Interaction of the Endocrine and Exocrine Parts of the Pancreas

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The pancreas plays a key role in the endocrine system of animals and in the digestion and absorption of nutrients. The exocrine and endocrine pancreas are structurally separate from each other, but numerous studies suggest anatomical and functional connections between these parts. Previously, less attention was paid to these interactions, but the pancreas is now viewed as a single organ consisting of functionally related components that coordinates endocrine and exocrine responses. Our review examines the latest data indicating the functional connection and mutual influence of the endocrine and exocrine parts of the pancreas. In addition, we will also look at the impact of SARS-CoV-2 infection on pancreatic function.

Full Text

Restricted Access

About the authors

A. Mostafa

GIGA Research Centre, Université de Liège

Email: deyevie@gmail.com
Belgium, Liège

E. A. Gantsova

Рeoples’ Friendship University of Russia

Email: deyevie@gmail.com

Research Institute of Molecular and Cellular Medicine

Russian Federation, Moscow

O. V. Serova

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences Russian Academy of Sciences

Email: deyevie@gmail.com
Russian Federation, Moscow

T. Mohammad

Moscow Institute of Physics and Technology

Email: deyevie@gmail.com
Russian Federation, Moscow

I. E. Deyev

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences Russian Academy of Sciences

Author for correspondence.
Email: deyevie@gmail.com
Russian Federation, Moscow

References

  1. Da Silva Xavier G (2018) The Cells of the Islets of Langerhans. J Clin Med 7(3): 54. https://doi.org/10.3390/JCM7030054
  2. Pandiri AR (2014) Overview of exocrine pancreatic pathobiology. Toxicol Pathol 42: 207–216. https://doi.org/10.1177/0192623313509907
  3. Zhou Q, Melton DA (2018) Pancreas regeneration. Nature 557: 351–358. https://doi.org/10.1038/S41586-018-0088-0
  4. Hegyi P, Petersen OH (2013) The exocrine pancreas: the acinar-ductal tango in physiology and pathophysiology. Rev Physiol Biochem Pharmacol 165: 1–30. https://doi.org/10.1007/112_2013_14
  5. Bonner-Weir S, Sullivan BA, Weir GC (2015) Human Islet Morphology Revisited: Human and Rodent Islets Are Not So Different After All. J Histochem Cytochem 63: 604–612. https://doi.org/10.1369/0022155415570969
  6. Dunning BE, Gerich JE (2007) The role of alpha-cell dysregulation in fasting and postprandial hyperglycemia in type 2 diabetes and therapeutic implications. Endocr Rev 28: 253–283. https://doi.org/10.1210/ER.2006-0026
  7. Wierup N, Svensson H, Mulder H, Sundler F (2002) The ghrelin cell: A novel developmentally regulated islet cell in the human pancreas. Regul Pept 107: 63–69. https://doi.org/10.1016/S0167-0115(02)00067-8
  8. Gilbert JM, Adams MT, Sharon N, Jayaraaman H, Blum B (2021) Morphogenesis of the Islets of Langerhans Is Guided by Extraendocrine Slit2 and Slit3 Signals. Mol Cell Biol 41. https://doi.org/10.1128/MCB.00451-20
  9. Guo J, Fu W (2020) Immune regulation of islet homeostasis and adaptation. J Mol Cell Biol 12: 764–774. https://doi.org/10.1093/JMCB/MJAA009
  10. Bertelli E, Bendayan M (2005) Association between endocrine pancreas and ductal system. More than an epiphenomenon of endocrine differentiation and development? J Histochem Cytochem 53: 1071–1086.
  11. Hayden MR, Patel K, Habibi J, Gupta D, Tekwani SS, Whaley-Connell A, Sowers JR (2008) Attenuation of endocrine-exocrine pancreatic communication in type 2 diabetes: pancreatic extracellular matrix ultrastructural abnormalities. J Cardiometab Syndr 3: 234–243. https://doi.org/10.1111/J.1559-4572.2008.00024.X
