{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T01:00:22Z","timestamp":1769302822996,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anara AB"},{"name":"MED Sp z o.o."},{"DOI":"10.13039\/501100004442","name":"National Science Centre","doi-asserted-by":"crossref","award":["2021\/41\/N\/NZ9\/01722"],"award-info":[{"award-number":["2021\/41\/N\/NZ9\/01722"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Specialized Private Implantology Clinic Wychowanski Stomatologia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>We aimed to highlight the roles of the pancreatic enzymes, with special reference to amylase, on glucose homeostasis in healthy pigs and in pigs with exocrine pancreatic insufficiency (EPI). Healthy pigs fed a high-fat diet (HFD) were subjected to mixed meal tolerance tests (MMTTs) and pancreatic enzyme treatments, and then blood glucose and insulin concentrations were determined. Following the development of surgically induced EPI, the same experiment was then repeated on the pigs. A significantly lower net postprandial glycemic response was observed in pigs with EPI compared to healthy pigs. Net postprandial glycemic response was not affected by enzyme supplementation during the MMTTs in healthy pigs, but it was affected by adaptation to macronutrient components of the MMTT test meal, both in healthy and EPI pigs. Net postprandial glycemic response and insulin release curves reached higher levels in Creon-treated EPI pigs compared to amylase-treated EPI pigs. In summary, glucose homeostasis mechanisms in EPI pigs were downregulated compared to healthy animals. Creon supplementation during EPI significantly increased postprandial glucose level, while amylase treatment had the opposite effect, which could be explained by its metabolic actions.<\/jats:p>","DOI":"10.3390\/biom16010172","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T17:20:42Z","timestamp":1768929642000},"page":"172","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dependency of Glucose Homeostasis on Pancreatic Enzymes with Special Reference to Amylase; Study on Healthy and Exocrine Pancreatic Insufficient Pigs"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6286-5697","authenticated-orcid":false,"given":"Piotr","family":"Wychowa\u0144ski","sequence":"first","affiliation":[{"name":"Department of Head and Neck and Sensory Organs, Division of Oral Surgery and Implantology, Institute of Clinical Dentistry, Gemelli Foundation for the University Policlinic, Catholic University of the \u201cSacred Heart\u201d, 00168 Rome, Italy"},{"name":"Department of Interventional Dentistry, Collegium Medicum, Nicolaus Copernicus University, 87-100 Bydgoszcz, Poland"},{"name":"Department of Periodontology and Oral Diseases, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0308-3214","authenticated-orcid":false,"given":"Stefan G.","family":"Pierzynowski","sequence":"additional","affiliation":[{"name":"Department of Biology, Lund University, 22362 Lund, Sweden"},{"name":"Anara AB, 23132 Trelleborg, Sweden"},{"name":"Department of Medical Biology, Institute of Rural Health, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4538-3159","authenticated-orcid":false,"given":"Kamil","family":"Zaworski","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jab\u0142onna, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8961-2075","authenticated-orcid":false,"given":"Robert","family":"Gallotto","sequence":"additional","affiliation":[{"name":"Anagram Therapeutics, Inc., Natic, MA 01701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5898-3909","authenticated-orcid":false,"given":"Dominika","family":"Szkopek","sequence":"additional","affiliation":[{"name":"Large Animal Models Laboratory, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jab\u0142onna, Poland"},{"name":"Research Institute of Animal Husbandry, 111121 Balice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8645-1045","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Woli\u0144ski","sequence":"additional","affiliation":[{"name":"Large Animal Models Laboratory, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jab\u0142onna, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5072-016X","authenticated-orcid":false,"given":"Janine","family":"Donaldson","sequence":"additional","affiliation":[{"name":"Anara AB, 23132 Trelleborg, Sweden"},{"name":"Department of Physiology, School of Biomedical Sciences, Faculty of Health Sciences, University of the Witwatersrand,  Johannesburg 2193, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Jacek","sequence":"additional","affiliation":[{"name":"Research Institute of Animal Husbandry, 111121 Balice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3290-339X","authenticated-orcid":false,"given":"Kateryna","family":"Pierzynowska","sequence":"additional","affiliation":[{"name":"Department of Biology, Lund University, 22362 Lund, Sweden"},{"name":"Anara AB, 23132 Trelleborg, Sweden"},{"name":"Department of Medical Biology, Institute of Rural Health, 20-090 Lublin, Poland"},{"name":"Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jab\u0142onna, Poland"},{"name":"Research Institute of Animal Husbandry, 111121 