PMID- 11099479
OWN - NLM
STAT- MEDLINE
DCOM- 20010208
LR  - 20220129
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 14
IP  - 15
DP  - 2000 Dec
TI  - Glucose- and arginine-induced insulin secretion by human pancreatic beta-cells: 
      the role of HERG K(+) channels in firing and release.
PG  - 2601-10
AB  - The human ether-a-go-go-related genes (herg) are expressed in tissues other than 
      heart and brain where the HERG K(+) channels are known to regulate the 
      repolarization of the heart action potential and the neuronal spike-frequency 
      accommodation. We provide evidence that herg1 transcripts are present in human 
      pancreatic islets that were used to study both insulin secretion and electrical 
      activity with radioimmunoassay and single cell perforated patch-clamp techniques, 
      respectively. Glucose- and arginine-induced islets insulin secretion data 
      suggested a net increase of release under perfusion with antiarrhythmic drugs 
      known to selectively block HERG channels. Indeed we could routinely isolate a 
      K(+) current that was recognized as biophysically and pharmacologically similar 
      to the HERG current. An analysis of the glucose- and arginine-induced electrical 
      activity (several applications during 30 min) in terms of firing frequency and 
      putative insulin release was done in control and in the presence of selective 
      blockers of HERG channels: the firing frequency and the release increased by 32% 
      and 77%, respectively. It is concluded that HERG channels have a crucial role in 
      regulating insulin secretion and firing of human beta-cells. This raises the 
      possibility that some genetically characterized hyperinsulinemic diseases of 
      unknown origin might involve mutations in the HERG channels.
FAU - Rosati, B
AU  - Rosati B
AD  - Department of Biotechnology and Biosciences, University of Milano-Bicocca, 
      I-20126 Milano, Italy.
FAU - Marchetti, P
AU  - Marchetti P
FAU - Crociani, O
AU  - Crociani O
FAU - Lecchi, M
AU  - Lecchi M
FAU - Lupi, R
AU  - Lupi R
FAU - Arcangeli, A
AU  - Arcangeli A
FAU - Olivotto, M
AU  - Olivotto M
FAU - Wanke, E
AU  - Wanke E
LA  - eng
GR  - 1046/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Benzimidazoles)
RN  - 0 (Cation Transport Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ERG protein, human)
RN  - 0 (ERG1 Potassium Channel)
RN  - 0 (Ether-A-Go-Go Potassium Channels)
RN  - 0 (Insulin)
RN  - 0 (KATP Channels)
RN  - 0 (KCNH2 protein, human)
RN  - 0 (KCNH6 protein, human)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Inwardly Rectifying)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 0 (Sulfanilamides)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcriptional Regulator ERG)
RN  - 0 (uK-ATP-1 potassium channel)
RN  - 138490-53-6 (WAY 123398)
RN  - 94ZLA3W45F (Arginine)
RN  - 982XCM1FOI (Tolbutamide)
RN  - IY9XDZ35W2 (Glucose)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - ATP-Binding Cassette Transporters
MH  - Arginine/*pharmacology
MH  - Benzimidazoles/pharmacology
MH  - *Cation Transport Proteins
MH  - *DNA-Binding Proteins
MH  - ERG1 Potassium Channel
MH  - Electric Conductivity
MH  - Ether-A-Go-Go Potassium Channels
MH  - Glucose/*pharmacology
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin Secretion
MH  - Islets of Langerhans/drug effects/*metabolism
MH  - KATP Channels
MH  - Patch-Clamp Techniques
MH  - Potassium/metabolism
MH  - Potassium Channel Blockers
MH  - Potassium Channels/*metabolism
MH  - Potassium Channels, Inwardly Rectifying
MH  - *Potassium Channels, Voltage-Gated
MH  - Radioimmunoassay
MH  - Reproducibility of Results
MH  - Sulfanilamides/pharmacology
MH  - Tolbutamide/pharmacology
MH  - *Trans-Activators
MH  - Transcriptional Regulator ERG
EDAT- 2000/12/02 11:00
MHDA- 2001/03/03 10:01
CRDT- 2000/12/02 11:00
PHST- 2000/12/02 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/12/02 11:00 [entrez]
AID - 14/15/2601 [pii]
AID - 10.1096/fj.00-0077com [doi]
PST - ppublish
SO  - FASEB J. 2000 Dec;14(15):2601-10. doi: 10.1096/fj.00-0077com.