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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
Öppna denna publikation i ny flik eller fönster >>Decreased beta-Cell Proliferation and Vascular Density in a Subpopulation of Low-Oxygenated Male Rat Islets
2019 (Engelska)Ingår i: Journal of the Endocrine Society, E-ISSN 2472-1972, Vol. 3, nr 8, s. 1608-1616Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Endocrine Society, 2019
Nyckelord
islet vasculature, pancreatic islets, heterogeneity, beta-cell proliferation
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:uu:diva-330804 (URN)10.1210/js.2019-00101 (DOI)000484384400015 ()31404404 (PubMedID)
Forskningsfinansiär
Vetenskapsrådet, 55X-15043BarndiabetesfondenDiabetesförbundetEXODIAB - Excellence of Diabetes Research in SwedenNovo Nordisk
Anmärkning

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

Tillgänglig från: 2017-10-04 Skapad: 2017-10-04 Senast uppdaterad: 2019-10-17Bibliografiskt granskad
Liljebäck, H., Quach, M., Carlsson, P.-O. & Lau, J. (2019). Fewer Islets Survive from a First Transplant than a Second Transplant: Evaluation of Repeated Intraportal Islet Transplantation in Mice. Cell Transplantation, 28(11), 1455-1460
Öppna denna publikation i ny flik eller fönster >>Fewer Islets Survive from a First Transplant than a Second Transplant: Evaluation of Repeated Intraportal Islet Transplantation in Mice
2019 (Engelska)Ingår i: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 28, nr 11, s. 1455-1460Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Beta cell replacement is an exciting field where new beta cell sources and alternative sites are widely explored. The liver has been the implantation site of choice in the clinic since the advent of islet transplantation. However, in most cases, repeated islet transplantation is needed to achieve normoglycemia in diabetic recipients. This study aimed to investigate whether there are differences in islet survival and engraftment between a first and a second transplantation, performed 1 week apart, to the liver. C57BL/6 mice were accordingly transplanted twice with an initial infusion of syngeneic islets expressing green fluorescent protein (GFP). The second islet transplant was performed 1 week later and consisted of islets isolated from non-GFP C57BL/6-mice. Animals were sacrificed either 1 day or 1 month after the second transplantation. A control group received a saline infusion instead of GFP-expressing islets, 1 week later obtained a standard non-GFP islet transplant, and was subsequently sacrificed 1 month later. Islet engraftment in the liver was assessed by immunohistochemistry and serum was analyzed for angiogenic factors induced by the first islet transplantation. Almost 70% of islets found in the liver following repeated islet transplantation originated from the second transplantation. The vascular density in the transplanted non-GFP-expressing islets did not differ depending on whether their transplantation was preceded by a primary islet transplantation or saline administration only nor did angiogenic factors in serum prior to the transplantation of non-GFP islets differ between animals that had received a previous islet transplantation or a saline infusion. We conclude that first islet transplantation creates, by unknown mechanisms, favorable conditions for the survival of a second transplant to the liver.

Nyckelord
GFP, engraftment, islet transplantation, type 1 diabetes
Nationell ämneskategori
Cell- och molekylärbiologi
Identifikatorer
urn:nbn:se:uu:diva-398599 (URN)10.1177/0963689719866685 (DOI)000479643300001 ()31359771 (PubMedID)
Forskningsfinansiär
BarndiabetesfondenVetenskapsrådet, 2017-01343EXODIAB - Excellence of Diabetes Research in SwedenDiabetesförbundet
Tillgänglig från: 2019-12-07 Skapad: 2019-12-07 Senast uppdaterad: 2020-01-17Bibliografiskt granskad
Shi, R., Hu, J., Li, W., Wang, Z., Pan, Y., Bai, M., . . . Zhao, S. (2019). Protective effects of Clec11a in islets against lipotoxicity via modulation of proliferation and lipid metabolism in mice. Experimental Cell Research, 384(1), Article ID 111613.
Öppna denna publikation i ny flik eller fönster >>Protective effects of Clec11a in islets against lipotoxicity via modulation of proliferation and lipid metabolism in mice
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2019 (Engelska)Ingår i: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 384, nr 1, artikel-id 111613Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The lipotoxicity is considered as one of the risk for diabetes. Here we report C-type lectin domain family 11, member A (Clec11a) as a new regulator in islet playing a protective role in lipotoxicity induced dysfunction. Islet transcriptome sequencing was performed using the high-fat diet induced obesity (DIO) mice model. We found a significant decrease of Clec11a expression in islets of DIO mice compared to normal control mice, which was further confirmed by real-time PCR. Immunostaining demonstrated the localization of the Clec11a protein in mouse islets. Administration of recombinant human Clec11a (rClec11a) protein promoted the proliferation of islet cells and rescued the inhibition of fatty acid on cell proliferation, which involved the activation of Erk signaling pathway. We also found that the rClec11a altered the expression of genes involved in lipid metabolism.

