{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T08:28:23Z","timestamp":1769329703476,"version":"3.49.0"},"reference-count":35,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anara AB (Sweden)","award":["2021\/41\/N\/NZ9\/01722"],"award-info":[{"award-number":["2021\/41\/N\/NZ9\/01722"]}]},{"name":"MED Sp z o.o. (Poland)","award":["2021\/41\/N\/NZ9\/01722"],"award-info":[{"award-number":["2021\/41\/N\/NZ9\/01722"]}]},{"DOI":"10.13039\/501100004281","name":"National Science Centre (Poland)","doi-asserted-by":"publisher","award":["2021\/41\/N\/NZ9\/01722"],"award-info":[{"award-number":["2021\/41\/N\/NZ9\/01722"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The acini-islet-acinar (AIA) axis concept justifies the anatomical placement of the Langerhans islets within the exocrine pancreatic parenchyma and explains the existence of the pancreas as a single organ. Amylase has been suggested to play a key role as an anti-incretin factor. Oral glucose tolerance tests (OGTT) were performed on 18 piglets in both a healthy (prior to pancreatic duct ligation (PDL) surgery, study Day 10) and an exocrine pancreatic insufficient (EPI) state (30 days after PDL, study Day 48)). Amylase (4000 units\/feeding) or Creon\u00ae (100,000 units\/feeding) was administered to pigs with the morning and evening meals, according to study design randomization, for 37 days following the first OGTT. Blood glucose levels, as well as plasma levels of insulin, GLP-1, and GIP, were measured, and the HOMA-IR index was calculated. EPI status did not affect the area under the curve (AUC) of insulin release, fasting insulin levels, or the HOMA-IR index, while amylase supplementation led to a significant (p &lt; 0.05) decrease in the above-mentioned parameters. At the same time, EPI led to a significant (p &lt; 0.05) increase in GLP-1 levels, and neither amylase nor Creon\u00ae supplementation had any effects on this EPI-related increase. Fasting plasma levels of GIP were not affected by EPI; however, the GIP response in EPI and Amylase-treated EPI animals was significantly lower (p &lt; 0.05) when compared to that of the intact, healthy pigs. Orally administered amylase induces gut anti-incretin action, normalizing glucose homeostasis and reducing HOMA-IR as a long-term outcome, thus lowering the risk of diabetes type II development. Amylase has long-lasting anti-incretin effects, and one could consider the existence of a long-lasting gut memory for amylase, which decreases hyperinsulinemia and hyperglycemia for up to 16 h after the last exposure of the gut to amylase.<\/jats:p>","DOI":"10.3390\/ijms242216177","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T02:02:42Z","timestamp":1699840962000},"page":"16177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Anti-Incretin Gut Features Induced by Feed Supplementation with Alpha-Amylase: Studies on EPI Pigs"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3290-339X","authenticated-orcid":false,"given":"Kateryna","family":"Pierzynowska","sequence":"first","affiliation":[{"name":"Department of Biology, Lund University, 223 62 Lund, Sweden"},{"name":"Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jab\u0142onna, Poland"},{"name":"Anara AB, 231 32 Trelleborg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Wychowa\u0144ski","sequence":"additional","affiliation":[{"name":"Anara AB, 231 32 Trelleborg, Sweden"},{"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 Oral Surgery, Medical University of Gda\u0144sk, 80-211 Gda\u0144sk, Poland"},{"name":"Specialized Private Implantology Clinic Wychowanski Stomatologia, 02-517 Warsaw, 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"}]},{"given":"Jaros\u0142aw","family":"Woli\u0144ski","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"},{"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, 231 32 Trelleborg, Sweden"},{"name":"School of Physiology, Faculty of Health Sciences, University of the Witwatersrand (WITS), Johannesburg 2050, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0308-3214","authenticated-orcid":false,"given":"Stefan","family":"Pierzynowski","sequence":"additional","affiliation":[{"name":"Department of Biology, Lund University, 223 62 Lund, Sweden"},{"name":"Anara AB, 231 32 Trelleborg, Sweden"},{"name":"Department of Medical Biology, Institute of Rural Health, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1080\/00365521.1976.12097146","article-title":"Effects on Exocrine and Endocrine Rat Pancreas of Long-Term Administration of CCK-PZ (Cholecystokinin-Pancreozymin) or Synthetic Octapeptide\u2014CCK-PZ","volume":"11","author":"Lundquist","year":"1976","journal-title":"Scand J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1093\/jn\/113.4.921","article-title":"Pancreatic Enzyme Activity in Obese and Lean Zucker Rats: A Developmental Study","volume":"113","author":"Schneeman","year":"1983","journal-title":"J. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/BF02788453","article-title":"Serum Levels of Pancreatic Enzymes in Lean And Obese Subjects","volume":"3","author":"Kondo","year":"1988","journal-title":"Int. J. Pancreatol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nakajima, K., Muneyuki, T., Munakata, H., and Kakei, M. (2011). Revisiting the Cardiometabolic Relevance of Serum Amylase. BMC Res. Notes, 4.","DOI":"10.1186\/1756-0500-4-419"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/1475-2840-11-80","article-title":"Latent Associations of Low Serum Amylase with Decreased Plasma Insulin Levels and Insulin Resistance in Asymptomatic Middle-Aged Adults","volume":"11","author":"Muneyuki","year":"2012","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"853","DOI":"10.3945\/jn.111.156984","article-title":"High Endogenous Salivary Amylase Activity is Associated with Improved Glycemic Homeostasis Following Starch Ingestion in Adults","volume":"142","author":"Mandel","year":"2012","journal-title":"J. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/ng.2939","article-title":"Low Copy Number of the Salivary Amylase Gene Predisposes to Obesity","volume":"46","author":"Falchi","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1111\/dme.12808","article-title":"Association Between Salivary Amylase (AMY1) Gene Copy Numbers and Insulin Resistance in Asymptomatic Korean Men","volume":"32","author":"Choi","year":"2015","journal-title":"Diabet. