{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:24:16Z","timestamp":1781717056141,"version":"3.54.5"},"reference-count":56,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UNAM DGAPA-PAPIIT","award":["IN214225"],"award-info":[{"award-number":["IN214225"]}]},{"name":"UNAM DGAPA-PAPIIT","award":["IN213222"],"award-info":[{"award-number":["IN213222"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Ethnopharmacological studies indicates that plant-based infusions are usually consumed by some people in advanced stages of diabetes, that is, when poor pancreatic dysfunction coexists with insulin resistance (IR). Current treatments aim to prevent \u03b2-cell deterioration by promoting improved insulin function and\/or enhancing pancreatic function to avoid the development of hyperglycemia. Therefore, Croton guatemalensis (Cg) and Eryngium cymosum (Ec), two medicinal plants with potential insulin-sensitizing effects described in previous studies, were assessed on parameters related to IR and on the architecture of pancreatic islets in rats exposed to a syrup containing 8.8% glucose and 5.2% fructose in drinking water. Methods: After an 8-week exposure to syrup, plant extracts were orally administered for four weeks at traditional doses (Cg: 30 mg\/kg body weight; Ec: 470 mg\/kg body weight). Body weight, food intake, and drinking water consumption were monitored. At the end of the study, IR surrogate indices were calculated, metabolic assays were performed, and white adipose tissues, liver, gastrocnemius muscle, and pancreas were extracted in fasting and postprandial state for lipid quantification (liver), measurement of Akt phosphorylation status by western blot (liver and muscle), and determination of insulin content by immunohistochemistry (pancreatic islets). Results: Both species decreased hepatic lipid content without promoting significant changes in visceral adiposity. Although they did not improve surrogate markers of fasting IR, both ameliorated insulin function, glucose tolerance, and restored the glucose-stimulated insulin secretory response in metabolic tests. Cg restored the insulin signaling response in liver and muscle, whereas Ec only did so in muscle. Moreover, both appeared to enhance insulin pancreatic content or restore pancreatic islet population. Conclusions: Cg and Ec can reverse the IR phenotype in a tissue-specific manner and improve pancreatic function.<\/jats:p>","DOI":"10.3390\/ph18101433","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T12:15:31Z","timestamp":1758716131000},"page":"1433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tissue-Specific Enhancement of Insulin Function and Restoration of Glucose-Stimulated Insulin Secretion by Croton guatemalensis Lotsy and Eryngium cymosum F. Delaroche"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8464-5951","authenticated-orcid":false,"given":"Fernanda Artemisa","family":"Espinoza-Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Ciudad Universitaria, Coyoac\u00e1n, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina Daniela","family":"Moreno-Vargas","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Ciudad Universitaria, Coyoac\u00e1n, Mexico City 04510, Mexico"},{"name":"Posgrado en Ciencias Biol\u00f3gicas, Unidad de Posgrado, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Edificio D, 1\u00b0 Piso, Circuito de Posgrados, Ciudad Universitaria, Coyoac\u00e1n, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1222-2615","authenticated-orcid":false,"given":"Andrea","family":"D\u00edaz-Villase\u00f1or","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Gen\u00f3mica y Toxicolog\u00eda Ambiental, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Ciudad Universitaria, Coyoac\u00e1n, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9183-5326","authenticated-orcid":false,"given":"Gerardo","family":"Mata-Torres","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Ciudad Universitaria, Coyoac\u00e1n, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6364-1903","authenticated-orcid":false,"given":"Jazm\u00edn","family":"Samario-Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Ciudad Universitaria, Coyoac\u00e1n, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1638-3443","authenticated-orcid":false,"given":"Adolfo","family":"Andrade-Cetto","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Ciudad Universitaria, Coyoac\u00e1n, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41392-022-01073-0","article-title":"Trends in Insulin Resistance: Insights into Mechanisms and Therapeutic Strategy","volume":"7","author":"Li","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4093\/dmj.2021.0280","article-title":"Insulin Resistance: From Mechanisms to Therapeutic Strategies","volume":"46","author":"Lee","year":"2022","journal-title":"Diabetes Metab. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"111315","DOI":"10.1016\/j.biopha.2021.111315","article-title":"Adipose Tissue and Insulin Resistance in Obese","volume":"137","author":"Ahmed","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"154892","DOI":"10.1016\/j.metabol.2021.154892","article-title":"Insulin Resistance and Insulin Sensitizing Agents","volume":"125","author":"Mastrototaro","year":"2021","journal-title":"Metabolism"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Dimitriadis, G.D., Maratou, E., Kountouri, A., Board, M., and Lambadiari, V. (2021). Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach. Nutrients, 13.","DOI":"10.3390\/nu13010159"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"E2","DOI":"10.1152\/ajpendo.00441.2021","article-title":"Hyperinsulinemia: Beneficial or Harmful or Both on Glucose Homeostasis","volume":"323","author":"Xing","year":"2022","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.tips.2020.09.001","article-title":"Metformin and Systemic Metabolism","volume":"41","author":"He","year":"2020","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/bs.podrm.2015.11.002","article-title":"Pioglitazone","volume":"Volume 41","author":"Brittain","year":"2016","journal-title":"Profiles of Drug Substances, Excipients and Related Methodology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1007\/s00125-018-4658-3","article-title":"Novel Approaches to Restore Beta Cell Function in Prediabetes and Type 2 Diabetes","volume":"61","author":"Salunkhe","year":"2018","journal-title":"Diabetologia"},{"key":"ref_10","first-page":"5970358","article-title":"Chronic Antihyperglycemic Effect Exerted by Traditional Extracts of Three Mexican Medicinal Plants","volume":"2022","year":"2022","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1007\/s00125-023-06064-6","article-title":"The Impact of Taxing Sugar-Sweetened Beverages on Diabetes: A Critical Review","volume":"67","year":"2024","journal-title":"Diabetologia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1080\/10408363.2019.1711360","article-title":"Fructose and Hepatic Insulin Resistance","volume":"57","author":"Softic","year":"2020","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hieronimus, B., Medici, V., Lee, V., Nunez, M.V., Sigala, D.M., Bremer, A.A., Cox, C.L., Keim, N.L., Schwarz, J., and Pacini, G. (2024). Effects of Consuming Beverages Sweetened with Fructose, Glucose, High-Fructose Corn Syrup, Sucrose, or Aspartame on OGTT-Derived Indices of Insulin Sensitivity in Young Adults. Nutrients, 16.","DOI":"10.3390\/nu16010151"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"114339","DOI":"10.1016\/j.jep.2021.114339","article-title":"Contribution of Fasting and Postprandial Glucose-Lowering Mechanisms to the Acute Hypoglycemic Effect of Traditionally Used Eryngium cymosum F. Delaroche","volume":"279","author":"Mata","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Moreno-Vargas, A.D., Andrade-Cetto, A., Espinoza-Hern\u00e1ndez, F.A., and Mata-Torres, G. (2024). Proposed Mechanisms of Action Participating in the Hypoglycemic Effect of the Traditionally Used Croton Guatemalensis Lotsy and Junceic Acid, Its Main Compound. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1436927"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.jep.2014.11.021","article-title":"Ethnopharmacological Field Study of the Plants Used to Treat Type 2 Diabetes among the Cakchiquels in Guatemala","volume":"159","author":"Cruz","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Romo-P\u00e9rez, A., Escand\u00f3n-Rivera, S.M., Miranda, L.D., and Andrade-Cetto, A. (2022). Phytochemical Study of Eryngium cymosum F. Delaroche and the Inhibitory Capacity of Its Main Compounds on Two Glucose-Producing Pathway Enzymes. Plants, 11.","DOI":"10.3390\/plants11070992"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Escand\u00f3n-Rivera, S.M., Andrade-Cetto, A., Rosas-Ram\u00edrez, D.G., and Arregu\u00edn-Espinosa, R. (2022). Phytochemical Screening and Isolation of New Ent-Clerodane Diterpenoids from Croton Guatemalensis Lotsy. Plants, 11.","DOI":"10.3390\/plants11223159"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102581","DOI":"10.1016\/j.dsx.2022.102581","article-title":"Challenges in the Diagnosis of Insulin Resistance: Focusing on the Role of HOMA-IR and Tryglyceride\/Glucose Index","volume":"16","author":"Tahapary","year":"2022","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Betim Cazarin, C.B. (2022). Basic Protocols in Foods and Nutrition, Springer. Methods and Protocols in Food Science.","DOI":"10.1007\/978-1-0716-2345-9"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"935","DOI":"10.2337\/diabetes.52.4.935","article-title":"Defective