Ort, förlag, år, upplaga, sidor
ELSEVIER INC, 2019
Nyckelord
Clec11a, Beta cell, Islet, Lipotoxicity, Proliferation
Nationell ämneskategori
Endokrinologi och diabetes Cell- och molekylärbiologi
Identifikatorer
urn:nbn:se:uu:diva-396433 (URN)10.1016/j.yexcr.2019.111613 (DOI)000490031700016 ()31494095 (PubMedID)
Tillgänglig från: 2019-11-06 Skapad: 2019-11-06 Senast uppdaterad: 2019-11-06Bibliografiskt granskad
Pereira, M. J., Lundkvist, P., Kamble, P. G., Lau, J., Martins, J. G., Sjostrom, C. D., . . . Eriksson, J. W. (2018). A Randomized Controlled Trial of Dapagliflozin Plus Once-Weekly Exenatide Versus Placebo in Individuals with Obesity and Without Diabetes: Metabolic Effects and Markers Associated with Bodyweight Loss. Diabetes Therapy, 9(4), 1511-1532
Öppna denna publikation i ny flik eller fönster >>A Randomized Controlled Trial of Dapagliflozin Plus Once-Weekly Exenatide Versus Placebo in Individuals with Obesity and Without Diabetes: Metabolic Effects and Markers Associated with Bodyweight Loss
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2018 (Engelska)Ingår i: Diabetes Therapy, ISSN 1869-6953, E-ISSN 1869-6961, Vol. 9, nr 4, s. 1511-1532Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The sodium-glucose cotransporter 2 inhibitor dapagliflozin and the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduce bodyweight via differing and complementary mechanisms. This post hoc analysis investigated the metabolic effects and baseline associations with bodyweight loss on coadministration of dapagliflozin and exenatide once weekly (QW) among adults with obesity and without diabetes. In the primary trial, adults with obesity and without diabetes [n = 50; 18-70 years; body mass index (BMI) 30-45 kg/m(2)] were randomized to double-blind oral dapagliflozin 10 mg (DAPA) once daily plus subcutaneous long-acting exenatide 2 mg QW (ExQW) or placebo over 24 weeks, followed by an open-label extension from 24-52 weeks during which all participants received active treatment. Primary results have been published previously. This analysis evaluated: (1) the effects of DAPA + ExQW on changes in substrates [free fatty acids (FFAs), glycerol, beta-OH-butyrate, and glucose], hormones (glucagon and insulin), and insulin secretion [insulinogenic index (IGI)] via an oral glucose tolerance test (OGTT) and (2) associations between bodyweight loss and baseline characteristics (e.g., BMI), single-nucleotide polymorphisms (SNPs) associated with the GLP-1 pathway, and markers of glucose regulation. Compared with placebo at 24 weeks, 2-h FFAs post-OGTT increased (mean difference, +20.4 mu mol/l; P < 0.05), and fasting glucose, 2-h glucose post-OGTT, and glucose area under the concentration-time curve (AUC) decreased with DAPA + ExQW [mean differences, -0.68 mmol/l [P < 0.001], -2.20 mmol/l (P < 0.01), and -306 mmol/l min (P < 0.001), respectively]. Glucagon, glycerol, beta-OH-butyrate, and IGI did not differ by treatment group at 24 weeks. Over 52 weeks, DAPA + ExQW decreased fasting insulin, 2-h post-OGTT insulin, and insulin AUC. Among DAPA + ExQW-treated participants, for each copy of the SNP variant rs10010131 A allele (gene WFS1), bodyweight decreased by 2.4 kg (P < 0.05). Lower BMI and a lower IGI were also associated with greater bodyweight loss with DAPA + ExQW. Metabolic effects with DAPA + ExQW included less FFA suppression versus placebo during the OGTT, suggesting compensatory lipid mobilization for energy production when glucose availability was reduced because of glucosuria. The expected increase in glucagon with DAPA did not occur with DAPA + ExQW coadministration. Bodyweight loss with DAPA + ExQW was associated with the SNP variant rs10010131 A allele, lower baseline adiposity (BMI), and lower baseline insulin secretion (IGI). These findings require further validation. AstraZeneca.

