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Carbon monoxide stimulates insulin release and propagates Ca2+ signals between pancreatic beta-cells

Lundquist, Ingmar LU ; Alm, Per LU ; Salehi, S Albert LU ; Henningsson, Ragnar LU ; Grapengiesser, E and Hellman, B (2003) In American Journal of Physiology: Endocrinology and Metabolism 285(5). p.1055-1063
Abstract
A key question for understanding the mechanisms of pulsatile insulin release is how the underlying beta-cell oscillations of the cytoplasmic Ca2+ concentration ([Ca2+](i)) are synchronized within and among the islets in the pancreas. Nitric oxide has been proposed to coordinate the activity of the beta-cells by precipitating transients of [Ca2+](i). Comparing ob/ob mice and lean controls, we have now studied the action of carbon monoxide (CO), another neurotransmitter with stimulatory effects on cGMP production. A strong immunoreactivity for the CO-producing constitutive heme oxygenase (HO-2) was found in ganglionic cells located in the periphery of the islets and in almost all islet endocrine cells. Islets from ob/ob mice had sixfold... (More)
A key question for understanding the mechanisms of pulsatile insulin release is how the underlying beta-cell oscillations of the cytoplasmic Ca2+ concentration ([Ca2+](i)) are synchronized within and among the islets in the pancreas. Nitric oxide has been proposed to coordinate the activity of the beta-cells by precipitating transients of [Ca2+](i). Comparing ob/ob mice and lean controls, we have now studied the action of carbon monoxide (CO), another neurotransmitter with stimulatory effects on cGMP production. A strong immunoreactivity for the CO-producing constitutive heme oxygenase (HO-2) was found in ganglionic cells located in the periphery of the islets and in almost all islet endocrine cells. Islets from ob/ob mice had sixfold higher generation of CO ( 1 nmol.min(-1).mg protein(-1)) than the lean controls. This is 100-fold the rate for their constitutive production of NO. Moreover, islets from ob/ob mice showed a threefold increase in HO-2 expression and expressed inducible HO (HO-1). The presence of an excessive islet production of CO in the ob/ob mouse had its counterpart in a pronounced suppression of the glucose-stimulated insulin release from islets exposed to the HO inhibitor Zn-protoporhyrin (10 muM) and in a 16 times higher frequency of [Ca2+](i) transients in their beta-cells. Hemin (0.1 and 1.0 muM), the natural substrate for HO, promoted the appearance of [Ca2+](i) transients, and 10 muM of the HO inhibitors Zn-protoporphyrin and Cr-mesoporphyrin had a suppressive action both on the firing of transients and their synchronization. It is concluded that the increased islet production of CO contributes to the hyperinsulinemia in ob/ob mice. In addition to serving as a positive modulator of glucose-stimulated insulin release, CO acts as a messenger propagating Ca2+ signals with coordinating effects on the beta-cell rhythmicity. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
calcium ion, carbon monoxide
in
American Journal of Physiology: Endocrinology and Metabolism
volume
285
issue
5
pages
1055 - 1063
publisher
American Physiological Society
external identifiers
  • pmid:14534076
  • wos:000185822500015
ISSN
1522-1555
DOI
10.1152/ajpendo.00498.2002
language
English
LU publication?
yes
id
e3bf891d-dc2e-420a-8203-bc00748a0341 (old id 299513)
date added to LUP
2007-09-17 18:34:47
date last changed
2016-04-16 03:56:06
@article{e3bf891d-dc2e-420a-8203-bc00748a0341,
  abstract     = {A key question for understanding the mechanisms of pulsatile insulin release is how the underlying beta-cell oscillations of the cytoplasmic Ca2+ concentration ([Ca2+](i)) are synchronized within and among the islets in the pancreas. Nitric oxide has been proposed to coordinate the activity of the beta-cells by precipitating transients of [Ca2+](i). Comparing ob/ob mice and lean controls, we have now studied the action of carbon monoxide (CO), another neurotransmitter with stimulatory effects on cGMP production. A strong immunoreactivity for the CO-producing constitutive heme oxygenase (HO-2) was found in ganglionic cells located in the periphery of the islets and in almost all islet endocrine cells. Islets from ob/ob mice had sixfold higher generation of CO ( 1 nmol.min(-1).mg protein(-1)) than the lean controls. This is 100-fold the rate for their constitutive production of NO. Moreover, islets from ob/ob mice showed a threefold increase in HO-2 expression and expressed inducible HO (HO-1). The presence of an excessive islet production of CO in the ob/ob mouse had its counterpart in a pronounced suppression of the glucose-stimulated insulin release from islets exposed to the HO inhibitor Zn-protoporhyrin (10 muM) and in a 16 times higher frequency of [Ca2+](i) transients in their beta-cells. Hemin (0.1 and 1.0 muM), the natural substrate for HO, promoted the appearance of [Ca2+](i) transients, and 10 muM of the HO inhibitors Zn-protoporphyrin and Cr-mesoporphyrin had a suppressive action both on the firing of transients and their synchronization. It is concluded that the increased islet production of CO contributes to the hyperinsulinemia in ob/ob mice. In addition to serving as a positive modulator of glucose-stimulated insulin release, CO acts as a messenger propagating Ca2+ signals with coordinating effects on the beta-cell rhythmicity.},
  author       = {Lundquist, Ingmar and Alm, Per and Salehi, S Albert and Henningsson, Ragnar and Grapengiesser, E and Hellman, B},
  issn         = {1522-1555},
  keyword      = {calcium ion,carbon monoxide},
  language     = {eng},
  number       = {5},
  pages        = {1055--1063},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Endocrinology and Metabolism},
  title        = {Carbon monoxide stimulates insulin release and propagates Ca2+ signals between pancreatic beta-cells},
  url          = {http://dx.doi.org/10.1152/ajpendo.00498.2002},
  volume       = {285},
  year         = {2003},
}