Nesidioblastosis of the pancreas: definition of the syndrome and the management of the severe neonatal hyperinsulinaemic hypoglycaemia.

Aynsley-Green, A; Polak, J.M.; Bloom, S R; Gough, Martin; Keeling, Jean W.; Ashcroft, S. J. H.; Turner, R. C.; Baum, J D

doi:10.1136/adc.56.7.496

Cited by 206 publications

(111 citation statements)

References 45 publications

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“…Loss of function of the pancreatic islet K ATP channel, because of mutation of either the SUR1 or Kir6.2 subunit (11)(12)(13)(14), has been demonstrated to lead to persistent hyperinsulinemic hypoglycemia of infancy, an autosomal recessive disorder characterized by unregulated insulin secretion and severe hypoglycemia (15). Disease phenotypes have not yet been assigned to the other K ATP channels.…”

Section: Atp-sensitive Potassium (K Atp )mentioning

confidence: 99%

A Novel Sulfonylurea Receptor Family Member Expressed in the Embryonic Drosophila Dorsal Vessel and Tracheal System

Nasonkin¹,

Alikaşifoğlu²,

Ambrose³

et al. 1999

Journal of Biological Chemistry

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Sulfonylurea receptors (SURx) are required subunits of the ATP-sensitive potassium channel. SURx alone is electrophysiologically inert. However, when SURx is combined with an inward rectifier Kir6.2 subunit, ATPsensitive potassium channel activity is generated. We report the identification, characterization, and localization of Dsur, a novel Drosophila gene that is highly related to the vertebrate SUR family. The Dsur coding sequence contains structural features characteristic of the ABC transporter family and, in addition, harbors 1.7 kilobases of a distinctive sequence that does not share homology with any known gene. When Dsur alone is expressed in Xenopus oocytes glibenclamide-sensitive potassium channel activity occurs. During Drosophila embryogenesis, the Dsur gene is specifically expressed in the developing tracheal system and dorsal vessel. Studies of the Drosophila genome support that only a single Dsur gene is present. Our data reveal conservation of glibenclamide-sensitive potassium channels in Drosophila and suggest that Dsur may play an important role during Drosophila embryogenesis. The lack of gene duplication in the Drosophila system provides a unique opportunity for functional studies of SUR using a genetic approach.

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Section: Atp-sensitive Potassium (K Atp )mentioning

confidence: 99%

A Novel Sulfonylurea Receptor Family Member Expressed in the Embryonic Drosophila Dorsal Vessel and Tracheal System

Nasonkin¹,

Alikaşifoğlu²,

Ambrose³

et al. 1999

Journal of Biological Chemistry

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“…Congenital HI, characterized by dysregulated insulin secretion [12], is the most common cause of persistent and recurrent hypoglycaemia in infancy. The typical incidence is estimated to be about 1 : 50 000 live births but can be as high as 1 : 3000 in areas of high consanguinity [15].…”

Section: Congenital Hi: Hyperexcitability and Hypersecretionmentioning

confidence: 99%

β‐cell hyperexcitability: from hyperinsulinism to diabetes

Nichols

Koster

Remedi

2007

Diabetes Obesity Metabolism

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Nutrient oxidation in b cells generates a rise in [ATP]: [ADP] ratio. This reduces K ATP channel activity, leading to depolarization, activation of voltage-dependent Ca 2þ channels, Ca 2þ entry and insulin secretion. Consistent with this paradigm, loss-of-function mutations in the genes (KCNJ11 and ABCC8) that encode the two subunits (Kir6.2 and SUR1, respectively) of the ATP-sensitive K þ (K ATP ) channel underlie hyperinsulinism in humans, a genetic disorder characterized by dysregulated insulin secretion. In mice with genetic suppression of K ATP channel subunit expression, partial loss of K ATP channel conductance also causes hypersecretion, but unexpectedly, complete loss results in an undersecreting, mildly glucose-intolerant phenotype. When challenged by a high-fat diet, normal mice and mice with reduced K ATP channel density respond with hypersecretion, but mice with more significant or complete loss of K ATP channels cross over, or progress further, to an undersecreting, diabetic phenotype. It is our contention that in mice, and perhaps in humans, there is an inverse U-shaped response to hyperexcitabilty, leading first to hypersecretion but with further exacerbation to undersecretion and diabetes. The causes of the overcompensation and diabetic susceptibility are poorly understood but may have broader implications for the progression of hyperinsulinism and type 2 diabetes in humans.

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“…The histologic features were first associated with severe hypoglycemia in infants. [7][8][9] In recent years, a number of genes including SUR1, Kir6.2, GCK, GLUD1, and short-chain 3-hydroxyacyl CoA dehydrogenase have been identified in infantile nesidioblastosis. [10][11][12] An association with Beckwith-Weideman syndrome has also been identified.…”

mentioning

confidence: 99%

Hyperinsulinemic hypoglycemia with nesidioblastosis: histologic features and growth factor expression

et al. 2009

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Hypoglycemia secondary to nesidioblastosis is rare in adults, and the pathogenesis of this condition is unknown. To determine factors leading to nesidioblastosis in adults, we analyzed 36 cases of nesidioblastosis including 27 cases of postgastric bypass nesidioblastosis and 9 cases of idiopathic nesidioblastosis in adults by immunohistochemistry using antibodies to insulin-like growth factor1, insulin-like growth factor2 (IGF2), insulin-like growth factor one receptor-a epidermal growth factor receptor, transforming growth factor-b1 and 2, and transforming growth factor-b receptor type 3. Fifty-two surgically excised pancreatic specimens from patients with benign exocrine tumors and no evidence of hypoglycemia were used as controls. There was increased IGF2, insulin-like growth factor receptor1 receptor-a and transforming growth factor-b receptor 3 expression in islets from nesidioblastosis patients compared to controls. Peliosis-type vascular ectasia was more common in nesidioblastosis patients compared to controls. These findings suggest that increased production of growth factors and growth factor receptors may contribute to the development of nesidioblastosis in adults.

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Nesidioblastosis of the pancreas: definition of the syndrome and the management of the severe neonatal hyperinsulinaemic hypoglycaemia.

Cited by 206 publications

References 45 publications

A Novel Sulfonylurea Receptor Family Member Expressed in the Embryonic Drosophila Dorsal Vessel and Tracheal System

A Novel Sulfonylurea Receptor Family Member Expressed in the Embryonic Drosophila Dorsal Vessel and Tracheal System

β‐cell hyperexcitability: from hyperinsulinism to diabetes

Hyperinsulinemic hypoglycemia with nesidioblastosis: histologic features and growth factor expression

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