with incompletely elucidated mechanisms that also contribute to islet protection. This article delineates these molecular mechanisms and highlights the limited ability of current agents to directly restore and protect \u03b2-cell function. It provides a theoretical basis for developing novel drugs that integrate glycemic control with islet restoration based on natural lead compounds, and offers a framework for further mechanistic studies. In addition, it encourages the exploration of unidentified active constituents and unique pathways, while also addressing challenges such as target identification and structure\u2013activity relationships.<\/jats:p>","DOI":"10.3390\/biom16091338","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:16:48Z","timestamp":1789460208000},"page":"1338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Regulation of Pancreatic Islet Function by Natural Products Against Type 2 Diabetes Mellitus: Advances and Prospects"],"prefix":"10.3390","volume":"16","author":[{"given":"Guanrong","family":"Qiao","sequence":"first","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicinal Utilization, College of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwaniyi Isaiah","family":"Adejobi","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicinal Utilization, College of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefang","family":"Li","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicinal Utilization, College of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqin","family":"Yang","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicinal Utilization, College of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"He","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicinal Utilization, College of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicinal Utilization, College of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhou","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicinal Utilization, College of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Li","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicinal Utilization, College of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicinal Utilization, College of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicinal Utilization, College of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yu","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicinal Utilization, College of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). 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