Journal article

Publication year: 2004

Pages: 277-283

Journal: Diabetologia

Volume number: 47

Issue number: 2

ISSN: 0012-186X

Open access status: Bronze

DOI Link: https://doi.org/10.1007/s00125-003-1299-x

Publisher: Springer

Abstract: 

Aims/hypothesis. The ATP-regulated potassium (K-ATP) channel in the pancreatic beta cell couples the metabolic state to electrical activity. The primary regulator of the K-ATP channel is generally accepted to be changes in ATP/ADP ratio, where ATP inhibits and ADP activates channel activity. Recently, we showed that long-chain CoA (LC-CoA) esters form a new class of potent K-ATP channel activators in rodents, as studied in inside-out patches.

Methods. In this study we have investigated the effects of LC-CoA esters in human pancreatic beta cells using the inside-out and whole-cell configurations of the patch clamp technique.

Results. Human K-ATP channels were potently activated by acyl-CoA esters with a chain length exceeding 12 carbons. Activation by LC-CoA esters did not require the presence of Mg2+ or adenine nucleotides. A detailed characterization of the concentration-dependent relationship showed an EC50 of 0.7+/-0.1 mumol/l. Furthermore, in the presence of an ATP/ADP ratio of 10 (1.1 mmol/l total adenine nucleotides), whole-cell K-ATP channel currents increased approximately six-fold following addition of 1 mumol/l LC-CoA ester. The presence of 1 mumol/l LC-CoA in the recording pipette solution increased beta-cell input conductance, from 0.5+/-0.2 nS to 2.5+/-1.3 nS.

Conclusion/interpretation. Taken together, these results show that LC-CoA esters are potent activators of the K-ATP channel in human pancreatic beta cells. The fact that LC-CoA esters also stimulate K-ATP channel activity recorded in the whole-cell configuration, points to the ability of these compounds to have an important modulatory role of human beta-cell electrical activity under both physiological and pathophysiological conditions.

Harvard Citation style: Bränström, R., Aspinwall, C., Välimäki, S., Östensson, C., Tibell, A., Eckhard, M., et al. (2004) Long-chain CoA esters activate human pancreatic beta-cell K_ATP channels:: potential role in Type 2 diabetes, Diabetologia, 47(2), pp. 277-283. https://doi.org/10.1007/s00125-003-1299-x

APA Citation style: Bränström, R., Aspinwall, C., Välimäki, S., Östensson, C., Tibell, A., Eckhard, M., Brandhorst, H., Corkey, B., Berggren, P., & Larsson, O. (2004). Long-chain CoA esters activate human pancreatic beta-cell K_ATP channels:: potential role in Type 2 diabetes. Diabetologia. 47(2), 277-283. https://doi.org/10.1007/s00125-003-1299-x