Signaling Through Akt-2 and -3 But Not Akt-1 in Insulin-Resistant Human Skeletal Muscle","volume":"52","author":"Brozinick","year":"2003","journal-title":"Diabetes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.cell.2017.04.001","article-title":"AKT\/PKB Signaling: Navigating the Network","volume":"169","author":"Manning","year":"2017","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1017\/S1462399411002109","article-title":"PI3K\/AKT, MAPK and AMPK Signalling: Protein Kinases in Glucose Homeostasis","volume":"14","author":"Schultze","year":"2012","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e13652","DOI":"10.14814\/phy2.13652","article-title":"AKT2 Is the Predominant AKT Isoform Expressed in Human Skeletal Muscle","volume":"6","author":"Matheny","year":"2018","journal-title":"Physiol. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"39230","DOI":"10.1038\/srep39230","article-title":"Insulin-Induced Effects on the Subcellular Localization of AKT1, AKT2 and AS160 in Rat Skeletal Muscle","volume":"6","author":"Zheng","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1586\/ecp.12.74","article-title":"Polypharmacology: Drug Discovery for the Future","volume":"6","author":"Reddy","year":"2013","journal-title":"Expert. Rev. Clin. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"109443","DOI":"10.1016\/j.biopha.2019.109443","article-title":"Rosmarinic Acid Inhibits Proliferation and Invasion of Hepatocellular Carcinoma Cells SMMC 7721 via PI3K\/AKT\/MTOR Signal Pathway","volume":"120","author":"Wang","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Casares, R.M., Hern\u00e1ndez-V\u00e1zquez, L., Mandujano, A., S\u00e1nchez-P\u00e9rez, L., P\u00e9rez-Guti\u00e9rrez, S., and P\u00e9rez-Ramos, J. (2023). Anti-Inflammatory and Cytotoxic Activities of Clerodane-Type Diterpenes. Molecules, 28.","DOI":"10.3390\/molecules28124744"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1172\/JCI96702","article-title":"Fructose Metabolism and Metabolic Disease","volume":"128","author":"Hannou","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","article-title":"Mechanisms of Insulin Action and Insulin Resistance","volume":"98","author":"Petersen","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12933-018-0738-4","article-title":"Actions of Metformin and Statins on Lipid and Glucose Metabolism and Possible Benefit of Combination Therapy","volume":"17","author":"Groen","year":"2018","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s00535-013-0758-5","article-title":"Mechanisms of Hepatic Triglyceride Accumulation in Non-Alcoholic Fatty Liver Disease","volume":"48","author":"Kawano","year":"2013","journal-title":"J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nyandwi, J.B., Ko, Y.S., Jin, H., Yun, S.P., Park, S.W., and Kim, H.J. (2021). Rosmarinic Acid Exhibits a Lipid-Lowering Effect by Modulating the Expression of Reverse Cholesterol Transporters and Lipid Metabolism in High-Fat Diet-Fed Mice. Biomolecules, 11.","DOI":"10.3390\/biom11101470"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.mce.2014.09.024","article-title":"A Clerodane Diterpene Inhibit Adipogenesis by Cell Cycle Arrest and Ameliorate Obesity in C57BL\/6 Mice","volume":"399","author":"Beg","year":"2015","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_35","first-page":"167","article-title":"Association between Polymorphism in the AKT1 Gene and Type 2 Diabetes Mellitus in a Mexican Population","volume":"2","year":"2015","journal-title":"Rev. Mex. Endocrinol. Metab. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1152\/ajpendo.00374.2009","article-title":"Increased Basal Level of Akt-Dependent Insulin Signaling May Be Responsible for the Development of Insulin Resistance","volume":"297","author":"Liu","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s00125-012-2811-y","article-title":"Impaired Akt Phosphorylation in Insulin-Resistant Human Muscle Is Accompanied by Selective and Heterogeneous Downstream Defects","volume":"56","author":"Tonks","year":"2013","journal-title":"Diabetologia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1007\/s00125-007-0913-8","article-title":"Isoform-Specific Defects of Insulin Stimulation of Akt\/Protein Kinase B (PKB) in Skeletal Muscle Cells from Type 2 Diabetic Patients","volume":"51","author":"Cozzone","year":"2008","journal-title":"Diabetologia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1002\/mnfr.201200500","article-title":"Cocoa Flavonoids Improve Insulin Signalling and Modulate Glucose Production via AKT and AMPK in HepG2 Cells","volume":"57","author":"Bravo","year":"2013","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Den Hartogh, D.J., Vlavcheski, F., and Tsiani, E. (2023). Muscle Cell Insulin Resistance Is Attenuated by Rosmarinic Acid: Elucidating the Mechanisms Involved. