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Carbon monoxide sti...
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Lundquist, IngmarLund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups
(author)
Carbon monoxide stimulates insulin release and propagates Ca2+ signals between pancreatic beta-cells
- Article/chapterEnglish2003
Publisher, publication year, extent ...
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American Physiological Society,2003
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LIBRIS-ID:oai:lup.lub.lu.se:e3bf891d-dc2e-420a-8203-bc00748a0341
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https://lup.lub.lu.se/record/299513URI
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https://doi.org/10.1152/ajpendo.00498.2002DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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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.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Alm, PerLund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)pat-pal
(author)
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Salehi, S AlbertLund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)farm-sal
(author)
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Henningsson, RagnarLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)farm-rhe
(author)
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Grapengiesser, E
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Hellman, B
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Islet cell physiologyForskargrupper vid Lunds universitet
(creator_code:org_t)
Related titles
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In:American Journal of Physiology: Endocrinology and Metabolism: American Physiological Society285:5, s. 1055-10631522-15550193-1849
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