  12. Suda K, Hosokawa Y, Kuroda J, Yuminamochi T, Ishii Y, Nakazawa K (1994) Pancreatic acinar cells in adult human islets of Langerhans. Pancreas 9: 563–565. https://doi.org/10.1097/00006676-199409000-00004
  13. Murray HE, Paget MB, Bailey CJ, Downing R (2009) Sustained insulin secretory response in human islets co-cultured with pancreatic duct-derived epithelial cells within a rotational cell culture system. Diabetologia 52: 477–485. https://doi.org/10.1007/S00125-008-1247-X
  14. Piciucchi M, Capurso G, Archibugi L, Delle Fave MM, Capasso M, Delle Fave G (2015) Exocrine pancreatic insufficiency in diabetic patients: prevalence, mechanisms, and treatment. Int J Endocrinol 2015: 595–649. https://doi.org/10.1155/2015/595649
  15. Wang TC, Bonner-Weir S, Oates PS, Chulak M, Simon B, Merlino GT, Schmidt EV, Brand SJ (1993) Pancreatic gastrin stimulates islet differentiation of transforming growth factor alpha-induced ductular precursor cells. J Clin Invest 92: 1349–1356. https://doi.org/10.1172/JCI116708
  16. Wang RN, Klöppel G, Bouwens L (1995) Duct- to islet-cell differentiation and islet growth in the pancreas of duct-ligated adult rats. Diabetologia 38: 1405–1411. https://doi.org/10.1007/BF00400600
  17. Deyev IE, Popova NV, Serova OV, Zhenilo SV, Regoli M, Bertelli E, Petrenko AG (2017) Alkaline pH induces IRR-mediated phosphorylation of IRS-1 and actin cytoskeleton remodeling in a pancreatic beta cell line. Biochimie 138. https://doi.org/10.1016/j.biochi.2017.04.002
  18. Serova OV, Gantsova EA, Deyev IE, Petrenko AG (2020) The Value of pH Sensors in Maintaining Homeostasis of the Nervous System. Russ J Bioorg Chem 46: 506–519. https://doi.org/10.1134/S1068162020040196
  19. Masini M, Marselli L, Himpe E, Martino L, Bugliani M, Suleiman M, Boggi U, Filipponi F, Occhipinti M, Bouwens L, De Tata V, Marchetti P (2017) Co-localization of acinar markers and insulin in pancreatic cells of subjects with type 2 diabetes. PLoS One 12. https://doi.org/10.1371/JOURNAL.PONE.0179398
  20. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S (2020) SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 181: 271–280. https://doi.org/10.1016/J.CELL.2020.02.052
  21. Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, Geng Q, Auerbach A, Li F (2020) Structural basis of receptor recognition by SARS-CoV-2. Nature 581: 221–224. https://doi.org/10.1038/S41586-020-2179-Y
  22. Hikmet F, Méar L, Edvinsson Å, Micke P, Uhlén M, Lindskog C (2020) The protein expression profile of ACE2 in human tissues. Mol Syst Biol 16. https://doi.org/10.15252/MSB.20209610
  23. Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H (2004) Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 203: 631–637. https://doi.org/10.1002/PATH.1570
  24. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z (2020) Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 323: 1061–1069. https://doi.org/10.1001/JAMA.2020.1585
  25. Zhan T, Tang Y, Han Z, Zhu Q, Tan J, Liu M, Cai Y, Huang M, Chen X, Cheng X, Deng J, Huang X, Tian X (2021) Clinical Characteristics of 195 Cases of COVID-19 with Gastrointestinal Symptoms COVID-19 with Gastrointestinal Symptoms. Turk J Gastroenterol 32: 148–154. https://doi.org/10.5152/TJG.2021.20379
  26. Schettino M, Pellegrini L, Picascia D, Saibeni S, Bezzio C, Bini F, Omazzi BF, Devani M, Arena I, Bongiovanni M, Manes G, Della Corte CMR (2021) Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms in Northern Italy: A Single-Center Cohort Study. Am J Gastroenterol 116: 306–310. https://doi.org/10.14309/AJG.0000000000000965
  27. Tabesh E, Soheilipour M, Sami R, Mansourian M, Tabesh F, Soltaninejad F, Dehghan M, Nikgoftar N, Gharavinia A, Ghasemi K, Adibi P (2022) Gastrointestinal manifestations in patients with coronavirus disease-2019 (COVID-19): Impact on clinical outcomes. J Res Med Sci 27: 32. https://doi.org/10.4103/JRMS.JRMS_641_21
