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MeSH Review:

Persistent Hyperinsulinemia Hypoglycemia of Infancy

Lin, Y.W., Thornton, P.S., Kelly, A., Hussain, K., Kelly, A., et al.

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Disease relevance of Persistent Hyperinsulinemia Hypoglycemia of Infancy

Serum glucagon counterregulatory hormonal response to hypoglycemia is blunted in congenital hyperinsulinism [1].
The recent identification of a novel form of congenital hyperinsulinism associated with asymptomatic hyperammonemia assigns glutamate oxidation by glutamate dehydrogenase a more important role than previously recognized in beta-cell insulin secretion and hepatic and CNS ammonia detoxification [2].
We report the case of a newborn infant affected by congenital hyperinsulinism who developed cholelithiasis associated with cholestatic jaundice following treatment with octreotide, a somatostatin analogue [3].

High impact information on Persistent Hyperinsulinemia Hypoglycemia of Infancy

INTERPRETATION: Heterozygous E1506K substitution in the SUR1 gene causes congenital hyperinsulinism in infancy, loss of insulin secretory capacity in early adulthood, and diabetes in middle-age [4].
A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels [5].
Our findings reveal a novel molecular mechanism for loss of KATP channel function and congenital hyperinsulinism and support the importance of phospholipids and/or long chain acyl-CoAs in setting the physiological activity of beta-cell KATP channels [5].
In conclusion, the loss of ATP-sensitive K(+) channels and or elevated intraislet insulin cannot explain the blunted glucagon release in all patients with congenital hyperinsulinism [1].
Identification of regulatory mutations of glutamate dehydrogenase (GDH) in a form of congenital hyperinsulinism (GDH-HI) is providing a model for basal insulin secretion (IS) and amino acid (AA)-stimulated insulin secretion (AASIS) in which glutaminolysis plays a key role [6].

Chemical compound and disease context of Persistent Hyperinsulinemia Hypoglycemia of Infancy

Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes [7].
Severe congenital hyperinsulinism caused by a mutation in the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium channel impairing trafficking and function [8].
Acute insulin responses to calcium and tolbutamide do not differentiate focal from diffuse congenital hyperinsulinism [9].
Short- and long-term use of octreotide in the treatment of congenital hyperinsulinism [10].
While the long-term effects of growth remain undetermined, current findings suggest octreotide may provide a reasonable addition or alternative to diazoxide in controlling symptoms of congenital hyperinsulinism [11].

Biological context of Persistent Hyperinsulinemia Hypoglycemia of Infancy

Mutations in the high-affinity sulfonylurea receptor (SUR)-1 cause one of the severe recessively inherited diffuse forms of congenital hyperinsulinism or, when associated with loss of heterozygosity, focal adenomatosis [12].
Recessive mutations of sulfonylurea receptor 1 (SUR1) and potassium inward rectifier 6.2 (Kir6.2), the two adjacent genes on chromosome 11p that comprise the beta-cell plasma membrane ATP-sensitive K(+) (K(ATP)) channels, are responsible for the most common form of congenital hyperinsulinism in children [13].

Anatomical context of Persistent Hyperinsulinemia Hypoglycemia of Infancy

AIMS/HYPOTHESIS: ATP-sensitive potassium (K(ATP)) channels are crucial for the regulation of insulin secretion from pancreatic beta cells and mutations in either the Kir6.2 or SUR1 subunit of this channel can cause congenital hyperinsulinism (CHI) [14].

Gene context of Persistent Hyperinsulinemia Hypoglycemia of Infancy

Unbalanced expression of 11p15 imprinted genes in focal forms of congenital hyperinsulinism: association with a reduction to homozygosity of a mutation in ABCC8 or KCNJ11 [15].
Molecular characterisation of glutamate dehydrogenase gene defects in Japanese patients with congenital hyperinsulinism/hyperammonaemia [16].
Congenital hyperinsulinism and hyperammonaemia (CHH) is caused by dysregulation of glutamate dehydrogenase (GDH) [16].
Reversible hypertrophic cardiomyopathy in congenital hyperinsulinism [17].