Balice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jin, S., Sha, L., Dong, J., Yi, J., Liu, Y., Guo, Z., and Hu, B. (2020). Effects of Nutritional Strategies on Glucose Homeostasis in Gestational Diabetes Mellitus: A Systematic Review and Network Meta-Analysis. J. Diabetes Res., 6062478.","DOI":"10.1155\/2020\/6062478"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41387-024-00269-3","article-title":"A Mixed Meal Tolerance Test Predicts Onset of Type 2 Diabetes in Southwestern Indigenous Adults","volume":"14","author":"Mitchell","year":"2024","journal-title":"Nutr. Diabetes"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1002\/oby.23503","article-title":"Measuring and Estimating Insulin Resistance in Clinical and Research Settings","volume":"30","author":"Gastaldelli","year":"2022","journal-title":"Obesity"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e219","DOI":"10.1038\/emm.2016.6","article-title":"Pancreatic Regulation of Glucose Homeostasis","volume":"48","author":"Wu","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s002680020338","article-title":"Overview of Glucose Regulation","volume":"25","author":"Tirone","year":"2001","journal-title":"World J. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"van Baak, M.A., Roumans, N.J.T., and Mariman, E.C.M. (2021). Diet Composition, Glucose Homeostasis, and Weight Regain in the YoYo Study. Nutrients, 13.","DOI":"10.3390\/nu13072257"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1177\/1403494810382476","article-title":"Construction and Evaluation of a Self-Contained Index for Assessment of Diet Quality","volume":"38","author":"Kaljonen","year":"2010","journal-title":"Scand. J. Public Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/joim.13333","article-title":"The Mediterranean Diet and Health: A Comprehensive Overview","volume":"290","author":"Willett","year":"2021","journal-title":"J. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Castro-Barquero, S., Ruiz-Le\u00f3n, A.M., Sierra-P\u00e9rez, M., Estruch, R., and Casas, R. (2020). Dietary Strategies for Metabolic Syndrome: A Comprehensive Review. Nutrients, 12.","DOI":"10.3390\/nu12102983"},{"key":"ref_10","first-page":"231","article-title":"Digestion and Absorption","volume":"27","author":"Jackson","year":"2009","journal-title":"Surgery"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e441","DOI":"10.3928\/19382359-20191018-01","article-title":"Pancreatic Malnutrition in Children","volume":"48","author":"Normatov","year":"2019","journal-title":"Pediatr. Ann."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/00004836-199901000-00002","article-title":"Pancreatic Enzymes: Secretion and Luminal Nutrient Digestion in Health and Disease","volume":"28","author":"Layer","year":"1999","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/ame2.12223","article-title":"Advances in Pig Models of Human Diseases","volume":"5","author":"Hou","year":"2022","journal-title":"Anim. Models Exp. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eabd5758","DOI":"10.1126\/scitranslmed.abd5758","article-title":"Importance of the Pig as a Human Biomedical Model","volume":"13","author":"Lunney","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1017\/S0954422416000020","article-title":"Critical Review Evaluating the Pig as a Model for Human Nutritional Physiology","volume":"29","author":"Roura","year":"2016","journal-title":"Nutr. Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pierzynowska, K., Wychowa\u0144ski, P., Zaworski, K., Woli\u0144ski, J., Donaldson, J., and Pierzynowski, S. (2023). Anti-Incretin Gut Features Induced by Feed Supplementation with Alpha-Amylase: Studies on EPI Pigs. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216177"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.4239\/wjd.v14.i9.1341","article-title":"Hypothesis That Alpha-Amylase Evokes Regulatory Mechanisms Originating in the Pancreas, Gut and Circulation, Which Govern Glucose\/Insulin Homeostasis","volume":"14","author":"Pierzynowski","year":"2023","journal-title":"World J. Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Pierzynowska, K.G., Lozinska, L., Woli\u0144ski, J., and Pierzynowski, S. (2018). The Inverse Relationship between Blood Amylase and Insulin Levels in Pigs during Development, Bariatric Surgery, and Intravenous Infusion of Amylase. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198672"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: A Flexible Statistical Power Analysis Program for the Social, Behavioral, and Biomedical Sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2478\/v10039-009-0011-x","article-title":"The Effectiveness of Enzymatic Replacement Therapy Measured by Turbidimetry and the Lipaemic Index in Exocrine Pancreatic Insufficient Young, Growing Pigs, Fed a High-Fat Diet","volume":"54","author":"Donaldson","year":"2009","journal-title":"Adv. Med. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Freedman, S.D., Zaworski, K., Pierzynowska, K., Pierzynowski, S., Gallotto, R., Sathe, M., and Borowitz, D.S. (2023). Validation of an Omega-3 Substrate Challenge Absorption Test as an Indicator of Global Fat Lipolysis. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0284651"},{"key":"ref_22","unstructured":"(2012). Nutrient Requirements of Swine\/Committee on Nutrient Requirements of Swine, The National Academies Press. [11th rev. ed.]