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Carlsson, Per-Ola
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Publications (10 of 179) Show all publications
Singh, K., Martinell, M., Luo, Z., Espes, D., Stålhammar, J., Sandler, S. & Carlsson, P.-O. (2019). Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes. Clinical and Experimental Immunology, 197(1), 64-73
Open this publication in new window or tab >>Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes
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2019 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 197, no 1, p. 64-73Article in journal (Refereed) Published
Abstract [en]

There is currently scarce knowledge of the immunological profile of patients with latent autoimmune diabetes mellitus in the adult (LADA) when compared with healthy controls (HC) and patients with classical type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective of this study was to investigate the cellular immunological profile of LADA patients and compare to HC and patients with T1D and T2D. All patients and age-matched HC were recruited from Uppsala County. Peripheral blood mononuclear cells were isolated from freshly collected blood to determine the proportions of immune cells by flow cytometry. Plasma concentrations of the cytokine interleukin (IL)-35 were measured by enzyme-linked immunosorbent assay (ELISA). The proportion of CD11c(+)CD123(-) antigen-presenting cells (APCs) was lower, while the proportions of CD11c(+)CD123(+) APCs and IL-35(+) tolerogenic APCs were higher in LADA patients than in T1D patients. The proportion of CD3(-)CD56(high)CD16(+) natural killer (NK) cells was higher in LADA patients than in both HC and T2D patients. The frequency of IL-35(+) regulatory T cells and plasma IL-35 concentrations in LADA patients were similar to those in T1D and T2D patients, but lower than in HC. The proportion of regulatory B cells in LADA patients was higher than in healthy controls, T1D and T2D patients, and the frequency of IL-35(+) regulatory B cells was higher than in T1D patients. LADA presents a mixed cellular immunological pattern with features overlapping with both T1D and T2D.

Keywords
Cellular immunology, IL-35, LADA, type 1 diabetes, type 2 diabetes
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-393134 (URN)10.1111/cei.13289 (DOI)000480400100004 ()30843600 (PubMedID)
Funder
Swedish Research Council, 2017-01343Swedish Research Council, 921-2014-7054Swedish Diabetes AssociationSwedish Child Diabetes FoundationEXODIAB - Excellence of Diabetes Research in SwedenNovo Nordisk
Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2019-09-24Bibliographically approved
Ullsten, S., Lau, J. & Carlsson, P.-O. (2019). Decreased beta-Cell Proliferation and Vascular Density in a Subpopulation of Low-Oxygenated Male Rat Islets. Journal of the Endocrine Society, 3(8), 1608-1616
Open this publication in new window or tab >>Decreased beta-Cell Proliferation and Vascular Density in a Subpopulation of Low-Oxygenated Male Rat Islets
2019 (English)In: Journal of the Endocrine Society, E-ISSN 2472-1972, Vol. 3, no 8, p. 1608-1616Article in journal (Refereed) Published
Abstract [en]

Low-oxygenated and dormant islets with a capacity to become activated when neededmay play a crucial role in the complex machinery behind glucose homeostasis. We hypothesized that low-oxygenated islets, when not functionally challenged, do not rapidly cycle between activation and inactivation but are a stable population that remain low-oxygenated. As this was confirmed, we aimed to characterize these islets with regard to cell composition, vascular density, and endocrine cell proliferation. The 2-nitroimidazole low-oxygenation marker pimonidazole was administered as a single or repeated dose to Wistar Furth rats. The stability of oxygen status of islets was evaluated by immunohistochemistry as the number of islets with incorporated pimonidazole adducts after one or repeated pimonidazole injections. Adjacent sections were evaluated for islet cell composition, vascular density, and endocrine cell proliferation. Single and repeated pimonidazole injections over an 8-hour period yielded accumulation of pimonidazole adducts in the same islets. An average of 30% of all islets was in all cases positively stained for pimonidazole adducts. These islets showed a similar endocrine cell composition as other islets but had lower vascular density and beta-cell proliferation. In conclusion, low-oxygenated islets were found to be a stable subpopulation of islets for at least 8 hours. Although they have previously been observed to be less functionally active, their islet cell composition was similar to that of other islets. Consistent with their lower oxygenation, they had fewer blood vessels than other islets. Notably, beta-cell regeneration preferentially occurred in better-oxygenated islets.

