{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:08:05Z","timestamp":1788404885249,"version":"build-2803163510"},"reference-count":88,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFF1300504"],"award-info":[{"award-number":["2022YFF1300504"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background and Methods: To address the need for dietary interventions in sub-healthy populations and promote sustainable utilization of agricultural by-products, we isolated Pinus pumila hypoglycemic peptide (PHP) from nut oil meal through enzymatic extraction, ion exchange and gel chromatography purification, and simulated gastric digestion. Results: PHP exhibited significant inhibitory activity against \u03b1-amylase and \u03b1-glucosidase. In type 2 diabetic mice, PHP significantly ameliorated the \u201cthree-more-one-less\u201d syndrome, reduced glycosylated hemoglobin and insulin levels, mitigated liver and kidney tissue lesions, and improved glucose and lipid metabolic disorders\u2014effects partly supported by its enhancement of intestinal barrier function via restoring gut microbiota diversity. Gut microbiota analysis revealed that PHP exerts hypoglycemic effects by regulating gut microbial composition: increasing SCFA-producing taxa, reducing pro-inflammatory\/metabolic disorder-associated taxa, and normalizing the Firmicutes\/Bacteroidetes ratio. KEGG pathway analysis demonstrated that PHP mediates synergistic hypoglycemic effects by regulating carbohydrate metabolism, amino acid metabolism, and cofactor\/vitamin metabolism. Conclusions: This work provides a theoretical foundation for developing natural functional foods from agricultural by-products, supporting PHP\u2019s potential as a dietary supplement for metabolic regulation.<\/jats:p>","DOI":"10.3390\/nu17172903","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T08:40:15Z","timestamp":1757407215000},"page":"2903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Hypoglycemic Peptide from Pinus pumila Nut Oil Meal Improves Glycolipid Metabolism via Multi-Dimensional Regulation in Type 2 Diabetic Mice"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1496-0393","authenticated-orcid":false,"given":"Zhe-Xuan","family":"Mu","sequence":"first","affiliation":[{"name":"Department of Special Food and Drug and Biochemical Innovation Research Center, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Zhou","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Special Food and Drug and Biochemical Innovation Research Center, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Special Food and Drug and Biochemical Innovation Research Center, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Special Food and Drug and Biochemical Innovation Research Center, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hong","family":"Lv","sequence":"additional","affiliation":[{"name":"Forestry and Grassland Germplasm Resources Research Center, Heilongjiang Academy of Forestry, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Special Food and Drug and Biochemical Innovation Research Center, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1262-2195","authenticated-orcid":false,"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Special Food and Drug and Biochemical Innovation Research Center, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Prevalence of obesity in the United States, 2009\u20132010","volume":"2013","author":"Ogden","year":"2012","journal-title":"NCHS Data Brief"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"f13","DOI":"10.1093\/chromsci\/bmaf013","article-title":"Analytical Methods for Estimating Metformin Hydrochloride, Pioglitazone and Teneligliptin in Diabetes Management: A Comprehensive Review","volume":"63","author":"Pandya","year":"2025","journal-title":"J. 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