Pathologic pancreatic endocrine cell hyperplasia

Ouyang, Debra; Dhall, Deepti; Yu, Run

doi:10.3748/wjg.v17.i2.137

Cited by 49 publications

(29 citation statements)

References 62 publications

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“…ACH is defined as an overwhelming and specific increase of pancreatic α cell numbers [8,19] . Based on etiology and glucagon levels, 3 types of ACH are observed.…”

Section: Pancreatic Achmentioning

confidence: 99%

“…Neuroendocrine tumors in the gastrointestinal tract and pancreas (GEP-NETs) are relatively rare and indolent tumors with variable biological behaviors [4][5][6] . GEP-NETs can also be derived from precursor lesions [7][8][9] . In atrophic gastritis, hypergastrinemia drives enterochromaffin-like cell hyperplasia, which in turn can give rise to gastric carcinoids [7,10] .…”

Section: Introductionmentioning

confidence: 99%

“…In the pancreata of patients with MEN1 and mice with heterozygous MEN1 inactivation, the hyperplastic endocrine cells are polyclonal and multihormonal and contain the normal menin allele, while microadenomas have to first lose the normal menin allele [17,18] . In contrast, uni-hormonal pancreatic endocrine cell hyperplasia such as pancreatic α cell hyperplasia (ACH) and pancreatic polypeptide cell hyperplasia has only been recognized in the last several years [8,9,19] . Although pancreatic polypeptide cell hyperplasia may be a physiological variation of normal pancreatic polypeptide cell distribution, ACH is clearly a pathologic precursor lesion leading to PNET pathogenesis [19] .…”

Section: Introductionmentioning

confidence: 99%

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Elusive liver factor that causes pancreatic α cell hyperplasia: A review of literature

Zheng

Lucas

et al. 2015

WJGP

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Tumors and cancers of the gastrointestinal tract and pancreas are commonly derived from precursor lesions so that understanding the physiological, cellular, and molecular mechanisms underlying the pathogenesis of precursor lesions is critical for the prevention and treatment of those neoplasms. Pancreatic neuroendocrine tumors (PNETs) can also be derived from precursor lesions. Pancreatic α cell hyperplasia (ACH), a specific and overwhelming increase in the number of α cells, is a precursor lesion leading to PNET pathogenesis. One of the 3 subtypes of ACH, reactive ACH is caused by glucagon signaling disruption and invariably evolves into PNETs. In this article, the existing work on the mechanisms underlying reactive ACH pathogenesis is reviewed. It is clear that the liver secretes a humoral factor regulating α cell numbers but the identity of the liver factor remains elusive. Potential approaches to identify the liver factor are discussed. lesions. One of the precursor lesions, reactive pancreatic α cell hyperplasia is caused by glucagon signaling disruption and invariably evolves into pancreatic neuroendocrine tumors. In this article, the existing work on the mechanisms underlying the novel precursor lesion is reviewed. It is clear that the liver secretes a humoral factor regulating pancreatic α cell numbers but the identity of the liver factor remains elusive. Potential approaches to identify the liver factor are discussed.Yu R, Zheng Y, Lucas MB, Tong YG. Elusive liver factor that causes pancreatic α cell hyperplasia: A review of literature. World J Gastrointest Pathophysiol 2015; 6(4): 131-139 Available from:

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“…ACH is defined as an overwhelming and specific increase of pancreatic α cell numbers [8,19] . Based on etiology and glucagon levels, 3 types of ACH are observed.…”

Section: Pancreatic Achmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Elusive liver factor that causes pancreatic α cell hyperplasia: A review of literature

Zheng

Lucas

et al. 2015

WJGP

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“…The above heterogeneity confirms that histological finding need not always correspond with hormonal activity and clinical symptoms. In addition, beta cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy, caused by mutations in the islet ATPsensitive potassium channel, and to non-insulinoma pancreatogenous hypoglycemia in adults (Ouyang et al, 2011). Insulinoma is usually localized within the pancreas, extrapancreatic tumors (e.g.…”

Section: Epidemiology and Basic Characteristicsmentioning

confidence: 99%

Insulinoma – Diagnosis and Treatment

Škrha¹,

Dušková²,

Sváb³

et al. 2011

Hypoglycemia - Causes and Occurrences

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“…In those mice, a-cell hyperplasia is evident at 3 months, followed by islet dysplasia at 6-7 months, and pancreatic neuroendocrine tumors with 100% penetrance at 10-12 months. As a-cell hyperplasia also occurs in animal models with deficiency of prohormone convertase 2 (resulting in failure to produce glucagon) or treated with GCGR antagonists (Furuta et al 1997, Petersen & Sullivan 2001, Qureshi et al 2004, Winzell et al 2007, it is likely that glucagon regulates its own production by negative feedback, the removal of which by GCGR inactivating mutation or deletion causes compensatory hyperglucagonemia and a-cell hyperplasia, a precursor to neuroendocrine tumors (Ouyang et al 2011, Yu et al 2011b.…”

Section: Introductionmentioning

confidence: 99%

Rescue of a pathogenic mutant human glucagon receptor by pharmacological chaperones

Yu¹,

Chen²,

Liu³

et al. 2012

Journal of Molecular Endocrinology

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We have previously demonstrated that a homozygous inactivating P86S mutation of the glucagon receptor (GCGR) causes a novel human disease of hyperglucagonemia, pancreatic a-cell hyperplasia, and pancreatic neuroendocrine tumors (Mahvash disease). The mechanisms for the decreased activity of the P86S mutant (P86S) are abnormal receptor localization to the endoplasmic reticulum (ER) and defective interaction with glucagon. To search for targeted therapies for Mahvash disease, we examined whether P86S can be trafficked to the plasma membrane by pharmacological chaperones and whether novel glucagon analogs restore effective receptor interaction. We used enhanced green fluorescent protein-tagged P86S stably expressed in HEK 293 cells to allow fluorescence imaging and western blotting and molecular modeling to design novel glucagon analogs in which alanine 19 was replaced with serine or asparagine. Incubation at 27 8C largely restored normal plasma membrane localization and normal processing of P86S but osmotic chaperones had no effects. The ER stressors thapsigargin and curcumin partially rescued P86S. The lipophilic GCGR antagonist L-168,049 also partially rescued P86S, so did Cpd 13 and 15 to a smaller degree. The rescued P86S led to more glucagon-stimulated cAMP production and was internalized by glucagon. Compared with the native glucagon, the novel glucagon analogs failed to stimulate more cAMP production by P86S. We conclude that the mutant GCGR is partially rescued by several pharmacological chaperones and our data provide proof-of-principle evidence that Mahvash disease can be potentially treated with pharmacological chaperones. The novel glucagon analogs, however, failed to interact with P86S more effectively.

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Pathologic pancreatic endocrine cell hyperplasia

Cited by 49 publications

References 62 publications

Elusive liver factor that causes pancreatic α cell hyperplasia: A review of literature

Elusive liver factor that causes pancreatic α cell hyperplasia: A review of literature

Insulinoma – Diagnosis and Treatment

Rescue of a pathogenic mutant human glucagon receptor by pharmacological chaperones

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