Place, publisher, year, edition, pages
Endocrine Society, 2019
Keywords
islet vasculature, pancreatic islets, heterogeneity, beta-cell proliferation
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-330804 (URN)10.1210/js.2019-00101 (DOI)000484384400015 ()31404404 (PubMedID)
Funder
Swedish Research Council, 55X-15043Swedish Child Diabetes FoundationSwedish Diabetes AssociationEXODIAB - Excellence of Diabetes Research in SwedenNovo Nordisk
Note

Title in thesis list of papers: Decreased beta cell proliferation and vascular density in a subpopulation of low-oxygenated rat islets

Available from: 2017-10-04 Created: 2017-10-04 Last updated: 2019-10-17Bibliographically approved
Drott, C. J., Franzén, P. & Carlsson, P.-O. (2019). Ghrelin in rat pancreatic islets decreases islet blood flow. American Journal of Physiology. Endocrinology and Metabolism, 317(1), E139-E146
Open this publication in new window or tab >>Ghrelin in rat pancreatic islets decreases islet blood flow
2019 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 317, no 1, p. E139-E146Article in journal (Refereed) Published
Abstract [en]

The peptide ghrelin is mainly produced in some of the epithelial cells in the stomach, but also, during starvation, by the epsilon-cells in the endocrine pancreas. Ghrelin, as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R1 alpha). exerts a variety of metabolic functions including stimulation of appetite and weight gain. Its complete role is not yet fully understood, including whether it has any vascular functions. The present study evaluated if ghrelin affects pancreatic and islet blood flow. Ghrelin and the GHS-R1 alpha receptor antagonist GHRP-6 were injected intravenously in rats followed by blood flow measurements using a microsphere technique. Ghrelin decreased, while GHRP-6 in fasted, but not fed, rats selectively increased islet blood flow fourfold. GHS-R1 alpha was identified not only on glucagon-producing cells but also seemed to be present in the islet arterioles. GHRP-6 in fasted rats. only, also improved the peak insulin response to glucose in vivo. thereby substantially blunting the hyperglycemia. GHRP-6 doubled glucose-stimulated insulin release in vitro of both islets obtained from fed and fasted rats. Our results indicate a novel role for endogenous ghrelin acting directly or indirectly as a local vasoconstrictor in the islets during fasting, thereby restricting the insulin response to hyperglycemia. This is to the best of our knowledge the first report that shows this physiological mechanism to restrict insulin delivery from the islets by acting on the vasculature; a mode of action that can be envisaged to complement the previously well-described mechanisms of ghrelin acting directly on the islet endocrine cells.

Keywords
blood flow, ghrelin, pancreatic islets, vascular
National Category
Endocrinology and Diabetes Physiology
Identifiers
urn:nbn:se:uu:diva-390975 (URN)10.1152/ajpendo.00004.2019 (DOI)000475371500005 ()31063397 (PubMedID)
Funder
Swedish Research CouncilEXODIAB - Excellence of Diabetes Research in SwedenSwedish Child Diabetes FoundationSwedish Diabetes AssociationNovo Nordisk
Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2019-08-16Bibliographically approved
Zhou, Y., Li, W., Zhou, J., Chen, J., Wang, X., Cai, M., . . . Sun, Z. (2019). Lipotoxicity reduces beta cell survival through islet stellate cell activation regulated by lipid metabolism-related molecules. Experimental Cell Research, 380(1), 1-8
Open this publication in new window or tab >>Lipotoxicity reduces beta cell survival through islet stellate cell activation regulated by lipid metabolism-related molecules
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2019 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 380, no 1, p. 1-8Article in journal (Refereed) Published
Abstract [en]

Background: Islet stellate cells (ISCs) activation is mainly associated with islet fibrosis, which contributes to the progression of type 2 diabetes. However, the molecular mechanism underlying this process is not fully understood.