. Board on Agriculture and Natural Resources, Division on Earth and Life Studies."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Szczurek, P., Mosiichuk, N., Woli\u0144ski, J., Yatsenko, T., Grujic, D., Lozinska, L., Pieszka, M., \u015awi\u0119ch, E., Pierzynowski, S.G., and Goncharova, K. (2017). Oral Uricase Eliminates Blood Uric Acid in the Hyperuricemic Pig Model. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179195"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pierzynowska, K., Pierzynowski, S., Zaworski, K., Gallotto, R., Sathe, M., Freedman, S.D., and Borowitz, D. (2025). Validation of Dietary Whey Protein Substrate Challenge Absorption Test as an Indicator of Proteolysis. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0323730"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1016\/j.athoracsur.2015.11.024","article-title":"Adjust for Multiple Comparisons? It\u2019s Not That Simple","volume":"101","author":"Althouse","year":"2016","journal-title":"Ann. Thorac. Surg."},{"key":"ref_26","first-page":"391","article-title":"Oral Glucose Tolerance Testing","volume":"41","author":"Phillips","year":"2012","journal-title":"Aust. Fam. Physician"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lages, M., Barros, R., Moreira, P., and Guarino, M.P. (2022). Metabolic Effects of an Oral Glucose Tolerance Test Compared to the Mixed Meal Tolerance Tests: A Narrative Review. Nutrients, 14.","DOI":"10.3390\/nu14102032"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.diabres.2011.09.002","article-title":"Postprandial Metabolic Responses to Mixed versus Liquid Meal Tests in Healthy Men and Men with Type 2 Diabetes","volume":"94","author":"Brodovicz","year":"2011","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"766","DOI":"10.7326\/0003-4819-148-10-200805200-00009","article-title":"Screening for Gestational Diabetes Mellitus: A Systematic Review for the U.S. Preventive Services Task Force","volume":"148","author":"Hillier","year":"2008","journal-title":"Ann. Intern. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ramos-Levi, A.M., Rubio-Herrera, M.A., Mat\u00eda-Mart\u00edn, P., P\u00e9rez-Ferre, N., Marcuello, C., S\u00e1nchez-Pernaute, A., Torres-Garc\u00eda, A.J., and Calle-Pascual, A.L. (2023). Mixed Meal Tolerance Test Versus Continuous Glucose Monitoring for an Effective Diagnosis of Persistent Post-Bariatric Hypoglycemia. JCM, 12.","DOI":"10.3390\/jcm12134295"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1089\/dia.2023.0390","article-title":"Continuous Glucose Monitoring Systems in Noninsulin-Treated People with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"26","author":"Ferreira","year":"2024","journal-title":"Diabetes Technol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41574-024-00973-1","article-title":"Continuous Glucose Monitoring for the Routine Care of Type 2 Diabetes Mellitus","volume":"20","author":"Ajjan","year":"2024","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/s41598-025-30743-6","article-title":"Noninvasive Subterahertz Glucose Monitoring Using a Communication Inspired Eye Diagram","volume":"16","author":"Lee","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/BF02787526","article-title":"Oral Pancreatic Enzyme Therapy in the Control of Diabetes Mellitus in Tropical Calculous Pancreatitis","volume":"24","author":"Mohan","year":"1998","journal-title":"Int. J. Pancreatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17439","DOI":"10.1074\/jbc.M114.594937","article-title":"Pancreatic \u03b1-Amylase Controls Glucose Assimilation by Duodenal Retrieval through N-Glycan-Specific Binding, Endocytosis, and Degradation","volume":"290","author":"Date","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"23104","DOI":"10.1074\/jbc.M111.314658","article-title":"Functional Regulation of Sugar Assimilation by N-Glycan-Specific Interaction of Pancreatic \u03b1-Amylase with Glycoproteins of Duodenal Brush Border Membrane","volume":"287","author":"Hirano","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Bonnefond, A., Yengo, L., Dechaume, A., Canouil, M., Castelain, M., Roger, E., Allegaert, F., Caiazzo, R., Raverdy, V., and Pigeyre, M. (2017). Relationship between Salivary\/Pancreatic Amylase and Body Mass Index: A Systems Biology Approach. BMC Med., 15.","DOI":"10.1186\/s12916-017-0784-x"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/dom.12729","article-title":"Mechanisms of \u0392-cell Functional Adaptation to Changes in Workload","volume":"18","author":"Wortham","year":"2016","journal-title":"Diabetes Obes. Metab."},{"key":"ref_39","first-page":"681","article-title":"Enteral Pancreatic-like Enzymes of Microbial Origin Affect Insulin Release during an Intravenous Glucose Tolerance Test","volume":"7","author":"Pierzynowski","year":"2016","journal-title":"J. Diabetes Metab."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/172\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T05:16:52Z","timestamp":1769231812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["biom16010172"],"URL":"https:\/\/doi.org\/10.3390\/biom16010172","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]}}}