Molecular Defects of ATP-Sensitive Potassium Channels in Congenital Hyperinsulinism

2012 ◽  
pp. 30-42 ◽  
Author(s):  
Show-Ling Shyng ◽  
Jeremy·D. Bushman ◽  
Emily B. Pratt ◽  
Qing Zhou
Keyword(s):  
Potassium Channels ◽  
Congenital Hyperinsulinism ◽  
Molecular Defects

scholarly journals In Vitro Recovery of ATP-Sensitive Potassium Channels in  -Cells From Patients With Congenital Hyperinsulinism of Infancy

Diabetes ◽  
2011 ◽  
Vol 60 (4) ◽  
pp. 1223-1228 ◽  
Author(s):  
P. D. Powell ◽  
C. Bellanne-Chantelot ◽  
S. E. Flanagan ◽  
S. Ellard ◽  
R. Rooman ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Congenital Hyperinsulinism ◽  
In Cells

scholarly journals Diagnosis of congenital Hyperinsulinism can occur not only in infancy but also in later age: a new flow chart from a single center experience

2020 ◽  
Vol 46 (1) ◽  
Author(s):  
Alberto Casertano ◽  
Arianna De Matteis ◽  
Enza Mozzillo ◽  
Francesco Maria Rosanio ◽  
Pietro Buono ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Laboratory Data ◽  
Late Presentation ◽  
Flow Chart ◽  
Molecular Defect ◽  
Congenital Hyperinsulinism ◽  
Molecular Defects ◽  
Diagnostic Algorithms ◽  
Metabolic Defects ◽  
Single Center Experience

Abstract Background Congenital Hyperinsulinism typically occurs with a neonatal hypoglycemia but can appear even in childhood or in adolescence with different types of glucose metabolism derangements. Current diagnostic algorithms don’t take into account cases with a late presentation. Patients and methods Clinical and laboratory data of twenty-two subjects diagnosed at Federico II University of Naples have been described: patients have been divided according to the molecular defect into channel defects, metabolic defects and unidentified molecular defects. A particular focus has been made on three cases with a late presentation. Results and conclusions Late presentation cases may not be identified by previous diagnostic algorithms. Consequently, it seems appropriate to design a new flow-chart starting from the age of presentation, also considering that late presentation cases can show glucose metabolism derangements other than hypoglycaemic crises such as diabetes, glucose intolerance, postprandial hypoglycaemia and gestational diabetes.

scholarly journals Molecular characterization of eag: a gene affecting potassium channels in Drosophila melanogaster.

Genetics ◽  
1991 ◽  
Vol 127 (3) ◽  
pp. 497-505 ◽  
Author(s):  
R Drysdale ◽  
J Warmke ◽  
R Kreber ◽  
B Ganetzky
Keyword(s):  
Drosophila Melanogaster ◽  
Potassium Channels ◽  
Gamma Ray ◽  
Genomic Library ◽  
Molecular Defects ◽  
Behavioral Abnormalities ◽  
Starting Point ◽  
Genes Encoding ◽  
Dna Fragment

Abstract Genes encoding proteins involved in the function of the nervous system can be identified via mutations causing behavioral abnormalities. An example is ether à go-go (eag) in Drosophila melanogaster, which was identified originally as an X-linked mutation that displayed ether-induced leg-shaking behavior. Electrophysiological and genetic evidence suggests that the product of the eag locus is intimately involved in the normal functioning of one or more types of voltage-gated potassium channels. To initiate a molecular analysis of eag we first generated a collection of deletions to pinpoint its cytological location. On the basis of this location, we identified an existing inversion, In(1)sc29, with one breakpoint at the eag locus and the other in the scute (sc) complex. A genomic library was prepared from In(1)sc29 and screened with a genomic DNA fragment that spanned the sc breakpoint to isolate DNA from the eag region. Beginning from this starting point over 85 kb of DNA were isolated by chromosome walking. Three additional eag alleles, including two dysgenesis-induced insertion mutations and a gamma-ray-induced insertional translocation, were located on the molecular map of the eag locus by Southern blot analysis. The molecular defects associated with these alleles encompass a total of 27 kb within the chromosome walk. A 10-kb transcript derived from this region, which is expressed most abundantly in heads, was identified on Northern blots. Two different eag mutations separated by over 20 kb interrupt the same transcript identifying it as the likely eag message. cDNAs representing a portion of this transcript have been isolated.(ABSTRACT TRUNCATED AT 250 WORDS)

Trafficking of ATP-sensitive potassium channels in health and disease

2007 ◽  
Vol 35 (5) ◽  
pp. 1055-1059 ◽  
Author(s):  
A. Sivaprasadarao ◽  
T.K. Taneja ◽  
J. Mankouri ◽  
A.J. Smith
Keyword(s):  
Insulin Secretion ◽  
Potassium Channels ◽  
Cell Surface ◽  
Genetic Diseases ◽  
Neonatal Diabetes ◽  
Katp Channels ◽  
Severe Form ◽  
Coated Vesicle ◽  
Congenital Hyperinsulinism ◽  
Sulfonylurea Receptor

KATP channels (ATP-sensitive potassium channels), comprising four subunits each of Kir6.2 (inwardly rectifying potassium channel 6.2) and the SUR1 (sulfonylurea receptor 1), play a central role in glucose-stimulated insulin secretion by the pancreatic β-cell. Changes in the number of channels at the cell surface are associated with genetic diseases of aberrant insulin secretion, including CHI (congenital hyperinsulinism) and NDM (neonatal diabetes mellitus). The present review summarizes advances in our understanding of the vesicular trafficking of normal KATP channels and how genetic mutations in Kir6.2 interfere with such trafficking. A mutation, E282K, causing CHI, was found to disrupt a DXE [di-acidic ER (endoplasmic reticulum)-exit signal], thereby preventing its assembly into COPII (coatamer protein II)-coated vesicles and subsequent ER exit. The resultant decrease in the cell-surface density of the channel could explain the disease phenotype. Two mutations, Y330C and F333I, reported in patients with NDM, disrupted an endocytic traffic signal, thereby impairing CCV (clathrin-coated vesicle) formation and endocytosis. The consequent increase in the density of KATP channels, together with an attenuated sensitivity to ATP reported previously, may account for the severe form of NDM.

scholarly journals A NovelKCNJ11Mutation Associated with Congenital Hyperinsulinism Reduces the Intrinsic Open Probability of β-Cell ATP-sensitive Potassium Channels

2005 ◽  
Vol 281 (5) ◽  
pp. 3006-3012 ◽  
Author(s):  
Yu-Wen Lin ◽  
Courtney MacMullen ◽  
Arupa Ganguly ◽  
Charles A. Stanley ◽  
Show-Ling Shyng
Keyword(s):  
Potassium Channels ◽  
Congenital Hyperinsulinism ◽  
Β Cell ◽  
Open Probability
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