Methods: In order to investigate this process the current study examined ectopic fat accumulation in rats with high-fat diet (HFD) induced obesity. Levels of lipotoxicity-induced ISC activation and islet function were assessed via intraperitoneal glucose and insulin tolerance tests, and immunohistochemistry. The expression of lipid metabolism- and ISC activation-related markers was evaluated in cultured ISCs treated with palmitic acid (PA) using quantitative PCR and western blotting. We also overexpressed sterol regulatory element-binding protein (SREBP)-1c in ISCs by lentiviral transduction, and assessed the effects on insulin release in co-cultures with isolated rat islets.

Results: HFD increased body weight and ectopic fat accumulation in pancreatic islets. Lipotoxicity caused progressive glucose intolerance and insulin resistance, upregulated a-smooth muscle actin, and stimulated the secretion of extracellular matrix. Lipotoxicity reduced the expression of lipid metabolism-related molecules in ISCs treated with PA, especially SREBP-1c. Overexpression of SREBP-1c in ISCs improved islet viability and insulin secretion in co-cultures.

Conclucions: These results indicate that lipotoxicity-induced ISC activation alters islet function via regulation of lipid metabolism, suggesting that therapeutic strategies targeting activated ISC may be an effective treatment for prevention of ISC activation-associated islet dysfunction.

Place, publisher, year, edition, pages
ELSEVIER INC, 2019
Keywords
Islet stellate cell, Lipotoxicity, beta cell, Lipid metabolism, SREBP-1c
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-384985 (URN)10.1016/j.yexcr.2019.04.012 (DOI)000468124700001 ()30998947 (PubMedID)
Available from: 2019-06-14 Created: 2019-06-14 Last updated: 2019-06-14Bibliographically approved
Liljebäck, H., Espes, D. & Carlsson, P.-O. (2019). Unsurpassed Intrahepatic Islet Engraftment: the Quest for New Sites for Beta Cell Replacement. Cell Medicine, 11, Article ID 2155179019857662.
Open this publication in new window or tab >>Unsurpassed Intrahepatic Islet Engraftment: the Quest for New Sites for Beta Cell Replacement
2019 (English)In: Cell Medicine, ISSN 2155-1790, E-ISSN 2155-1790, Vol. 11, article id 2155179019857662Article in journal, Editorial material (Other academic) Published
Abstract [en]

The liver is currently the site of choice for clinical islet transplantation, even though many alternative implantation sites have lately been proposed as more ideal for graft survival. The suggested sites, for example intramuscular space, omentum, bone marrow, and spleen, are sometimes difficult to compare due to differences in animal model, islet isolation procedure, and islet quality. In addition, the variation in transplanted islet mass is vast. The aim of this commentary is to review alternative implantation sites tested experimentally as well as in clinical islet transplantation. Although many sites have been investigated, none have convincingly proved better suited for clinical islet transplantation than intraportal injection to the liver, regardless of whether it is autologous or allogeneic transplantation. However, in order to fully evaluate upcoming bioengineering techniques, such as scaffolds containing insulin-producing cells derived from stem cells, the need of an alternative site has arisen to enable cellular monitoring, which currently cannot be achieved within the liver.

Place, publisher, year, edition, pages
Sage Publications, 2019
Keywords
intraportal islet transplantation, type 1 diabetes, beta cell replacement
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-390334 (URN)10.1177/2155179019857662 (DOI)000472913100001 ()
Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-08-09Bibliographically approved
Grapensparr, L., Christoffersson, G. & Carlsson, P.-O. (2018). Bioengineering with Endothelial Progenitor Cells Improves the Vascular Engraftment of Transplanted Human Islets. Cell Transplantation, 27(6), 948-956
Open this publication in new window or tab >>Bioengineering with Endothelial Progenitor Cells Improves the Vascular Engraftment of Transplanted Human Islets
2018 (English)In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 27, no 6, p. 948-956Article in journal (Refereed) Published
Abstract [en]

