WFRF:(Rorsman N. J. G.)
Sökning: WFRF:(Rorsman N. J. G.) > GLP-1 stimulates in...
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04894naa a2200673 4500 | |
| 001 | oai:gup.ub.gu.se/229691 | |
| 003 | SwePub | |
| 008 | 240528s2015 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://gup.ub.gu.se/publication/2296912 URI |
| 024 | 7 | a https://doi.org/10.1172/jci819752 DOI |
| 040 | a (SwePub)gu | |
| 041 | a eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Shigeto, Makotou Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology4 aut0 (Swepub:gu)xshigm |
| 245 | 1 0 | a GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation |
| 264 | 1 | b American Society for Clinical Investigation,c 2015 |
| 520 | a Strategies aimed at mimicking or enhancing the action of the incretin hormone glucagon-like peptide 1 (GLP-1) therapeutically improve glucose-stimulated insulin secretion (GSIS); however, it is not clear whether GLP-1 directly drives insulin secretion in pancreatic islets. Here, we examined the mechanisms by which GLP-1 stimulates insulin secretion in mouse and human islets. We found that GLP-1 enhances GSIS at a half-maximal effective concentration of 0.4 pM. Moreover, we determined that GLP-1 activates PLC, which increases submembrane diacylglycerol and thereby activates PKC, resulting in membrane depolarization and increased action potential firing and subsequent stimulation of insulin secretion. The depolarizing effect of GLP-1 on electrical activity was mimicked by the PKC activator PMA, occurred without activation of PKA, and persisted in the presence of PKA inhibitors, the K-ATP channel blacker tolbutamide, and the L-type Ca2+ channel blacker isradipine; however, depolarization was abolished by lowering extracellular Na+. The PKC-dependent effect of GLP-1 on membrane potential and electrical activity was mediated by activation of NW-permeable TRPM4 and TRPM5 channels by mobilization of intracellular Ca2+ from thapsigargin-sensitive Ca2+ stores. Concordantly, GLP-1 effects were negligible in Trpm4 or Trpm5 KO islets. These data provide important insight into the therapeutic action of GLP-1 and suggest that circulating levels of this hormone directly stimulate insulin secretion by beta cells. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Fysiologi0 (SwePub)301062 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Physiology0 (SwePub)301062 hsv//eng |
| 653 | a GLUCAGON-LIKE PEPTIDE-1 | |
| 653 | a PANCREATIC BETA-CELLS | |
| 653 | a TYPE-2 | |
| 653 | a DIABETIC-PATIENTS | |
| 653 | a CATION CHANNEL TRPM4 | |
| 653 | a PROTEIN-KINASE-C | |
| 653 | a ACTION-POTENTIALS | |
| 653 | a MOUSE ISLETS | |
| 653 | a RAT ISLETS | |
| 653 | a B-CELLS | |
| 653 | a GLUCOSE | |
| 700 | 1 | a Ramracheya, R.4 aut |
| 700 | 1 | a Tarasov, A. I.4 aut |
| 700 | 1 | a Cha, Chae Youngu Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology4 aut |
| 700 | 1 | a Chibalina, M. V.4 aut |
| 700 | 1 | a Hastoy, B.4 aut |
| 700 | 1 | a Philippaert, K.4 aut |
| 700 | 1 | a Reinbothe, Thomas,d 1981u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology4 aut0 (Swepub:gu)xreith |
| 700 | 1 | a Rorsman, N.4 aut |
| 700 | 1 | a Salehi, Albertu Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology4 aut0 (Swepub:gu)xsalea |
| 700 | 1 | a Sones, W. R.4 aut |
| 700 | 1 | a Vergari, E.4 aut |
| 700 | 1 | a Weston, C.4 aut |
| 700 | 1 | a Gorelik, J.4 aut |
| 700 | 1 | a Katsura, M.4 aut |
| 700 | 1 | a Nikolaev, V. O.4 aut |
| 700 | 1 | a Vennekens, R.4 aut |
| 700 | 1 | a Zaccolo, M.4 aut |
| 700 | 1 | a Galione, A.4 aut |
| 700 | 1 | a Johnson, P. R. V.4 aut |
| 700 | 1 | a Kaku, K.4 aut |
| 700 | 1 | a Ladds, G.4 aut |
| 700 | 1 | a Rorsman, Patrik,d 1959u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xrorpa |
| 710 | 2 | a Göteborgs universitetb Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi4 org |
| 773 | 0 | t Journal of Clinical Investigationd : American Society for Clinical Investigationg 125:12, s. 4714-4728q 125:12<4714-4728x 0021-9738x 1558-8238 |
| 856 | 4 | u http://www.jci.org/articles/view/81975/files/pdf |
| 856 | 4 8 | u https://gup.ub.gu.se/publication/229691 |
| 856 | 4 8 | u https://doi.org/10.1172/jci81975 |
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