Glucose Homeostasis Dependency on Acini-islet-acinar (AIA) Axis Communication: a New Possible Pathophysiological Hypothesis Regarding Diabetes Mellitus

Overview

Journal Nutr Diabetes

Specialties Endocrinology
Nutritional Sciences

Date 2018 Oct 9

PMID 30293998

Citations 16

Authors

Stefan G Pierzynowski

Peter C Gregory

Rafal Filip

Jaroslaw Wolinski

Kateryna Goncharova Pierzynowska

Affiliations

Soon will be listed here.

Abstract

Studies have highlighted the existence of two intra-pancreatic axes of communication: one involved in the regulation of enzyme production by insulin-the insular-acinar axis; and another involved in the regulation of insulin release by pancreatic enzymes-the acini-insular axis. Previous studies by our laboratory show that pancreatic enzymes can affect blood glucose homeostasis and insulin secretion independently of their digestive functions, both from the gut lumen and probably from the blood. As a result we would like to introduce here the concept of acini-islet-acinar (AIA) axis communication (feedback), which could play an important role in the development of obesity and diabetes type 2. The AIA feedback links the endocrine and exocrine parts of the pancreas and emphasizes the essential role that the pancreas plays, as a single organ, in the regulation of glucose homeostasis by amylase most probably in gut epithelium and by insulin and glucagon in peripheral blood.

Citing Articles

The Regulatory Role of Pancreatic Enzymes in the Maintenance of Small Intestinal Structure and Enterocyte Turnover with Special Reference to Alpha Amylase.

Zaworski K, Wychowanski P, Szkopek D, Wolinski J, Donaldson J, Pierzynowski S Int J Mol Sci. 2025; 26(1.

PMID: 39796104 PMC: 11719925. DOI: 10.3390/ijms26010249.

Amylase intrapancreatic infusion delays insulin release during an intravenous glucose tolerance test, proof of acini-islet-acinar interactions.

Pierzynowska K, Wychowanski P, Zaworski K, Wolinski J, Donaldson J, Szkopek D World J Exp Med. 2024; 14(3):92589.

PMID: 39312707 PMC: 11372737. DOI: 10.5493/wjem.v14.i3.92589.

A review: Pancreatic enzymes in the treatment of chronic pancreatic insufficiency in companion animals.

Szkopek D, Pierzynowski S, Pierzynowska K, Zaworski K, Kondej A, Wychowanski P J Vet Intern Med. 2024; 38(4):2026-2033.

PMID: 38721836 PMC: 11256127. DOI: 10.1111/jvim.17096.

Mechanisms of spinophilin-dependent pancreas dysregulation in obesity.

Stickel K, Shah N, Claeboe E, Orr K, Mosley A, Doud E Am J Physiol Endocrinol Metab. 2024; 327(2):E155-E171.

PMID: 38630048 PMC: 11427100. DOI: 10.1152/ajpendo.00099.2023.

ECM-derived biomaterials for regulating tissue multicellularity and maturation.

Smandri A, Al-Masawa M, Hwei N, Fauzi M iScience. 2024; 27(3):109141.

PMID: 38405613 PMC: 10884934. DOI: 10.1016/j.isci.2024.109141.

References

Stearns A, Balakrishnan A, Tavakkolizadeh A . Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport. Am J Physiol Gastrointest Liver Physiol. 2010; 297(5):G950-7. PMC: 2777457. DOI: 10.1152/ajpgi.00253.2009. View

Pierzynowski S, Westrom B, Svendsen J, Svendsen L, Karlsson B . Development and regulation of porcine pancreatic function. Int J Pancreatol. 1995; 18(2):81-94. DOI: 10.1007/BF02785881. View

Bank S, Marks I, Vinik A . Clinical and hormonal aspects of pancreatic diabetes. Am J Gastroenterol. 1975; 64(1):13-22. View

Borbely Y, Plebani A, Kroll D, Ghisla S, Nett P . Exocrine Pancreatic Insufficiency after Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2016; 12(4):790-794. DOI: 10.1016/j.soard.2015.10.084. View

Lund A, Bagger J, Christensen M, Knop F, Vilsboll T . Glucagon and type 2 diabetes: the return of the alpha cell. Curr Diab Rep. 2014; 14(12):555. DOI: 10.1007/s11892-014-0555-4. View