Pancreatic islets isolated for transplantation are disconnected from their vascular supply and need to establish a new functional network posttransplantation. Due to poor revascularization, prevailing hypoxia with correlating increased apoptosis rates in experimental studies can be observed for months posttransplantation. Endothelial progenitor cells (EPCs) are bone marrow-derived cells that promote neovascularization. The present study tested the hypothesis that EPCs, isolated from human umbilical cord blood, could be coated to human islet surfaces and be used to promote islet vascular engraftment. Control or EPC bioengineered human islets were transplanted into the renal subcapsular space of nonobese diabetic/severe combined immunodeficiency mice. Four weeks posttransplantation, graft blood perfusion and oxygen tension were measured using laser Doppler flowmetry and Clark microelectrodes, respectively. Vessel functionality was also assessed by in vivo confocal imaging. The vascular density and the respective contribution of human and recipient endothelium were assessed immunohistochemically by staining for human and mouse CD31. Islet grafts with EPCs had substantially higher blood perfusion and oxygen tension than control transplants. Furthermore, analysis of the vascular network of the grafts revealed that grafts containing EPC bioengineered islets had a superior vascular density compared with control grafts, with functional chimeric blood vessels. We conclude that a simple procedure of surface coating with EPCs provides a possibility to improve the vascular engraftment of transplanted human islets. Established protocols are also easily applicable for intraportal islet transplantation in order to obtain a novel directed cellular therapy at the site of implantation in the liver.

Keywords
endothelial progenitor cells, islet revascularization, neovascularization, islet engraftment
National Category
Surgery Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-361553 (URN)10.1177/0963689718759474 (DOI)000438945100009 ()29862837 (PubMedID)
Funder
Swedish Research CouncilSwedish Child Diabetes FoundationSwedish Diabetes AssociationEXODIAB - Excellence of Diabetes Research in SwedenTorsten Söderbergs stiftelseNovo NordiskStiftelsen Olle Engkvist ByggmästareAFA Insurance
Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2018-10-08Bibliographically approved
Rasouli, B., Ahlqvist, E., Alfredsson, L., Andersson, T., Carlsson, P.-O., Groop, L., . . . Carlsson, S. (2018). Coffee consumption, genetic susceptibility and risk of latent autoimmune diabetes in adults: A population-based case-control study.. Diabetes & Metabolism, 44(4), 354-360, Article ID S1262-3636(18)30087-9.
Open this publication in new window or tab >>Coffee consumption, genetic susceptibility and risk of latent autoimmune diabetes in adults: A population-based case-control study.
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2018 (English)In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 44, no 4, p. 354-360, article id S1262-3636(18)30087-9Article in journal (Refereed) Published
Abstract [en]

AIM: Coffee consumption is inversely related to risk of type 2 diabetes (T2D). In contrast, an increased risk of latent autoimmune diabetes in adults (LADA) has been reported in heavy coffee consumers, primarily in a subgroup with stronger autoimmune characteristics. Our study aimed to investigate whether coffee consumption interacts with HLA genotypes in relation to risk of LADA.

METHODS: This population-based study comprised incident cases of LADA (n=484) and T2D (n=1609), and also 885 healthy controls. Information on coffee consumption was collected by food frequency questionnaire. Odds ratios (ORs) with 95% CIs of diabetes were calculated and adjusted for age, gender, BMI, education level, smoking and alcohol intake. Potential interactions between coffee consumption and high-risk HLA genotypes were calculated by attributable proportion (AP) due to interaction.

RESULTS: Coffee intake was positively associated with LADA in carriers of high-risk HLA genotypes (OR: 1.14 per cup/day, 95% CI: 1.02-1.28), whereas no association was observed in non-carriers (OR: 1.04, 95% CI: 0.93-1.17). Subjects with both heavy coffee consumption (≥4 cups/day) and high-risk HLA genotypes had an OR of 5.74 (95% CI: 3.34-9.88) with an estimated AP of 0.36 (95% CI: 0.01-0.71; P=0.04370).