  28. Bacaksız F, Ebik B, Ekin N, Kılıc J (2021) Pancreatic damage in COVID-19: Why? How? Int J Clin Pract 75. https://doi.org/10.1111/IJCP.14692
  29. Yang F, Xu Y, Dong Y, Huang Y, Fu Y, Li T, Sun C, Pandanaboyana S, Windsor JA, Fu D (2022) Prevalence and prognosis of increased pancreatic enzymes in patients with COVID-19: A systematic review and meta-analysis. Pancreatology 22: 539–546. https://doi.org/10.1016/J.PAN.2022.03.014
  30. Kiyak M, Düzenli T (2022) Lipase elevation on admission predicts worse clinical outcomes in patients with COVID-19. Pancreatology 22: 665–670. https://doi.org/10.1016/J.PAN.2022.04.012
  31. Clausen CL, Leo-Hansen C, Faurholt-Jepsen D, Krogh-Madsen R, Ritz C, Kirk O, Jørgensen HL, Benfield T, Almdal TP, Snorgaard O (2022) Glucometabolic changes influence hospitalization and outcome in patients with COVID-19: An observational cohort study. Diabetes Res Clin Pract 187. https://doi.org/10.1016/J.DIABRES.2022.109880
  32. Dennis JM, Mateen BA, Sonabend R, Thomas NJ, Patel KA, Hattersley AT, Denaxas S, McGovern AP, Vollmer SJ (2021) Type 2 Diabetes and COVID-19-Related Mortality in the Critical Care Setting: A National Cohort Study in England, March-July 2020. Diabetes Care 44: 50–57. https://doi.org/10.2337/DC20-1444
  33. Birabaharan M, Kaelber DC, Pettus JH, Smith DM (2022) Risk of new-onset type 2 diabetes in 600 055 people after COVID-19: A cohort study. Diabetes Obes Metab 24: 1176–1179. https://doi.org/10.1111/DOM.14659
  34. Ambati S, Mihic M, Rosario DC, Sanchez J, Bakar A (2022) New-Onset Type 1 Diabetes in Children With SARS-CoV-2 Infection. Cureus 14. https://doi.org/10.7759/CUREUS.22790
  35. Montefusco L, Ben Nasr M, D’Addio F, Loretelli C, Rossi A, Pastore I, Daniele G, Abdelsalam A, Maestroni A, Dell’Acqua M, Ippolito E, Assi E, Usuelli V, Seelam AJ, Fiorina RM, Chebat E, Morpurgo P, Lunati ME, Bolla AM, Finzi G, Abdi R, Bonventre JV, Rusconi S, Riva A, Corradi D, Santus P, Nebuloni M, Folli F, Zuccotti GV, Galli M, Fiorina P (2021) Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection. Nat Metab 3: 774–785. https://doi.org/10.1038/S42255-021-00407-6
  36. Khunti K, Del Prato S, Mathieu C, Kahn SE, Gabbay RA, Buse JB (2021) COVID-19, Hyperglycemia, and New-Onset Diabetes. Diabetes Care 44: 2645–2655. https://doi.org/10.2337/DC21-1318
  37. Coate KC, Cha J, Shrestha S, Wang W, Gonçalves LM, Almaça J, Kapp ME, Fasolino M, Morgan A, Dai C, Saunders DC, Bottino R, Aramandla R, Jenkins R, Stein R, Kaestner KH, Vahedi G, Brissova M, Powers AC (2020) SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 Are Expressed in the Microvasculature and Ducts of Human Pancreas but Are Not Enriched in β Cells. Cell Metab 32: 1028–1040. https://doi.org/10.1016/J.CMET.2020.11.006
  38. Kusmartseva I, Wu W, Syed F, Van Der Heide V, Jorgensen M, Joseph P, Tang X, Candelario-Jalil E, Yang C, Nick H, Harbert JL, Posgai AL, Paulsen JD, Lloyd R, Cechin S, Pugliese A, Campbell-Thompson M, Vander Heide RS, Evans-Molina C, Homann D, Atkinson MA (2020) Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19. Cell Metab 32: 1041–1051. https://doi.org/10.1016/J.CMET.2020.11.005
  39. Fignani D, Licata G, Brusco N, Nigi L, Grieco GE, Marselli L, Overbergh L, Gysemans C, Colli ML, Marchetti P, Mathieu C, Eizirik DL, Sebastiani G, Dotta F (2020) SARS-CoV-2 Receptor Angiotensin I-Converting Enzyme Type 2 (ACE2) Is Expressed in Human Pancreatic β-Cells and in the Human Pancreas Microvasculature. Front Endocrinol (Lausanne) 11. https://doi.org/10.3389/FENDO.2020.596898