Ort, förlag, år, upplaga, sidor
Springer Berlin/Heidelberg, 2018
Nyckelord
Dapagliflozin, Exenatide, Lipid metabolism, Obesity, Single-nucleotide polymorphism, Weight loss
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:uu:diva-362039 (URN)10.1007/s13300-018-0449-6 (DOI)000440115700010 ()29949016 (PubMedID)
Forskningsfinansiär
AstraZeneca
Tillgänglig från: 2018-10-12 Skapad: 2018-10-12 Senast uppdaterad: 2018-10-12Bibliografiskt granskad
Boersma, G. J., Johansson, E., Pereira, M. J., Heurling, K., Skrtic, S., Lau, J., . . . Eriksson, J. (2018). Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study. Hormone and Metabolic Research, 50(8), 627-639
Öppna denna publikation i ny flik eller fönster >>Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study
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2018 (Engelska)Ingår i: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 50, nr 8, s. 627-639Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

We assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body 18F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues. MRglu in skeletal muscle, SAT, visceral adipose tissue (VAT), and liver was significantly reduced in T2D subjects and correlated positively with M-values (r=0.884, r=0.574, r=0.707 and r=0.403, respectively). Brain MRglu was significantly higher in T2D and prediabetes subjects and had a significant inverse correlation with M-values (r=-0.616). Myocardial MRglu did not differ between groups and did not correlate with the M-values. A multivariate model including skeletal muscle, brain and VAT MRglu best predicted the M-values (adjusted r2=0.85). In addition, SAT MRglu correlated with SAT glucose uptake ex vivo (r=0.491). In different stages of the development of T2D, glucose uptake during hyperinsulinemia is elevated in the brain in parallel with an impairment in peripheral organs. Impaired glucose uptake in skeletal muscle and VAT together with elevated glucose uptake in brain were independently associated with whole-body insulin resistance, and these tissue-specific alterations may contribute to T2D development.

Ort, förlag, år, upplaga, sidor
Georg Thieme Verlag KG, 2018
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:uu:diva-356788 (URN)10.1055/a-0643-4739 (DOI)000440872200007 ()30001566 (PubMedID)
Forskningsfinansiär
AstraZenecaEXODIAB - Excellence of Diabetes Research in SwedenDiabetesförbundetVetenskapsrådetStiftelsen familjen Ernfors fond
Tillgänglig från: 2018-08-07 Skapad: 2018-08-07 Senast uppdaterad: 2018-11-08Bibliografiskt granskad
Monazzam, A., Lau, J., Velikyan, I., Li, S.-C., Razmara, M., Rosenström, U., . . . Skogseid, B. (2018). Increased Expression of GLP-1R in Proliferating Islets of Men1 Mice is Detectable by [Ga-68]Ga-DO3A-VS-Cys(40)- Exendin-4/PET. Scientific Reports, 8, Article ID 748.
Öppna denna publikation i ny flik eller fönster >>Increased Expression of GLP-1R in Proliferating Islets of Men1 Mice is Detectable by [Ga-68]Ga-DO3A-VS-Cys(40)- Exendin-4/PET
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2018 (Engelska)Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 748Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of the adolescent gene carrier frequently contain diffusely spread pre-neoplasias and microadenomas, progressing to macroscopic and potentially malignant pancreatic neuroendocrine tumors (P-NET), which represents the major death cause in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently understood fully to allow the optimization of diagnostics and treatment. Glucagon-like peptide 1 (GLP-1) pathway is essential in islet regeneration, i.e. inhibition of β-cell apoptosis and enhancement of β-cell proliferation, yet involvement of GLP-1 in MEN1 related P-NET has not yet been demonstrated. The objective of this work was to investigate if normal sized islets of Men1 heterozygous mice have increased Glucagon-like peptide-1 receptor (GLP-1R) expression compared to wild type islets, and if this increase is detectable in vivo with positron emission tomography (PET) using [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 (68Ga-Exendin-4). 68Ga-Exendin-4 showed potential for early lesion detection in MEN1 pancreas due to increased GLP1R expression.