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/17446651.2018.1499466","article-title":"Human Amylase Gene Copy Number Variation as a Determinant of Metabolic State","volume":"13","author":"Elder","year":"2018","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107974","DOI":"10.1016\/j.diabres.2019.107974","article-title":"Low Serum Amylase, Lipase, and Trypsin as Biomarkers of Metabolic Disorders: A Systematic Review and Meta-Analysis","volume":"159","author":"Ko","year":"2020","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.2147\/DMSO.S339604","article-title":"Association of Serum Amylase Activity and the Copy Number Variation of AMY1\/2A\/2B with Metabolic Syndrome in Chinese Adults","volume":"14","author":"Zhan","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"112","DOI":"10.4239\/wjd.v7.i6.112","article-title":"Low Serum Amylase and Obesity, Diabetes and Metabolic Syndrome: A Novel Interpretation","volume":"7","author":"Nakajima","year":"2016","journal-title":"World J. Diabetes"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"980","DOI":"10.2337\/diab.34.10.980","article-title":"The Insulin-Pancreatic Acinar Axis","volume":"34","author":"Williams","year":"1985","journal-title":"Diabetes"},{"key":"ref_14","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."},{"key":"ref_15","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_16","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_17","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_18","doi-asserted-by":"crossref","first-page":"100396","DOI":"10.1016\/j.animal.2021.100396","article-title":"Effects of Exogenous \u03b1-(1,4)-Amylase on the Utilisation of Corn Starch and Glucose Metabolism in Broiler Chickens","volume":"15","author":"Zhou","year":"2021","journal-title":"Animal"},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41387-018-0062-9","article-title":"Glucose Homeostasis Dependency on Acini\u2013Islet\u2013Acinar (AIA) Axis Communication: A New Possible Pathophysiological Hypothesis Regarding Diabetes Mellitus","volume":"8","author":"Pierzynowski","year":"2018","journal-title":"Nutr. Diabetes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1002\/jcb.29357","article-title":"A-Amylase Expressed in Human Small Intestinal Epithelial Cells is Essential for Cell Proliferation and Differentiation","volume":"121","author":"Date","year":"2020","journal-title":"J. Cell Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1111\/jgh.15748","article-title":"Low Serum Pancreatic Amylase Levels as a Novel Latent Risk Factor for Colorectal Adenoma in Non-Alcohol Drinkers","volume":"37","author":"Sasaki","year":"2022","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1111\/bpa.12597","article-title":"Brain Alpha-Amylase: A Novel Energy Regulator Important in Alzheimer Disease?","volume":"28","author":"Byman","year":"2018","journal-title":"Brain Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e13433","DOI":"10.1111\/acel.13433","article-title":"Neuronal A-Amylase is Important for Neuronal Activity and Glycogenolysis and Reduces in Presence of Amyloid Beta Pathology","volume":"20","author":"Byman","year":"2021","journal-title":"Aging Cell"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pierzynowska, K., Thomasson, S., and Oredsson, S. (2022). Alpha-Amylase Inhibits Cell Proliferation and Glucose Uptake in Human Neuroblastoma Cell Lines. Biomed. Res. Int., 2022.","DOI":"10.1155\/2022\/4271358"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e218860","DOI":"10.1001\/jamanetworkopen.2021.8860","article-title":"Metabolically Healthy Obesity Redefined","volume":"4","author":"Rodriguez","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1093\/toxsci\/kfx233","article-title":"Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic","volume":"162","author":"Mendrick","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1097\/00000658-200211000-00003","article-title":"Potential of Surgery for Curing Type 2 Diabetes Mellitus","volume":"236","author":"Rubino","year":"2002","journal-title":"Ann. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S290","DOI":"10.2337\/dc08-s271","article-title":"Is Type 2 Diabetes an Operable Intestinal Disease?","volume":"31","author":"Rubino","year":"2008","journal-title":"Diabetes Care"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.2337\/db14-0402","article-title":"Is the Gut the \u201cSweet Spot\u201d for the Treatment of Diabetes?","volume":"63","author":"Rubino","year":"2014","journal-title":"Diabetes"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.2337\/db13-0969","article-title":"Gastric Bypass Improves \u0392-Cell Function and Increases \u0392-Cell Mass in A Porcine Model","volume":"63","author":"Lindqvist","year":"2014","journal-title":"Diabetes"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.2337\/db13-0856","article-title":"Duodenal-Jejunal Bypass and Jejunectomy Improve Insulin Sensitivity in Goto-Kakizaki Diabetic Rats without Changes in Incretins or Insulin Secretion","volume":"63","author":"Salinari","year":"2014","journal-title":"Diabetes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.2337\/db17-0234","article-title":"Downregulation of Insulin Sensitivity After Oral Glucose Administration: Evidence for the Anti-Incretin Effect","volume":"66","author":"Salinari","year":"2017","journal-title":"Diabetes"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"387","DOI":"10.3389\/fendo.2018.00387","article-title":"The Origin and Understanding of the Incretin Concept","volume":"9","author":"Rehfeld","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1007\/s00125-023-05906-7","article-title":"The Expanding Incretin Universe: From Basic Biology to Clinical Translation","volume":"66","author":"Drucker","year":"2023","journal-title":"Diabetologia"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16177\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:21:11Z","timestamp":1760131271000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,10]]},"references-count":35,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ijms242216177"],"URL":"https:\/\/doi.org\/10.3390\/ijms242216177","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,10]]}}}