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Glucose inhibits glucagon secretion by a direct effect on mouse pancreatic alpha cells

Vieira, E.; Salehi, S Albert LU and Gylfe, E. (2007) In Diabetologia 50(2). p.370-379
Abstract
Aims/hypothesis The mechanisms by which glucose regulates glucagon release are poorly understood. The present study aimed to clarify the direct effects of glucose on the glucagon-releasing alpha cells and those effects mediated by paracrine islet factors. Materials and methods Glucagon, insulin and somatostatin release were measured from incubated mouse pancreatic islets and the cytoplasmic Ca2+ concentration ([Ca2+](i)) recorded in isolated mouse alpha cells. Results Glucose inhibited glucagon release with maximal effect at 7 mmol/l. Since this concentration corresponded to threshold stimulation of insulin secretion, it is unlikely that inhibition of glucagon secretion is mediated by beta cell factors. Although somatostatin secretion data... (More)
Aims/hypothesis The mechanisms by which glucose regulates glucagon release are poorly understood. The present study aimed to clarify the direct effects of glucose on the glucagon-releasing alpha cells and those effects mediated by paracrine islet factors. Materials and methods Glucagon, insulin and somatostatin release were measured from incubated mouse pancreatic islets and the cytoplasmic Ca2+ concentration ([Ca2+](i)) recorded in isolated mouse alpha cells. Results Glucose inhibited glucagon release with maximal effect at 7 mmol/l. Since this concentration corresponded to threshold stimulation of insulin secretion, it is unlikely that inhibition of glucagon secretion is mediated by beta cell factors. Although somatostatin secretion data seemed consistent with a role of this hormone in glucose-inhibited glucagon release, a somatostatin receptor type 2 antagonist stimulated glucagon release without diminishing the inhibitory effect of glucose. In islets exposed to tolbutamide plus 8 mmol/l K+, glucose inhibited glucagon secretion without stimulating the release of insulin and somatostatin, indicating a direct inhibitory effect on the alpha cells that was independent of ATP-sensitive K+ channels. lucose lowered [Ca2+](i) of individual alpha cells independently of somatostatin and beta cell factors (insulin, Zn2+ and gamma-aminobutyric acid). Glucose suppression of glucagon release was prevented by inhibitors of the sarco(endo)plasmic reticulum Ca2+-ATPase, which abolished the [Ca2+](i)-lowering effect of glucose on isolated alpha cells. Conclusions/interpretation Beta cell factors or somatostatin do not seem to mediate glucose inhibition of glucagon secretion. We instead propose that glucose has a direct inhibitory effect on mouse alpha cells by suppressing a depolarising Ca2+ store-operated current. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
signal transduction, insulin secretion, calcium signalling, glucagon, somatostatin (SRIF)
in
Diabetologia
volume
50
issue
2
pages
370 - 379
publisher
Springer Verlag
external identifiers
  • wos:000243323200016
  • scopus:34047096301
ISSN
1432-0428
DOI
10.1007/s00125-006-0511-1
language
English
LU publication?
yes
id
240eec7a-2ab0-4c0f-a068-3e1d40d89159 (old id 679492)
date added to LUP
2007-12-20 14:09:41
date last changed
2017-10-22 03:35:30
@article{240eec7a-2ab0-4c0f-a068-3e1d40d89159,
  abstract     = {Aims/hypothesis The mechanisms by which glucose regulates glucagon release are poorly understood. The present study aimed to clarify the direct effects of glucose on the glucagon-releasing alpha cells and those effects mediated by paracrine islet factors. Materials and methods Glucagon, insulin and somatostatin release were measured from incubated mouse pancreatic islets and the cytoplasmic Ca2+ concentration ([Ca2+](i)) recorded in isolated mouse alpha cells. Results Glucose inhibited glucagon release with maximal effect at 7 mmol/l. Since this concentration corresponded to threshold stimulation of insulin secretion, it is unlikely that inhibition of glucagon secretion is mediated by beta cell factors. Although somatostatin secretion data seemed consistent with a role of this hormone in glucose-inhibited glucagon release, a somatostatin receptor type 2 antagonist stimulated glucagon release without diminishing the inhibitory effect of glucose. In islets exposed to tolbutamide plus 8 mmol/l K+, glucose inhibited glucagon secretion without stimulating the release of insulin and somatostatin, indicating a direct inhibitory effect on the alpha cells that was independent of ATP-sensitive K+ channels. lucose lowered [Ca2+](i) of individual alpha cells independently of somatostatin and beta cell factors (insulin, Zn2+ and gamma-aminobutyric acid). Glucose suppression of glucagon release was prevented by inhibitors of the sarco(endo)plasmic reticulum Ca2+-ATPase, which abolished the [Ca2+](i)-lowering effect of glucose on isolated alpha cells. Conclusions/interpretation Beta cell factors or somatostatin do not seem to mediate glucose inhibition of glucagon secretion. We instead propose that glucose has a direct inhibitory effect on mouse alpha cells by suppressing a depolarising Ca2+ store-operated current.},
  author       = {Vieira, E. and Salehi, S Albert and Gylfe, E.},
  issn         = {1432-0428},
  keyword      = {signal transduction,insulin secretion,calcium signalling,glucagon,somatostatin (SRIF)},
  language     = {eng},
  number       = {2},
  pages        = {370--379},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Glucose inhibits glucagon secretion by a direct effect on mouse pancreatic alpha cells},
  url          = {http://dx.doi.org/10.1007/s00125-006-0511-1},
  volume       = {50},
  year         = {2007},
}