  40. Müller JA, Groß R, Conzelmann C, Krüger J, Merle U, Steinhart J, Weil T, Koepke L, Bozzo CP, Read C, Fois G, Eiseler T, Gehrmann J, van Vuuren J, Wessbecher IM, Frick M, Costa IG, Breunig M, Grüner B, Peters L, Schuster M, Liebau S, Seufferlein T, Stenger S, Stenzinger A, MacDonald PE, Kirchhoff F, Sparrer KMJ, Walther P, Lickert H, Barth TFE, Wagner M, Münch J, Heller S, Kleger A (2021) SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. Nat Metab 3: 149–165. https://doi.org/10.1038/S42255-021-00347-1
  41. Steenblock C, Richter S, Berger I, Barovic M, Schmid J, Schubert U, Jarzebska N, von Mässenhausen A, Linkermann A, Schürmann A, Pablik J, Dienemann T, Evert K, Rodionov RN, Semenova NY, Zinserling VA, Gainetdinov RR, Baretton G, Lindemann D, Solimena M, Ludwig B, Bornstein SR (2021) Viral infiltration of pancreatic islets in patients with COVID-19. Nat Commun 12. https://doi.org/10.1038/S41467-021-23886-3
  42. Cantuti-Castelvetri L, Ojha R, Pedro LD, Djannatian M, Franz J, Kuivanen S, van der Meer F, Kallio K, Kaya T, Anastasina M, Smura T, Levanov L, Szirovicza L, Tobi A, Kallio-Kokko H, Österlund P, Joensuu M, Meunier FA, Butcher SJ, Winkler MS, Mollenhauer B, Helenius A, Gokce O, Teesalu T, Hepojoki J, Vapalahti O, Stadelmann C, Balistreri G, Simons M (2020) Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science 370. https://doi.org/10.1126/SCIENCE.ABD2985
  43. Wu CT, Lidsky PV, Xiao Y, Lee IT, Cheng R, Nakayama T, Jiang S, Demeter J, Bevacqua RJ, Chang CA, Whitener RL, Stalder AK, Zhu B, Chen H, Goltsev Y, Tzankov A, Nayak JV, Nolan GP, Matter MS, Andino R, Jackson PK (2021) SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment. Cell Metab 33: 1565–1576. https://doi.org/10.1016/J.CMET.2021.05.013
  44. Tang X, Uhl S, Zhang T, Xue D, Li B, Vandana JJ, Acklin JA, Bonnycastle LL, Narisu N, Erdos MR, Bram Y, Chandar V, Chong ACN, Lacko LA, Min Z, Lim JK, Borczuk AC, Xiang J, Naji A, Collins FS, Evans T, Liu C, tenOever BR, Schwartz RE, Chen S (2021) SARS-CoV-2 infection induces beta cell transdifferentiation. Cell Metab 33: 1577–1591. https://doi.org/10.1016/J.CMET.2021.05.015
  45. Xie Y, Al-Aly Z (2022) Risks and burdens of incident diabetes in long COVID: a cohort study. Lancet Diabetes Endocrinol 10: 311–321. https://doi.org/10.1016/S2213-8587(22)00044-4
  46. Steenblock C, Hassanein M, Khan EG, Yaman M, Kamel M, Barbir M, Lorke DE, Rock JA, Everett D, Bejtullah S, Heimerer A, Tahirukaj E, Beqiri P, Bornstein SR (2022) Diabetes and COVID-19: Short- and Long-Term Consequences. Horm Metab Res 54: 503–509. https://doi.org/10.1055/A-1878-9566
  47. Mittal J, Ghosh A, Bhatt SP, Anoop S, Ansari IA, Misra A (2021) High prevalence of post COVID-19 fatigue in patients with type 2 diabetes: A case-control study. Diabetes Metab Syndr 15. https://doi.org/10.1016/J.DSX.2021.102302

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Endocrine and exocrine parts of the pancreas. The anatomy of the pancreas includes both exocrine and endocrine parts: Exocrine cells secrete digestive enzymes and pancreatic juice into the small intestine, and endocrine cells secrete hormones such as insulin and glucagon into the bloodstream to regulate blood sugar levels. This dual function of the pancreas is necessary to maintain optimal metabolism and proper digestion in the body.

Download (184KB)
Indexing metadata
3. Fig. 2. Mechanisms of interaction of islets of Langerhans, duct cells and acinuses. While exocrine cells secrete pancreatic juice along with enzymes into the small intestine, endocrine cells secrete hormones such as insulin and glucagon into the bloodstream. These hormones are vital for regulating blood sugar levels and work in coordination with digestive enzymes produced by exocrine cells to ensure proper digestion and absorption of nutrients. The interaction of these parts with each other ensures the regulation of these processes.

Download (191KB)
Indexing metadata

Copyright (c) 2024 Russian Academy of Sciences