Teichmann J, Riemann J, Lange U . Prevalence of exocrine pancreatic insufficiency in women with obesity syndrome: assessment by pancreatic fecal elastase 1. ISRN Gastroenterol. 2011; 2011:951686. PMC: 3216381. DOI: 10.5402/2011/951686. View

Kanno T, Saito A . The potentiating influences of insulin on pancreozymin-induced hyperpolarization and amylase release in the pancreatic acinar cell. J Physiol. 1976; 261(3):505-21. PMC: 1309157. DOI: 10.1113/jphysiol.1976.sp011571. View

van Dam R, Seidell J . Carbohydrate intake and obesity. Eur J Clin Nutr. 2008; 61 Suppl 1:S75-99. DOI: 10.1038/sj.ejcn.1602939. View

Bueno L, Fioramonti J . Protease-activated receptor 2 and gut permeability: a review. Neurogastroenterol Motil. 2008; 20(6):580-7. DOI: 10.1111/j.1365-2982.2008.01139.x. View

10.

Halbrook C, Wen H, Ruggeri J, Takeuchi K, Zhang Y, Pasca di Magliano M . Mitogen-activated Protein Kinase Kinase Activity Maintains Acinar-to-Ductal Metaplasia and Is Required for Organ Regeneration in Pancreatitis. Cell Mol Gastroenterol Hepatol. 2017; 3(1):99-118. PMC: 5235341. DOI: 10.1016/j.jcmgh.2016.09.009. View

11.

Henderson J, Daniel P, Fraser P . The pancreas as a single organ: the influence of the endocrine upon the exocrine part of the gland. Gut. 1981; 22(2):158-67. PMC: 1419227. DOI: 10.1136/gut.22.2.158. View

12.

Ronaghan N, Shang J, Iablokov V, Zaheer R, Colarusso P, Dion S . The serine protease-mediated increase in intestinal epithelial barrier function is dependent on occludin and requires an intact tight junction. Am J Physiol Gastrointest Liver Physiol. 2016; 311(3):G466-79. PMC: 5076006. DOI: 10.1152/ajpgi.00441.2015. View

13.

Pierzynowski S, Westrom B, Erlanson-Albertsson C, Ahren B, Svendsen J, Karlsson B . Induction of exocrine pancreas maturation at weaning in young developing pigs. J Pediatr Gastroenterol Nutr. 1993; 16(3):287-93. DOI: 10.1097/00005176-199304000-00012. View

14.

Prykhodko O, Pierzynowski S, Nikpey E, Sureda E, Fedkiv O, Westrom B . Pancreatic and pancreatic-like microbial proteases accelerate gut maturation in neonatal rats. PLoS One. 2015; 10(2):e0116947. PMC: 4319746. DOI: 10.1371/journal.pone.0116947. View

15.

Viljakainen H, Andersson-Assarsson J, Armenio M, Pekkinen M, Pettersson M, Valta H . Low Copy Number of the AMY1 Locus Is Associated with Early-Onset Female Obesity in Finland. PLoS One. 2015; 10(7):e0131883. PMC: 4489572. DOI: 10.1371/journal.pone.0131883. View

16.

Posho L, Morel M, Bernard F, Blachier F, Meslin J, Duee P . Glucose, galactose, and glutamine metabolism in pig isolated enterocytes during development. Pediatr Res. 1994; 36(2):175-81. DOI: 10.1203/00006450-199408000-00007. View

17.

Couture Y, Dunnigan J, Morisset . Stimulation of pancreatic amylase secretion and protein synthesis by insulin. Scand J Gastroenterol. 1972; 7(3):257-63. DOI: 10.3109/00365527209181162. View

18.

Lozinska L, Westrom B, Prykhodko O, Lindqvist A, Wierup N, Ahren B . Decreased insulin secretion and glucose clearance in exocrine pancreas-insufficient pigs. Exp Physiol. 2015; 101(1):100-12. DOI: 10.1113/EP085431. View

19.

Lemper M, Leuckx G, Heremans Y, German M, Heimberg H, Bouwens L . Reprogramming of human pancreatic exocrine cells to β-like cells. Cell Death Differ. 2014; 22(7):1117-30. PMC: 4572860. DOI: 10.1038/cdd.2014.193. View

20.

Sheikh S, Gudipaty L, De Leon D, Hadjiliadis D, Kubrak C, Rosenfeld N . Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance. Diabetes. 2016; 66(1):134-144. PMC: 5204312. DOI: 10.2337/db16-0394. View