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GLP-1 suppresses gl...
GLP-1 suppresses glucagon secretion in human pancreatic alpha-cells by inhibition of P/Q-type Ca2+ channels
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Ramracheya, R. (författare)
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Chapman, C. (författare)
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Chibalina, M. (författare)
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- Dou, Haiqiang, 1984 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Miranda, Caroline (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Gonzalez, A. (författare)
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Moritoh, Y. (författare)
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Shigeto, M. (författare)
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Zhang, Q. (författare)
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Braun, M. (författare)
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Clark, A. (författare)
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Johnson, P. R. (författare)
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- Rorsman, Patrik, 1959 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Briant, L. J. B. (författare)
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(creator_code:org_t)
- 2018-09-05
- 2018
- Engelska.
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 6:17
- Relaterad länk:
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https://physoc.onlin...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Glucagon is the body's main hyperglycemic hormone, and its secretion is dysregulated in type 2 diabetes mellitus (T2DM). The incretin hormone glucagon-like peptide-1 (GLP-1) is released from the gut and is used in T2DM therapy. Uniquely, it both stimulates insulin and inhibits glucagon secretion and thereby lowers plasma glucose levels. In this study, we have investigated the action of GLP-1 on glucagon release from human pancreatic islets. Immunocytochemistry revealed that only <0.5% of the alpha-cells possess detectable GLP-1R immunoreactivity. Despite this, GLP-1 inhibited glucagon secretion by 50-70%. This was due to a direct effect on alpha-cells, rather than paracrine signaling, because the inhibition was not reversed by the insulin receptor antagonist S961 or the somatostatin receptor-2 antagonist CYN154806. The inhibitory effect of GLP-1 on glucagon secretion was prevented by the PKA-inhibitor Rp-cAMPS and mimicked by the adenylate cyclase activator forskolin. Electrophysiological measurements revealed that GLP-1 decreased action potential height and depolarized interspike membrane potential. Mathematical modeling suggests both effects could result from inhibition of P/Q-type Ca2+ channels. In agreement with this, GLP-1 and omega-aga-toxin (a blocker of P/Q-type channels) inhibited glucagon secretion in islets depolarized by 70 mmol/L [K+](o), and these effects were not additive. Intracellular application of cAMP inhibited depolarization-evoked exocytosis in individual alpha-cells by a PKA-dependent (Rp-cAMPS-sensitive) mechanism. We propose that inhibition of glucagon secretion by GLP-1 involves activation of the few GLP-1 receptors present in the alpha-cell membrane. The resulting small elevation of cAMP leads to PKA-dependent inhibition of P/Q-type Ca2+ channels and suppression of glucagon exocytosis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- cAMP
- cyclic adenosine monophosphate
- GLP-1
- glucagon-like peptide 1
- K-ATP
- potassium ATP
- protein-kinase-a
- k-atp channels
- beta-cells
- delta-cells
- human islets
- fasting hyperglycemia
- electrical-activity
- potassium channels
- glucose
- regulation
- insulin-secretion
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Ramracheya, R.
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Chapman, C.
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Chibalina, M.
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Dou, Haiqiang, 1 ...
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Miranda, Carolin ...
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Gonzalez, A.
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visa fler...
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Moritoh, Y.
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Shigeto, M.
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Zhang, Q.
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Braun, M.
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Clark, A.
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Johnson, P. R.
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Rorsman, Patrik, ...
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Briant, L. J. B.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Physiological Re ...
- Av lärosätet
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Göteborgs universitet