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Annona muricata L. (AM) is used for diabetes management. Additional research is required to elucidate its hypoglycemic mechanism; we evaluate its effect on serum leptin, glucagon, insulin, neuropeptide Y concentrations and protein levels of glucagon and insulin in diabetic model. Diabetes was induced in male Wistar rats using a high-fat diet (HFD) combined with 35 mg\/kg streptozotocin (STZ). The animals were randomly assigned to four groups (n = 5): Ctrl (healthy animal), HFD (untreated HFD), AM (50 mg\/kg of AM) and HFD Met (300 mg\/kg of metformin). Treatments were administered orally for four weeks. Serum levels of leptin, glucagon, NPY, insulin, lipid renal and hepatic profiles were quantified before and after treatment. Pancreatic insulin and glucagon content were assessed by immunohistochemistry. Two-way ANOVA with repeated measures (intragroup) and ANOVA (intergroup) were used. The HFD AM group showed lower serum glucose (41.2%), total cholesterol (38.8%), triglycerides (69.6%) and NPY (73.4%) levels than pretreatment values (p &lt; 0.05). Increased serum leptin concentration (53.7%), pancreatic insulin (42.0%), and glucagon (48.0%) protein levels (p &lt; 0.05) were observed. Our study provides additional insights into the hypoglycemic effects of AM and supports its potential use as a complementary treatment for diabetes.<\/jats:p>","DOI":"10.3390\/life16081219","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:05:42Z","timestamp":1784819142000},"page":"1219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Annona muricata L. Leaf Methanolic Extract Modulates Glucose Homeostasis and Improves Pancreatic Hormones Protein Expression in Diabetic Rats"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0395-2333","authenticated-orcid":false,"given":"Luis Rodrigo","family":"Morales-Arzate","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Enfermedades Cr\u00f3nico Degenerativas (IECD), Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7375-9020","authenticated-orcid":false,"given":"Alejandra","family":"Hern\u00e1ndez-Fonseca","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Enfermedades Cr\u00f3nico Degenerativas (IECD), Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2784-322X","authenticated-orcid":false,"given":"Juan Carlos","family":"Pizano-Andrade","sequence":"additional","affiliation":[{"name":"Departamento de Bot\u00e1nica y Zoolog\u00eda, Centro Universitario de Ciencias Biol\u00f3gicas y Agropecuarias, Universidad de Guadalajara, Camino Ram\u00f3n Padilla S\u00e1nchez 2100, Las agujas, Zapopan 44600, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8560-5855","authenticated-orcid":false,"given":"Jos\u00e9 Alfredo","family":"Dom\u00ednguez-Rosales","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Enfermedades Cr\u00f3nico Degenerativas (IECD), Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2319-8470","authenticated-orcid":false,"given":"Zamira Helena","family":"Hern\u00e1ndez-Nazar\u00e1","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Enfermedades Cr\u00f3nico Degenerativas (IECD), Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3760-0806","authenticated-orcid":false,"given":"Efigenia","family":"Montalvo-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio Integral de Investigaci\u00f3n en Alimentos, Divisi\u00f3n de Estudios de Posgrado, Instituto Tecnol\u00f3gico de Tepic, Av. Tecnol\u00f3gico 2595, Tepic 63175, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9851-8961","authenticated-orcid":false,"given":"Carmen Magdalena","family":"Gurrola-D\u00edaz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Enfermedades Cr\u00f3nico Degenerativas (IECD), Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8410-9107","authenticated-orcid":false,"given":"Bertha","family":"Ru\u00edz-Madrigal","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Enfermedades Infectocontagiosas (CIEIC), Departamento de Microbiolog\u00eda y Patolog\u00eda, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9012-8619","authenticated-orcid":false,"given":"Montserrat","family":"Maldonado-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Enfermedades Infectocontagiosas (CIEIC), Departamento de Microbiolog\u00eda y Patolog\u00eda, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9112-5153","authenticated-orcid":false,"given":"Belinda","family":"Vargas-Guerrero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Enfermedades Cr\u00f3nico Degenerativas (IECD), Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee 2 (2025). 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