CONCLUSION: Our findings suggest that coffee consumption interacts with HLA to promote LADA.

Keywords
Autoimmune diabetes, Coffee consumption, Gene–environmental interaction, LADA, Latent autoimmune diabetes in adults, Type 2 diabetes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-368173 (URN)10.1016/j.diabet.2018.05.002 (DOI)000447960300007 ()29861145 (PubMedID)
Available from: 2018-12-04 Created: 2018-12-04 Last updated: 2018-12-10Bibliographically approved
Medina, A., Parween, S., Ullsten, S., Vishnu, N., Siu, Y. T., Quach, M., . . . Fex, M. (2018). Early deficits in insulin secretion, beta cell mass and islet blood perfusion precede onset of autoimmune type 1 diabetes in BioBreeding rats. Diabetologia, 61(4), 896-905
Open this publication in new window or tab >>Early deficits in insulin secretion, beta cell mass and islet blood perfusion precede onset of autoimmune type 1 diabetes in BioBreeding rats
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2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 4, p. 896-905Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis Genetic studies show coupling of genes affecting beta cell function to type 1 diabetes, but hitherto no studies on whether beta cell dysfunction could precede insulitis and clinical onset of type 1 diabetes are available. Methods We used 40-day-old BioBreeding (BB) DRLyp/Lyp rats (a model of spontaneous autoimmune type 1 diabetes) and diabetes-resistant DRLyp/+ and DR+/+ littermates (controls) to investigate beta cell function in vivo, and insulin and glucagon secretion in vitro. Beta cell mass was assessed by optical projection tomography (OPT) and morphometry. Additionally, measurements of intra-islet blood flow were performed using microsphere injections. We also assessed immune cell infiltration, cytokine expression in islets (by immunohistochemistry and qPCR), as well as islet Glut2 expression and ATP/ADP ratio to determine effects on glucose uptake and metabolism in beta cells. Results DRLyp/Lyp rats were normoglycaemic and without traces of immune cell infiltrates. However, IVGTTs revealed a significant decrease in the acute insulin response to glucose compared with control rats (1685.3 +/- 121.3 vs 633.3 +/- 148.7; p < 0.0001). In agreement, insulin secretion was severely perturbed in isolated islets, and both first- and second-phase insulin release were lowered compared with control rats, while glucagon secretion was similar in both groups. Interestingly, after 5-7 days of culture of islets from DRLyp/Lyp rats in normal media, glucose-stimulated insulin secretion (GSIS) was improved; although, a significant decrease in GSIS was still evident compared with islets from control rats at this time (7393.9 +/- 1593.7 vs 4416.8 +/- 1230.5 pg islet(-1) h(-1); p < 0.0001). Compared with controls, OPT of whole pancreas from DRLyp/Lyp rats revealed significant reductions in medium (4.1 x 10(9) +/- 9.5 x 10(7) vs 3.8 x 10(9) +/- 5.8 x 10(7) mu m(3); p = 0.044) and small sized islets (1.6 x 10(9) +/- 5.1 x 10(7) vs 1.4 x 10(9) +/- 4.5 x 10(7) mu m(3); p = 0.035). Finally, we found lower intra-islet blood perfusion in vivo (113.1 +/- 16.8 vs 76.9 +/- 11.8 mu l min(-1) [g pancreas](-1); p = 0.023) and alterations in the beta cell ATP/ADP ratio in DRLyp/Lyp rats vs control rats. Conclusions/interpretation The present study identifies a deterioration of beta cell function and mass, and intra-islet blood flow that precedes insulitis and diabetes development in animals prone to autoimmune type 1 diabetes. These underlying changes in islet function may be previously unrecognised factors of importance in type 1 diabetes development.