Nationell ämneskategori
Medicinska och farmaceutiska grundvetenskaper
Identifikatorer
urn:nbn:se:uu:diva-342327 (URN)10.1038/s41598-017-18855-0 (DOI)000422637200007 ()29335487 (PubMedID)
Forskningsfinansiär
Cancerfonden
Tillgänglig från: 2018-02-20 Skapad: 2018-02-20 Senast uppdaterad: 2018-02-28Bibliografiskt granskad
Boersma, G. J., Heurling, K., Pereira, M. J., Johansson, E., Lubberink, M., Lau Börjesson, J., . . . Eriksson, J. W. (2017). Glucose uptake in skeletal muscle, brain and visceral adipose tissue assessed with PET/MR strongly predicts whole body glucose uptake during hyperinsulinaemia. Paper presented at 53rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 11-15, 2017, Lisbon, PORTUGAL. Diabetologia, 60, S80-S80
Öppna denna publikation i ny flik eller fönster >>Glucose uptake in skeletal muscle, brain and visceral adipose tissue assessed with PET/MR strongly predicts whole body glucose uptake during hyperinsulinaemia
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2017 (Engelska)Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, s. S80-S80Artikel i tidskrift, Meeting abstract (Övrigt vetenskapligt) Published
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:uu:diva-346985 (URN)000408315000170 ()
Konferens
53rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 11-15, 2017, Lisbon, PORTUGAL
Tillgänglig från: 2018-03-23 Skapad: 2018-03-23 Senast uppdaterad: 2018-03-23Bibliografiskt granskad
Sidibeh, C. O., Pereira, M. J., Börjesson, J. L., Kamble, P. G., Skrtic, S., Katsogiannos, P., . . . Eriksson, J. W. (2017). Role of cannabinoid receptor 1 in human adipose tissue for lipolysis regulation and insulin resistance. Endocrine (Basingstoke), 55(3), 839-852
Öppna denna publikation i ny flik eller fönster >>Role of cannabinoid receptor 1 in human adipose tissue for lipolysis regulation and insulin resistance
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2017 (Engelska)Ingår i: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 55, nr 3, s. 839-852Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

We recently showed that the peripheral cannabinoid receptor type 1 (CNR1) gene is upregulated by the synthetic glucocorticoid dexamethasone. CNR1 is highly expressed in the central nervous system and has been a drug target for the treatment of obesity. Here we explore the role of peripheral CNR1 in states of insulin resistance in human adipose tissue. Subcutaneous adipose tissue was obtained from well-controlled type 2 diabetes subjects and controls. Subcutaneous adipose tissue gene expression levels of CNR1 and endocannabinoid synthesizing and degrading enzymes were assessed. Furthermore, paired human subcutaneous adipose tissue and omental adipose tissue from non-diabetic volunteers undergoing kidney donation or bariatric surgery, was incubated with or without dexamethasone. Subcutaneous adipose tissue obtained from volunteers through needle biopsy was incubated with or without dexamethasone and in the presence or absence of the CNR1-specific antagonist AM281. CNR1 gene and protein expression, lipolysis and glucose uptake were evaluated. Subcutaneous adipose tissue CNR1 gene expression levels were 2-fold elevated in type 2 diabetes subjects compared with control subjects. Additionally, gene expression levels of CNR1 and endocannabinoid-regulating enzymes from both groups correlated with markers of insulin resistance. Dexamethasone increased CNR1 expression dose-dependently in subcutaneous adipose tissue and omental adipose tissue by up to 25-fold. Dexamethasone pre-treatment of subcutaneous adipose tissue increased lipolysis rate and reduced glucose uptake. Co-incubation with the CNR1 antagonist AM281 prevented the stimulatory effect on lipolysis, but had no effect on glucose uptake. CNR1 is upregulated in states of type 2 diabetes and insulin resistance. Furthermore, CNR1 is involved in glucocorticoid-regulated lipolysis. Peripheral CNR1 could be an interesting drug target in type 2 diabetes and dyslipidemia.

