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Expression levels o...
Expression levels of enzymes generating NO and CO in islets of murine and human diabetes
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- Mohammed Al-Amily, Israa (författare)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Lundquist, Ingmar (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Salehi, Albert (författare)
- University of Gothenburg,Lund University,Lunds universitet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- Engelska.
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; 520:2, s. 473-478
- Relaterad länk:
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http://dx.doi.org/10...
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Abstract
Ämnesord
Stäng
- The possible implication of the gasotransmitters NO and CO for the development of diabetes remains unresolved. Our previous investigations in rodents suggested NO being inhibitory, and CO stimulatory, to glucose-stimulated insulin secretion (GSIS). Here we studied the possible role of these gasotransmitters in both murine and human type 2 diabetes (T2D) by mapping the expression pattern of neural nitric oxide synthase (nNOS), inducible NOS (iNOS), constitutive heme oxygenase (HO-2), and inducible HO (HO-1) in isolated pancreatic islets. Two variants of obese murine diabetes with distinct phenotype, the db/db and the ob/ob mouse, were studied at the initiation of the diabetic condition. Plasma glucose and plasma insulin were recorded and β-cell expression levels of the different enzymes were measured with confocal microscopy and fluorescence intensity recordings. In human islets taken from nondiabetic controls (ND) and type 2 diabetes (T2D) the expression of the enzymes was analyzed by RNA-sequencing and qPCR. At the initiation of murine diabetes plasma glucose was slightly increased, whereas plasma insulin was extremely enhanced in both db/db and ob/ob mice. The β-cell expression of nNOS and iNOS was markedly increased over controls in db/db mice, known to develop severe diabetes, while it was very low in ob/ob mice, known to develop mild diabetes. HO-2 expression was unaffected in db/db and modestly decreased in ob/ob mice. HO-1 expression was slightly enhanced in ob/ob, but, in contrast, extremely enhanced in db/db mice, suggesting a counteracting, antidiabetic action by CO. Moreover, the diabetic pattern of highly increased nNOS, iNOS and HO-1 expression seen in db/db mice was also fully recognized in human T2D islets. These results suggest that increased expression of the NOS-enzymes, especially an early upregulation of nNOS, could be involved in the initial development of the severe diabetes of db/db mice as well as in human T2D. Hence, nNOS, iNOS and HO-1 might be regarded as interesting targets to take into consideration in the early treatment of a diabetic condition in different variants of T2D. © 2019 Elsevier Inc.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Enzymes
- Heme oxygenase 1 (HO-1)and HO-2
- Hormone secretion
- Nitric oxide synthase 1 (NOS1)and NOS2
- carbon monoxide
- gasotransmitter
- glucose
- heme oxygenase 1
- heme oxygenase 2
- inducible nitric oxide synthase
- insulin
- neuronal nitric oxide synthase
- nitric oxide
- animal tissue
- Article
- B lymphocyte
- confocal microscopy
- controlled study
- db/db mouse
- disease severity
- early intervention
- female
- fluorescence analysis
- glucose blood level
- human
- human tissue
- insulin blood level
- mouse
- non insulin dependent diabetes mellitus
- nonhuman
- ob/ob mouse
- pancreas islet
- priority journal
- protein expression
- real time polymerase chain reaction
- RNA sequence
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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