References

Serum glucagon counterregulatory hormonal response to hypoglycemia is blunted in congenital hyperinsulinism. Hussain, K., Bryan, J., Christesen, H.T., Brusgaard, K., Aguilar-Bryan, L. Diabetes (2005)
Disorders of glutamate metabolism. Kelly, A., Stanley, C.A. Mental retardation and developmental disabilities research reviews. (2001)
Cholelithiasis in a newborn following treatment with the somatostatin analogue octreotide. Radetti, G., Gentili, L., Paganini, C., Messner, H. Eur. J. Pediatr. (2000)
A new subtype of autosomal dominant diabetes attributable to a mutation in the gene for sulfonylurea receptor 1. Huopio, H., Otonkoski, T., Vauhkonen, I., Reimann, F., Ashcroft, F.M., Laakso, M. Lancet (2003)
A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels. Lin, Y.W., MacMullen, C., Ganguly, A., Stanley, C.A., Shyng, S.L. J. Biol. Chem. (2006)
Glutaminolysis and insulin secretion: from bedside to bench and back. Kelly, A., Li, C., Gao, Z., Stanley, C.A., Matschinsky, F.M. Diabetes (2002)
Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes. Henwood, M.J., Kelly, A., Macmullen, C., Bhatia, P., Ganguly, A., Thornton, P.S., Stanley, C.A. J. Clin. Endocrinol. Metab. (2005)
Severe congenital hyperinsulinism caused by a mutation in the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium channel impairing trafficking and function. Marthinet, E., Bloc, A., Oka, Y., Tanizawa, Y., Wehrle-Haller, B., Bancila, V., Dubuis, J.M., Philippe, J., Schwitzgebel, V.M. J. Clin. Endocrinol. Metab. (2005)
Acute insulin responses to calcium and tolbutamide do not differentiate focal from diffuse congenital hyperinsulinism. Giurgea, I., Laborde, K., Touati, G., Bellanné-Chantelot, C., Nassogne, M.C., Sempoux, C., Jaubert, F., Khoa, N., Chigot, V., Rahier, J., Brunelle, F., Nihoul-Fékété, C., Dunne, M.J., Stanley, C., Saudubray, J.M., Robert, J.J., de Lonlay, P. J. Clin. Endocrinol. Metab. (2004)
Short- and long-term use of octreotide in the treatment of congenital hyperinsulinism. Thornton, P.S., Alter, C.A., Katz, L.E., Baker, L., Stanley, C.A. J. Pediatr. (1993)
Octreotide in hyperinsulinism. Barrons, R.W. The Annals of pharmacotherapy. (1997)
Dysregulation of insulin secretion in children with congenital hyperinsulinism due to sulfonylurea receptor mutations. Grimberg, A., Ferry, R.J., Kelly, A., Koo-McCoy, S., Polonsky, K., Glaser, B., Permutt, M.A., Aguilar-Bryan, L., Stafford, D., Thornton, P.S., Baker, L., Stanley, C.A. Diabetes (2001)
Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor. Thornton, P.S., MacMullen, C., Ganguly, A., Ruchelli, E., Steinkrauss, L., Crane, A., Aguilar-Bryan, L., Stanley, C.A. Diabetes (2003)
Characterisation of new KATP-channel mutations associated with congenital hyperinsulinism in the Finnish population. Reimann, F., Huopio, H., Dabrowski, M., Proks, P., Gribble, F.M., Laakso, M., Otonkoski, T., Ashcroft, F.M. Diabetologia (2003)
Unbalanced expression of 11p15 imprinted genes in focal forms of congenital hyperinsulinism: association with a reduction to homozygosity of a mutation in ABCC8 or KCNJ11. Fournet, J.C., Mayaud, C., de Lonlay, P., Gross-Morand, M.S., Verkarre, V., Castanet, M., Devillers, M., Rahier, J., Brunelle, F., Robert, J.J., Nihoul-Fékété, C., Saudubray, J.M., Junien, C. Am. J. Pathol. (2001)
Molecular characterisation of glutamate dehydrogenase gene defects in Japanese patients with congenital hyperinsulinism/hyperammonaemia. Fujioka, H., Okano, Y., Inada, H., Asada, M., Kawamura, T., Hase, Y., Yamano, T. Eur. J. Hum. Genet. (2001)
Reversible hypertrophic cardiomyopathy in congenital hyperinsulinism. Massin, M.M., Van Elmbt, G., Soyeur, D. Acta cardiologica. (1999)