Delayed rectifier K+ channel overexpression in transgenic islets and beta-cells associated with impaired glucose responsiveness

Glucose stimulation of pancreatic beta-cell insulin secretion is closely coupled to alterations in ion channel conductances and intracellular Ca2+ ([Ca2+]i). To further examine this relationship after augmentation of voltage-dependent K+ channel expression, transgenic mice were produced which specif...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 1994-11, Vol.269 (45), p.27787-27790
Main Authors: L H Philipson, M P Rosenberg, A Kuznetsov, M E Lancaster, J F Worley, 3rd, M W Roe, I D Dukes
Format: Article
Language:English
Subjects:
Animals
Blood Glucose - metabolism
Calcium - metabolism
Cells, Cultured
CHO Cells
Cricetinae
Glucose - pharmacology
Humans
In Vitro Techniques
Insulin - metabolism
Insulin Secretion
Insulinoma - metabolism
Islets of Langerhans - drug effects
Islets of Langerhans - metabolism
Islets of Langerhans - physiology
Membrane Potentials - drug effects
Mice
Mice, Transgenic
Pancreatic Neoplasms - metabolism
Potassium Channels - biosynthesis
Potassium Channels - isolation & purification
Potassium Channels - physiology
Rats
Tetraethylammonium
Tetraethylammonium Compounds - pharmacology
Transfection
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Glucose stimulation of pancreatic beta-cell insulin secretion is closely coupled to alterations in ion channel conductances and intracellular Ca2+ ([Ca2+]i). To further examine this relationship after augmentation of voltage-dependent K+ channel expression, transgenic mice were produced which specifically overexpress a human insulinoma-derived, tetraethylammonium (TEA)-insensitive delayed rectifier K+ channel in their pancreatic beta-cells as shown by immunoblot of isolated islets and immunohistochemical analysis of pancreas sections. Whole-cell current recordings confirmed the presence of high amplitude TEA-resistant K+ currents in transgenic islet cells, whose expression correlated with hyperglycemia and hypoinsulinemia. Stable overexpression of the channel in insulinoma cells attenuated glucose-activated increases in [Ca2+]i and prevented the induction of TEA-dependent [Ca2+]i oscillations. These results, employing the first ion channel transgenic mouse, demonstrate the importance of membrane potential regulation in excitation-secretion coupling in the pancreatic beta-cell.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)46851-2