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Expression levels of enzymes generating NO and CO in islets of murine and human diabetes

Artikel i vetenskaplig tidskrift
Författare I. Mohammed Al-Amily
I. Lundquist
Albert Salehi
Publicerad i Biochemical and Biophysical Research Communications
Volym 520
Nummer/häfte 2
Sidor 473-478
ISSN 0006-291X
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi
Sidor 473-478
Språk en
Länkar dx.doi.org/10.1016/j.bbrc.2019.10.0...
Ämnesord 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
Ämneskategorier Fysiologi, Cell- och molekylärbiologi

Sammanfattning

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.

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