In:
Diabetes, American Diabetes Association, Vol. 55, No. 4 ( 2006-04-01), p. 1034-1042
Abstract:
Delayed-rectifier K+ currents (IDR) in pancreatic β-cells are thought to contribute to action potential repolarization and thereby modulate insulin secretion. The voltage-gated K+ channel, KV2.1, is expressed in β-cells, and the biophysical characteristics of heterologously expressed channels are similar to those of IDR in rodent β-cells. A novel peptidyl inhibitor of KV2.1/KV2.2 channels, guangxitoxin (GxTX)-1 (half-maximal concentration ∼1 nmol/l), has been purified, characterized, and used to probe the contribution of these channels to β-cell physiology. In mouse β-cells, GxTX-1 inhibits 90% of IDR and, as for KV2.1, shifts the voltage dependence of channel activation to more depolarized potentials, a characteristic of gating-modifier peptides. GxTX-1 broadens the β-cell action potential, enhances glucose-stimulated intracellular calcium oscillations, and enhances insulin secretion from mouse pancreatic islets in a glucose-dependent manner. These data point to a mechanism for specific enhancement of glucose-dependent insulin secretion by applying blockers of the β-cell IDR, which may provide advantages over currently used therapies for the treatment of type 2 diabetes.
Type of Medium:
Online Resource
ISSN:
0012-1797
,
1939-327X
DOI:
10.2337/diabetes.55.04.06.db05-0788
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2006
detail.hit.zdb_id:
1501252-9
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