The Walter B. Cannon Physiology in Perspective Lecture, 2007. ATP-sensitive K+ channels and disease: from molecule to malady.

@article{Ashcroft2007TheWB,
  title={The Walter B. Cannon Physiology in Perspective Lecture, 2007. ATP-sensitive K+ channels and disease: from molecule to malady.},
  author={Frances M. Ashcroft},
  journal={American journal of physiology. Endocrinology and metabolism},
  year={2007},
  volume={293 4},
  pages={
          E880-9
        }
}
  • F. Ashcroft
  • Published 24 July 2007
  • Biology
  • American journal of physiology. Endocrinology and metabolism
This essay is based on a lecture given to the American Physiological Society in honor of Walter B. Cannon, an advocate of homeostasis. It focuses on the role of the ATP-sensitive potassium K(+) (K(ATP)) channel in glucose homeostasis and, in particular, on its role in insulin secretion from pancreatic beta-cells. The beta-cell K(ATP) channel comprises pore-forming Kir6.2 and regulatory SUR1 subunits, and mutations in either type of subunit can result in too little or too much insulin release… 

Figures from this paper

Modeling K(ATP) channel gating and its regulation.

The K(ATP) channel and neonatal diabetes.

TLDR
This review focuses on mutations in the pore-forming K(ATP) channel subunit (Kir6.2) that cause Neonatal diabetes and discusses recent advances in the understanding of clinical features of neonatal diabetes, its underlying molecular mechanisms and their impact on treatment.

K Channel Mutations and Neonatal Diabetes

TLDR
This review focuses on mutations of Kir6.2, the pore-forming subunit and sulfonylurea receptor (SUR) 1, the regulatory subunit of the K ATP channel, which cause neonatal diabetes/DEND syndrome and also discusses the findings of the pathological mechanisms that are associated with Neonatal diabetes, and its neurological features.

ATP-sensitive potassium channels in health and disease.

  • R. ClarkP. Proks
  • Biology, Medicine
    Advances in experimental medicine and biology
  • 2010
TLDR
This chapter reviews the current understanding of the pancreatic beta-cell K(ATP) channel and highlights recent structural, functional and clinical advances.

Human KATP channelopathies: diseases of metabolic homeostasis

  • T. OlsonA. Terzic
  • Biology, Medicine
    Pflügers Archiv - European Journal of Physiology
  • 2009
TLDR
Advances in molecular medicine in the emerging field of human KATP channelopathies offer new opportunities for targeted individualized screening, early diagnosis, and tailored therapy.

KATP Channel Mutations and Neonatal Diabetes

TLDR
This review focuses on mutations of Kir6.2, the pore-forming subunit and sulfonylurea receptor (SUR) 1, the regulatory subunit of the KATP channel, which cause neonatal diabetes/DEND syndrome and also discusses the findings of the pathological mechanisms that are associated with Neonatal diabetes, and its neurological features.

SYMPOSIUM REVIEW: The role of the KATP channel in glucose homeostasis in health and disease: more than meets the islet

TLDR
This symposium review focuses on the current understanding of the role of the KATP channel in glucose homeostasis in health and disease.

Interaction between mutations in the slide helix of Kir6.2 associated with neonatal diabetes and neurological symptoms.

TLDR
Functional analysis revealed the F60Y mutation increases the intrinsic channel open probability (Po(0), thereby indirectly producing a marked decrease in channel inhibition by ATP and an increase in whole-cell K(ATP) currents, and interactions between slide helix residues can influence K( ATP) channel gating.

New insights into KATP channel gene mutations and neonatal diabetes mellitus

TLDR
The mechanism of action of mutations that lead to neonatal diabetes mellitus is discussed, work on the management of this disease is reviewed and atomic-resolution structures of the KATP channel complex have identified the binding sites for nucleotides and sulfonylurea drugs and shed light on how disease-causing mutations produce their functional effects.
...

References

SHOWING 1-10 OF 130 REFERENCES

Focus on Kir6.2: a key component of the ATP-sensitive potassium channel.

ATP-sensitive potassium channelopathies: focus on insulin secretion.

  • F. Ashcroft
  • Medicine, Biology
    The Journal of clinical investigation
  • 2005
TLDR
This review focuses on insulin secretory disorders, such as congenital hyperinsulinemia and neonatal diabetes, that result from mutations in K(ATP) channel genes, and considers the extent to which defective regulation of K( Atp) channel activity contributes to the etiology of type 2 diabetes.

Metabolic regulation of the pancreatic beta-cell ATP-sensitive K+ channel: a pas de deux.

TLDR
Evidence is provided that MgADP (or MgATP hydrolysis), acting at the regulatory subunit of the channel, shifts the ATP concentration-response curve into a range in which the channel pore can respond to dynamic changes in cytosolic ATP, orchestrating the pivotal role of ATP in metabolic regulation of the KATP channel.

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.

Differential nucleotide regulation of KATP channels by SUR1 and SUR2A.

Cardiac KATP channels in health and disease.

Roles of KATP channels as metabolic sensors in acute metabolic changes.

  • T. MikiS. Seino
  • Biology, Medicine
    Journal of molecular and cellular cardiology
  • 2005

Reconstitution of IKATP: An Inward Rectifier Subunit Plus the Sulfonylurea Receptor

TLDR
Gene mapping data indicate that these pancreatic β cell potassium channels are a complex composed of at least two subunits-BIR, a member of the inward rectifier potassium channel family, and SUR, a members of the ATP-binding cassette superfamily.

The essential role of the Walker A motifs of SUR 1 in K-ATP channel activation by Mg-ADP and diazoxide result in the closure of K-ATP channels in the β-cell plasma

TLDR
Results recorded in the control solution prior to application of the indicate that the WA lysine of NBD1 (but not NBD2) is nucleotide (Ohno-Shosaku et al., 1987).

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

TLDR
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.
...