Place, publisher, year, edition, pages
SPRINGER, 2018
Keywords
Beta cell dysfunction, Beta cell mass, Insulin secretion, Islet blood flow, Type 1 diabetes
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-350274 (URN)10.1007/s00125-017-4512-z (DOI)000427049100017 ()29209740 (PubMedID)
Funder
Novo NordiskThe Crafoord FoundationSwedish Research Council, K2013-99X-22212-01-5, K2016-01495_3, K2011-54X-15312-07-6, K2013-55X-15043-10-5
Available from: 2018-05-14 Created: 2018-05-14 Last updated: 2018-05-14Bibliographically approved
Herrera Hidalgo, C., Ullsten, S., Vågesjö, E., Parv, K., Liu, H., Giraud, A., . . . Phillipson, M. (2018). Effect of neonatal infections on pancreatic macrophages, islet development and long-term glucose homeostasis. Paper presented at 52nd Annual Scientific Meeting of the European Society for Clinical Investigation “Precision medicine for healthy ageing”, 30th May – 1st June 2018, Barcelona, Spain.. European Journal of Clinical Investigation, 48(S1), 83-83
Open this publication in new window or tab >>Effect of neonatal infections on pancreatic macrophages, islet development and long-term glucose homeostasis
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2018 (English)In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 48, no S1, p. 83-83Article in journal, Meeting abstract (Other academic) Published
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-366628 (URN)10.1111/eci.12926 (DOI)000434100200185 ()
Conference
52nd Annual Scientific Meeting of the European Society for Clinical Investigation “Precision medicine for healthy ageing”, 30th May – 1st June 2018, Barcelona, Spain.
Note

Meeting Abstract: P032-T

Available from: 2018-11-23 Created: 2018-11-23 Last updated: 2018-12-11Bibliographically approved
Bhandage, A., Jin, Z., Korol, S. V., Tafreshiha, A., Gohel, P., Hellgren, C., . . . Birnir, B. (2018). Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes. PLoS ONE, 13(12), Article ID e0208981.
Open this publication in new window or tab >>Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0208981Article in journal (Refereed) Published
Abstract [en]

Calcium (Ca2+) is an important ion in physiology and is found both outside and inside cells. The intracellular concentration of Ca2+ is tightly regulated as it is an intracellular signal molecule and can affect a variety of cellular processes. In immune cells Ca2+ has been shown to regulate e.g. gene transcription, cytokine secretion, proliferation and migration. Ca2+ can enter the cytoplasm either from intracellular stores or from outside the cells when Ca2+ permeable ion channels in the plasma membrane open. The Ca2+ release-activated (CRAC) channel is the most prominent Ca2+ ion channel in the plasma membrane. It is formed by ORAI1-3 and the channel is opened by the endoplasmic reticulum Ca2+ sensor proteins stromal interaction molecules (STIM) 1 and 2. Another group of Ca-2(+) channels in the plasma membrane are the voltage-gated Ca2+ (Ca-V) channels. We examined if a change in immunological tolerance is accompanied by altered ORAI, STIM and Ca-V gene expression in peripheral blood mononuclear cells (PBMCs) in pregnant women and in type 1 diabetic individuals. Our results show that in pregnancy and type 1 diabetes ORAI1-3 are up-regulated whereas STIM1 and 2 are down-regulated in pregnancy but only STIM2 in type 1 diabetes. Expression of L-, P/Q-, R- and T-type voltage-gated Ca2+ channels was detected in the PBMCs where the Ca(V)2.3 gene was up-regulated in pregnancy and type 1 diabetes whereas the Ca(V)2.1 and Ca(V)3.2 genes were up-regulated only in pregnancy and the Ca(V)1.3 gene in type 1 diabetes. The results are consistent with that expression of ORAI, STIM and Ca-V genes correlate with a shift in immunological status of the individual in health, as during pregnancy, and in the autoimmune disease type 1 diabetes. Whether the changes are in general protective or in type 1 diabetes include some pathogenic components remains to be clarified.

National Category
Endocrinology and Diabetes Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-372929 (URN)10.1371/journal.pone.0208981 (DOI)000453247500057 ()30543678 (PubMedID)
Funder
Swedish Research CouncilEXODIAB - Excellence of Diabetes Research in SwedenSwedish Diabetes AssociationSwedish Child Diabetes FoundationErnfors Foundation
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-01-10Bibliographically approved
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