Alpha cell hyperplasia

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Alpha cell hyperplasia
SpecialtyGastroenterology

Alpha cell hyperplasia is defined as a specific (without similar change in other islet cells), diffuse (not limited to a particular part of pancreas), and overwhelming (many-fold) increase of the number of pancreatic alpha cells.[1][2] The pancreatic islets normally contain 4 types of cells; the alpha cells produce and release glucagon, a hormone that regulates the metabolism of glucose and amino acids. Although first described in early 1990s, alpha cell hyperplasia had remained an esoteric topic until the mid-2010s. Based on the pathogenesis and clinical presentation, alpha cell hyperplasia can be divided into 3 types: reactive, nonfunctional, and functional.

Reactive alpha cell hyperplasia[edit]

Any means to inhibit normal glucagon signaling in any vertebrate animals tested so far (zebra fish, mice, monkeys, and humans) causes reactive alpha cell hyperplasia.[2][3][4][5][6][7][8] There is a negative feedback loop linking the pancreatic alpha cells and the liver.[9][10] When glucagon signaling is inhibited, the liver (the main target organ of glucagon) releases excess amounts of amino acids into the circulation (hyperaminoacidemia) which stimulate the alpha cells to proliferate and to produce and release more glucagon.[11] Humans and animals with reactive alpha cell hyperplasia do not exhibit signs of glucagon excess as their glucagon signaling is inhibited at the first place. Reactive alpha cell hyperplasia is a preneoplastic lesion. Humans with inactivating glucagon mutations (i.e. Mahvash disease) and several murine models of reactive alpha cell hyperplasia all eventually develop pancreatic neuroendocrine tumors.[9][12][6][13]

Nonfunctional alpha cell hyperplasia[edit]

Nonfunctional and reactive alpha cell hyperplasia are indistinguishable histologically. Nonfunctional alpha cell hyperplasia, however, is not associated with hyperglucagonemia.[14][15] The cause of nonfunctional alpha cell hyperplasia in humans requires further investigation. Nonfunctional alpha cell hyperplasia is also a preneoplastic lesion.

Functional alpha cell hyperplasia[edit]

Functional alpha cell hyperplasia differs from reactive and nonfunctional alpha cell hyperplasia in that the functional alpha cell hyperplasia is associated with hyperglucagonemia and the hyperglucagonemia results in glucagonoma syndrome.[16] Functional alpha cell hyperplasia is poorly characterized so far.

See also[edit]

References[edit]