Ort, förlag, år, upplaga, sidor
SPRINGER, 2017
Nyckelord
Type 2 diabetes, Glucocorticoids, Insulin resistance, Adipose tissue, Endocannabinoid system
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:uu:diva-320351 (URN)10.1007/s12020-016-1172-6 (DOI)000394966900021 ()27858284 (PubMedID)
Forskningsfinansiär
AstraZenecaHjärt-Lungfonden, 20100648Diabetesförbundet
Tillgänglig från: 2017-04-19 Skapad: 2017-04-19 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
Aresh, B., Freitag, F. B., Perry, S., Blümel, E., Lau, J., Franck, M. C. .. & Lagerström, M. C. (2017). Spinal Cord Interneurons Expressing the Gastrin-Releasing Peptide Receptor Convey Itch Through VGLUT2-Mediated Signaling. Pain, 158(5), 945-961
Öppna denna publikation i ny flik eller fönster >>Spinal Cord Interneurons Expressing the Gastrin-Releasing Peptide Receptor Convey Itch Through VGLUT2-Mediated Signaling
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2017 (Engelska)Ingår i: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 158, nr 5, s. 945-961Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Itch is a sensation that promotes the desire to scratch, which can be evoked by mechanical and chemical stimuli. In the spinal cord, neurons expressing the gastrin-releasing peptide receptor (GRPR) have been identified as specific mediators of itch. However, our understanding of the GRPR population in the spinal cord, and thus how these neurons exercise their functions, is limited. For this purpose, we constructed a Cre line designed to target the GRPR population of neurons (Grpr-Cre). Our analysis revealed that Grpr-Cre cells in the spinal cord are predominantly excitatory interneurons that are found in the dorsal lamina, especially in laminae II-IV. Application of the specific agonist gastrin-releasing peptide induced spike responses in 43.3% of the patched Grpr-Cre neurons, where the majority of the cells displayed a tonic firing property. Additionally, our analysis showed that the Grpr-Cre population expresses Vglut2 mRNA, and mice ablated of Vglut2 in Grpr-Cre cells (Vglut2-lox; Grpr-Cre mice) displayed less spontaneous itch and attenuated responses to both histaminergic and nonhistaminergic agents. We could also show that application of the itch-inducing peptide, natriuretic polypeptide B, induces calcium influx in a subpopulation of Grpr-Cre neurons. To summarize, our data indicate that the Grpr-Cre spinal cord neural population is composed of interneurons that use VGLUT2-mediated signaling for transmitting chemical and spontaneous itch stimuli to the next, currently unknown, neurons in the labeled line of itch.

Nyckelord
Itch, Gastrin-releasing peptide receptor population, Natriuretic polypeptide B, Spinal cord, Vesicular glutamate transporter 2, Neuronal networks, Labeled line of itch, Electrophysiology, Conditional knockout analysis, Tracing, Calcium imaging, Grpr, VGLUT2
Nationell ämneskategori
Medicin och hälsovetenskap
Forskningsämne
Medicinsk vetenskap
Identifikatorer
urn:nbn:se:uu:diva-284058 (URN)10.1097/j.pain.0000000000000861 (DOI)000402430600021 ()28157737 (PubMedID)
Forskningsfinansiär
VetenskapsrådetHjärnfondenKungliga VetenskapsakademienRagnar Söderbergs stiftelseMagnus Bergvalls StiftelseGunvor och Josef Anérs stiftelse
Anmärkning

Title in thesis list of papers: Spinal Cord Interneurons Expressing the Gastrin Releasing Peptide Receptor Convey Itch through VGLUT2-mediated Signaling

Tillgänglig från: 2016-04-14 Skapad: 2016-04-14 Senast uppdaterad: 2020-02-03Bibliografiskt granskad
Espes, D., Lau, J. & Carlsson, P.-O. (2017). Towards the clinical translation of stem cell therapy for type 1 diabetes. European Journal of Endocrinology, 177(4), R159-R168
Öppna denna publikation i ny flik eller fönster >>Towards the clinical translation of stem cell therapy for type 1 diabetes
2017 (Engelska)Ingår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 177, nr 4, s. R159-R168Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

Insulin-producing cells derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) have for long been a promising, but elusive treatment far from clinical translation into type 1 diabetes therapy. However, the field is now on the verge of moving such insulin-producing cells into clinical trials. Although stem cell therapies provide great opportunities, there are also potential risks such as teratoma formation associated with the treatment. Many considerations are needed on how to proceed with clinical translation, including whether to use hESCs or iPSCs, and whether encapsulation of tissue will be needed. This review aims to give an overview of the current knowledge of stem cell therapy outcomes in animal models of type 1 diabetes and a proposed road map towards the clinical setting with special focus on the potential risks and hurdles which needs to be considered. From a clinical point of view, transplantation of insulin-producing cells derived from stem cells must be performed without immune suppression in order to be an attractive treatment option. Although costly and highly labour intensive, patient-derived iPSCs would be the only solution, if not clinically successful encapsulation or tolerance induction protocols are introduced.

Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:uu:diva-346616 (URN)10.1530/EJE-17-0080 (DOI)000414730300001 ()28487297 (PubMedID)
Tillgänglig från: 2018-03-21 Skapad: 2018-03-21 Senast uppdaterad: 2018-03-21Bibliografiskt granskad
Organisationer
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0002-8302-3253

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