Targeted Overactivity of β Cell KATP Channels Induces Profound Neonatal Diabetes

@article{Koster2000TargetedOO,
  title={Targeted Overactivity of $\beta$ Cell KATP Channels Induces Profound Neonatal Diabetes},
  author={Jc. Koster and Barbara Marshall and Nancy J. Ensor and John A. Corbett and Cg. Nichols},
  journal={Cell},
  year={2000},
  volume={100},
  pages={645-654}
}
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TLDR
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ATP-sensitive K+ channel signaling in glucokinase-deficient diabetes.
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References

SHOWING 1-10 OF 138 REFERENCES
Abnormalities of pancreatic islets by targeted expression of a dominant-negative KATP channel.
  • T. Miki, F. Tashiro, S. Seino
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1997
TLDR
A high frequency of apoptotic beta cells before the appearance of hyperglycemia in the transgenic mice is found, suggesting that the KATP channel might play a significant role in beta cell survival in addition to its role in the regulation of insulin secretion.
Defective Pancreatic β-Cell Glycolytic Signaling in Hepatocyte Nuclear Factor-1α-deficient Mice*
TLDR
It is concluded that hepatocyte nuclear factor-1α diabetes results from defective β-cell glycolytic signaling, which is potentially correctable using substrates that bypass the defect.
Electrophysiology of Stimulus-Secretion Coupling in Human β-Cells
TLDR
It is suggested that combinations of Cm measurements and electrical activity/membrane current measurements may help define the roles of diverse electrical activity patterns, displayed by human β-cells, in stimulus-induced insulin secretion.
Adenosine Diphosphate as an Intracellular Regulator of Insulin Secretion
TLDR
By binding to SUR NBF2 and antagonizing ATP inhibition of KATP channels, intracellular MgADP may regulate insulin secretion.
Glucose action `beyond ionic events' in the pancreatic β cell
ATP-Sensitive K+ Channels in Pancreatic β-Cells: Spare-Channel Hypothesis
TLDR
A simple mathematical model is used to demonstrate that there is no major discrepancy and that, in fact, given the electrophysiological mechanisms existing in the β-cell, the extreme sensitivity of the channels to ATP is appropriate and even mandatory for their physiological function.
Delayed rectifier K+ channel overexpression in transgenic islets and beta-cells associated with impaired glucose responsiveness.
Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor
TLDR
It is shown that the primary site at which ATP acts to mediate K-ATP channel inhibition is located on Kir6.2, and that SUR1 is required for sensitivity to sulphonylureas and diazoxide and for activation by Mg-ADP.
Glucose modulation of ATP-sensitive K-currents in wild-type, homozygous and heterozygous glucokinase knock-out mice
TLDR
The idea that defective glycolytic metabolism, produced by a loss (-/- mice) or reduction ( + /- mice) of glucokinase activity, leads to defective KATP channel regulation and thereby to the selective loss, or reduction, of glucose-induced insulin secretion is supported.
Leptin Suppression of Insulin Secretion by the Activation of ATP-Sensitive K+ Channels in Pancreatic β-Cells
TLDR
An important physiological role for leptin as an inhibitor of insulin secretion is indicated and the failure of leptin to inhibit insulin secretion from the β-Cells of ob/ob and db/db mice may explain, in part, the development of hyperinsulinemia, insulin resistance, and the progression to NIDDM.
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