  1. ^ Ouyang D, Dhall D, Yu R (2011). "Pathologic pancreatic endocrine cell hyperplasia". World Journal of Gastroenterology. 17 (2): 137–43. doi:10.3748/wjg.v17.i2.137. PMC 3020366. PMID 21245985.
  2. ^ a b Yu R (2014). "Pancreatic α-cell hyperplasia: facts and myths". Journal of Clinical Endocrinology and Metabolism. 99 (3): 748–56. doi:10.1210/jc.2013-2952. PMID 24285676.
  3. ^ Li M, Dean ED, Zhao L, Nicholson WE, Powers AC, Chen W (2015). "Glucagon receptor inactivation leads to α-cell hyperplasia in zebrafish". Journal of Endocrinology. 227 (2): 93–103. doi:10.1530/JOE-15-0284. PMC 4598637. PMID 26446275.
  4. ^ Parker JC, Andrews KM, Allen MR, Stock JL, McNeish JD (2002). "Glycemic control in mice with targeted disruption of the glucagon receptor gene". Biochemical and Biophysical Research Communications. 290 (2): 839–43. doi:10.1006/bbrc.2001.6265. PMID 11785978.
  5. ^ Hayashi Y, Yamamoto M, Mizoguchi H, Watanabe C, Ito R, Yamamoto S, Sun XY, Murata Y (2009). "Mice deficient for glucagon gene-derived peptides display normoglycemia and hyperplasia of islet alpha-cells but not of intestinal L-cells". Molecular Endocrinology. 23 (12): 1990–9. doi:10.1210/me.2009-0296. PMC 5419124. PMID 19819987.
  6. ^ a b Jones HB, Reens J, Brocklehurst SR, Betts CJ, Bickerton S, Bigley AL, Jenkins RP, Whalley NM, Morgan D, Smith DM (1999). "Islets of Langerhans from prohormone convertase-2 knockout mice show α-cell hyperplasia and tumorigenesis with elevated α-cell neogenesis". International Journal of Experimental Pathology. 95 (1): 29–48. doi:10.1111/iep.12066. PMC 3919648. PMID 24456331.
  7. ^ Yan H, Gu W, Yang J, Bi V, Shen Y, Lee E, Winters KA, Komorowski R, Zhang C, Patel JJ, Caughey D, Elliott GS, Lau YY, Wang J, Li YS, Boone T, Lindberg RA, Hu S, Véniant MM (2009). "Fully human monoclonal antibodies antagonizing the glucagon receptor improve glucose homeostasis in mice and monkeys". Journal of Pharmacology and Experimental Therapeutics. 329 (1): 102–11. doi:10.1124/jpet.108.147009. PMID 19129372. S2CID 6569082.
  8. ^ Zhou C, Dhall D, Nissen NN, Chen CR, Yu R (1999). "Homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor". Pancreas. 38 (8): 941–6. doi:10.1097/MPA.0b013e3181b2bb03. PMC 2767399. PMID 19657311.
  9. ^ a b Yu R, Zheng Y, Lucas MB, Tong YG (2015). "Elusive liver factor that causes pancreatic α cell hyperplasia: A review of literature". World Journal of Gastrointestinal Pathophysiology. 6 (4): 131–9. doi:10.4291/wjgp.v6.i4.131. PMC 4644877. PMID 26600971.
  10. ^ Holst JJ, Wewer Albrechtsen NJ, Pedersen J, Knop FK (2017). "Glucagon and amino acids are linked in a mutual feedback cycle: the liver-α-cell axis". Diabetes. 66 (2): 235–40. doi:10.2337/db16-0994. PMID 28108603.
  11. ^ Solloway MJ, Madjidi A, Gu C, Eastham-Anderson J, Clarke HJ, Kljavin N, Zavala-Solorio J, Kates L, Friedman B, Brauer M, Wang J, Fiehn O, Kolumam G, Stern H, Lowe JB, Peterson AS, Allan BB (2015). "Glucagon couples hepatic amino acid catabolism to mTOR-dependent regulation of α-cell mass". Cell Reports. 12 (3): 495–510. doi:10.1016/j.celrep.2015.06.034. PMID 26166562.
  12. ^ Yu R, Dhall D, Nissen NN, Zhou C, Ren SG (2011). "Pancreatic neuroendocrine tumors in glucagon receptor-deficient mice". PLOS ONE. 6 (8): e23397. Bibcode:2011PLoSO...623397Y. doi:10.1371/journal.pone.0023397. PMC 3154424. PMID 21853126.
  13. ^ Takano Y, Kasai K, Takagishi Y, Kikumori T, Imai T, Murata Y, Hayashi Y (2015). "Pancreatic Neuroendocrine Tumors in Mice Deficient in Proglucagon-Derived Peptides". PLOS ONE. 10 (7): e0133812. Bibcode:2015PLoSO..1033812T. doi:10.1371/journal.pone.0133812. PMC 4508046. PMID 26192435.
  14. ^ Al-Sarireh B, Haidermota M, Verbeke C, Rees DA, Yu R, Griffiths AP (2013). "Glucagon cell adenomatosis without glucagon receptor mutation". Pancreas. 42 (2): 360–2. doi:10.1097/MPA.0b013e31825b6acd. PMID 23407487.
  15. ^ Sipos B, Sperveslage J, Anlauf M, Hoffmeister M, Henopp T, Buch S, Hampe J, Weber A, Hammel P, Couvelard A, Höbling W, Lieb W, Boehm BO, Klöppel G (2015). "Glucagon cell hyperplasia and neoplasia with and without glucagon receptor mutations". Journal of Clinical Endocrinology and Metabolism. 100 (5): E783–8. doi:10.1210/jc.2014-4405. PMID 25695890.
  16. ^ Otto AI, Marschalko M, Zalatnai A, Toth M, Kovacs J, Harsing J, Tulassay Z, Karpati S (2011). "Glucagon cell adenomatosis: a new entity associated with necrolytic migratory erythema and glucagonoma syndrome". Journal of the American Academy of Dermatology. 65 (2): 458–9. doi:10.1016/j.jaad.2010.04.010. PMID 21763589.
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