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065094"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1038\/s12276-023-01043-8","article-title":"Reversing Pancreatic \u03b2-Cell Dedifferentiation in the Treatment of Type 2 Diabetes","volume":"55","author":"Son","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.2337\/db05-1602","article-title":"Chronic Inhibition of Dipeptidyl Peptidase-4 with a Sitagliptin Analog Preserves Pancreatic \u03b2-Cell Mass and Function in a Rodent Model of Type 2 Diabetes","volume":"55","author":"Mu","year":"2006","journal-title":"Diabetes"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7416529","DOI":"10.1155\/2020\/7416529","article-title":"Eugenol Improves Insulin Secretion and Content of Pancreatic Islets from Male Mouse","volume":"2020","author":"Oroojan","year":"2020","journal-title":"Int. J. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"117580","DOI":"10.1016\/j.jep.2023.117580","article-title":"Exploring the Hypoglycemic Mechanism of Chlorogenic Acids from Pyrrosia Petiolosa (Christ) Ching on Type 2 Diabetes Mellitus Based on Network Pharmacology and Transcriptomics Strategy","volume":"322","author":"He","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e19234","DOI":"10.1016\/j.heliyon.2023.e19234","article-title":"Rosemarinic Acid Protects \u03b2-Cell from STZ-Induced Cell Damage via Modulating NF-\u03ba\u03b2 Pathway","volume":"9","author":"Anjum","year":"2023","journal-title":"Heliyon"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10339","DOI":"10.1021\/acs.jafc.3c07311","article-title":"Platycodin D Ameliorates Type 2 Diabetes-Induced Myocardial Injury by Activating the AMPK Signaling Pathway","volume":"72","author":"Wang","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s13105-019-00706-3","article-title":"The Relevance of AMP-Activated Protein Kinase in Insulin-Secreting \u03b2 Cells: A Potential Target for Improving \u03b2 Cell Function?","volume":"75","author":"Szkudelski","year":"2019","journal-title":"J. Physiol. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.fct.2018.09.064","article-title":"Review on Rosmarinic Acid Extraction, Fractionation and Its Anti-Diabetic Potential","volume":"121","author":"Ngo","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Acquaviva, R., Malfa, G.A., Loizzo, M.R., Xiao, J., Bianchi, S., and Tundis, R. (2022). Advances on Natural Abietane, Labdane and Clerodane Diterpenes as Anti-Cancer Agents: Sources and Mechanisms of Action. Molecules, 27.","DOI":"10.3390\/molecules27154791"},{"key":"ref_50","first-page":"2168603","article-title":"Hypoglycemic Activity of Medicinal Plants Used among the Cakchiquels in Guatemala for the Treatment of Type 2 Diabetes","volume":"2019","author":"Cruz","year":"2019","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_51","unstructured":"National Research Council (US), and Committee for the Update of the Guide for the Care and Use of Laboratory Animals (2011). Guide for the Care and Use of Laboratory Animals, The National Academies Press. [8th ed.]."},{"key":"ref_52","first-page":"292","article-title":"Weaning STZ-Induced Hyperglycemic Rats Fed Glucose-Fructose Syrup As a Novel Model for the Natural History of Type 2 Diabetes","volume":"2","year":"2021","journal-title":"Pharmacologyonline"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1177\/1932296818805074","article-title":"Insulin Units and Conversion Factors: A Story of Truth, Boots, and Faster Half-Truths","volume":"13","author":"Knopp","year":"2019","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.2337\/diacare.27.6.1487","article-title":"Use and Abuse of HOMA Modeling","volume":"27","author":"Wallace","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Betim Cazarin, C.B. (2022). The Assessment of Glucose Homeostasis in Rodents: Glucose, Insulin and Pyruvate Tolerance Tests. Basic Protocols in Foods and Nutrition, Springer.","DOI":"10.1007\/978-1-0716-2345-9"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.diabres.2005.10.005","article-title":"Insulinogenic Indices from Insulin and C-Peptide: Comparison of Beta-Cell Function from OGTT and IVGTT","volume":"72","author":"Tura","year":"2006","journal-title":"Diabetes Res. Clin. Pract."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/10\/1433\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:48:54Z","timestamp":1760035734000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/10\/1433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":56,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ph18101433"],"URL":"https:\/\/doi.org\/10.3390\/ph18101433","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,24]]}}}