K(ATP) channels and insulin secretion disorders.

@article{Huopio2002KATPCA,
  title={K(ATP) channels and insulin secretion disorders.},
  author={Hanna Huopio and Show-Ling Shyng and Timo Otonkoski and Colin G. Nichols},
  journal={American journal of physiology. Endocrinology and metabolism},
  year={2002},
  volume={283 2},
  pages={
          E207-16
        }
}
  • H. HuopioS. Shyng C. Nichols
  • Published 1 August 2002
  • Biology, Medicine
  • American journal of physiology. Endocrinology and metabolism
ATP-sensitive potassium (K(ATP)) channels are inhibited by intracellular ATP and activated by ADP. Nutrient oxidation in beta-cells leads to a rise in [ATP]-to-[ADP] ratios, which in turn leads to reduced K(ATP) channel activity, depolarization, voltage-dependent Ca(2+) channel activation, Ca(2+) entry, and exocytosis. Persistent hyperinsulinemic hypoglycemia of infancy (HI) is a genetic disorder characterized by dysregulated insulin secretion and, although rare, causes severe mental… 

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...

References

SHOWING 1-10 OF 85 REFERENCES

Diverse roles of K(ATP) channels learned from Kir6.2 genetically engineered mice.

Both the genetic defect in glucose-induced insulin secretion and the acquired insulin resistance due to environmental factors are necessary to develop diabetes in Kir6.2 knockout mice, which provide a model of type 2 diabetes and clarify the various roles of K(ATP) channels in endocrine pancreatic function.

Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes.

The data indicate that normal K(ATP) channel activity is critical for maintenance of euglycemia and that overactivity can cause diabetes by inhibiting insulin secretion.

Adenosine Diphosphate as an Intracellular Regulator of Insulin Secretion

By binding to SUR NBF2 and antagonizing ATP inhibition of KATP channels, intracellular MgADP may regulate insulin secretion.

Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice.

The data indicate that the KATP channel in pancreatic beta cells is a key regulator of both glucose- and sulfonylurea-induced insulin secretion and suggest also that the H2O channel in skeletal muscle might be involved in insulin action.

Familial hyperinsulinism and pancreatic beta-cell ATP-sensitive potassium channels.

Nearly 50 mutations, in both channel subunits, that abolish or alter the regulation of beta-cell KATP channels have been identified in patients with the recessive form of PHHI.

Activation and inhibition of K-ATP currents by guanine nucleotides is mediated by different channel subunits.

It is shown that mutation of the lysine residue in the Walker A motif of either the first (K719A) or second (K1384M) nucleotide-binding domain of SUR1 abolished both the potentiatory effects of GTP and GDP on K-ATP currents and their ability to support stimulation by diazoxide, arguing that the stimulatoryeffects of guanine nucleotides require the presence of both Walker A lysines.

ATP-sensitive potassium channels.

MgADP Antagonism to Mg2+-independent ATP Binding of the Sulfonylurea Receptor SUR1*

Results show that SUR1, unlike other ABC proteins, strongly binds ATP at NBF1 even in the absence of Mg2+ and that MgADP, through binding at N BF2, antagonizes the Mg 2+-independent high affinity ATP binding atNBF1.

Molecular determinants of KATP channel inhibition by ATP

It is found that Kir6.2 is highly selective for ATP, and that both the adenine moiety and the β‐phosphate contribute to specificity, and several mutations that significantly reduce ATP inhibition are identified.

A Nonsense Mutation in the Inward Rectifier Potassium Channel Gene, Kir6.2, Is Associated With Familial Hyperinsulinism

Data provide evidence that mutations in the Kir6.2 sub-unit of the islet β-cell KATP channel are associated with the HI phenotype and suggest that the majority of HI cases are not attributable to mutation in the coding region of the Kir 6.2 gene.
...