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Sandberg, Monica
Publications (10 of 25) Show all publications
Gao, X., Lindqvist, A., Sandberg, M., Groop, L., Wierup, N. & Jansson, L. (2018). Effects of GIP on regional blood flow during normoglycemia and hyperglycemia in anesthetized rats. Physiological Reports, 6(8), Article ID e13685.
Open this publication in new window or tab >>Effects of GIP on regional blood flow during normoglycemia and hyperglycemia in anesthetized rats
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2018 (English)In: Physiological Reports, E-ISSN 2051-817X, Vol. 6, no 8, article id e13685Article in journal (Refereed) Published
Abstract [en]

The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-stimulated insulin secretion, and affects -cell turnover. This study aimed at evaluating if some of the beneficial effects of GIP on glucose homeostasis can be explained by modulation of islet blood flow. Anesthetized Sprague-Dawley rats were infused intravenously with different doses of GIP (10, 20, or 60ng/kg*min) for 30min. Subsequent organ blood flow measurements were performed with microspheres. In separate animals, islets were perfused exvivo with GIP (10(-6)-10(-12)mol/L) during normo- and hyperglycemia and arteriolar responsiveness was recorded. The highest dose of GIP potentiated insulin secretion during hyperglycemia, but had no effect in normoglycemic rats. The highest GIP concentration decreased blood perfusion of whole pancreas, pancreatic islets, duodenum, colon, liver and kidneys. The decrease in blood flow was unaffected by ganglion blockade or adenosine receptor inhibition. In contrast to this, in single perfused islets GIP induced a dose-dependent arteriolar dilation. Thus, high doses of GIP exert a direct dilatory effect on islet arterioles in isolated islets, but induce a generalized vasoconstriction in splanchnic organs, including the whole pancreas and islets, invivo. The latter effect is unlikely to be mediated by adenosine, the autonomic nervous system, or endothelial mediators.

Keywords
Glucose-dependent insulinotropic peptide, incretin hormones, Islet blood flow, pancreatic islets, splanchnic blood flow
National Category
Physiology Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-354242 (URN)10.14814/phy2.13685 (DOI)000430922300017 ()29673130 (PubMedID)
Funder
Swedish Research Council, 521-2011-3777Swedish Research Council, 2008-4216Swedish Research Council, 521-2012-2119
Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2018-06-19Bibliographically approved
Li, W., Xie, B., Qiu, S., Huang, X., Chen, J., Wang, X., . . . Sun, Z. (2018). Non-lab and semi-lab algorithms for screening undiagnosed diabetes: A cross-sectional study. EBioMedicine, 35, 307-316
Open this publication in new window or tab >>Non-lab and semi-lab algorithms for screening undiagnosed diabetes: A cross-sectional study
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2018 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 35, p. 307-316Article in journal (Refereed) Published
Abstract [en]

Background: The terrifying undiagnosed rate and high prevalence of diabetes have become a public emergency. A high efficiency and cost-effective early recognition method is urgently needed. We aimed to generate innovative, user-friendly nomograms that can be applied for diabetes screening in different ethnic groups in China using the non-lab or noninvasive semi-lab data. Methods: This multicenter, multi-ethnic, population-based, cross-sectional study was conducted in eight sites in China by enrolling subjects aged 20-70. Sociodemographic and anthropometric characteristics were collected. Blood and urine samples were obtained 2 h following a standard 75 g glucose solution. In the final analysis, 10,794 participants were included and randomized into model development (n - 8096) and model validation (n = 2698) group with a ratio of 3:1. Nomograms were developed by the stepwise binary logistic regression. The nomograms were validated internally by a bootstrap sampling method in the model development set and externally in the model validation set. The area under the receiver operating characteristic curve (AUC) was used to assess the screening performance of the nomograms. Decision curve analysis was applied to calculate the net benefit of the screening model. Results: The overall prevalence of undiagnosed diabetes was 9.8% (1059/10794) according to ADA criteria. The non-lab model revealed that gender, age, body mass index, waist circumference, hypertension, ethnicities, vegetable daily consumption and family history of diabetes were independent risk factors for diabetes. By adding 2 h post meal glycosuria qualitative to the non-lab model, the semi-lab model showed an improved Akaike information criterion (AIC: 4506 to 3580). The AUC of the semi-lab model was statistically larger than the non-lab model (0.868 vs 0.763, P < 0.001). The optimal cutoff probability in semi-lab and non-lab nomograms were 0.088 and 0.098, respectively. The sensitivity and specificity were 76.3% and 81.6%, respectively in semi-lab nomogram, and 72.1% and 673% in non-lab nomogram at the optimal cut off point. The decision curve analysis also revealed a bigger decrease of avoidable OGTT test (52 per 100 subjects) in the semi-lab model compared to the non-lab model (36 per 100 subjects) and the existed New Chinese Diabetes Risk Score (NCDRS, 35 per 100 subjects). Conclusion: The non-lab and semi-lab nomograms appear to be reliable tools for diabetes screening, especially in developing countries. However, the semi-lab model outperformed the non-lab model and NCDRS prediction systems and might be worth being adopted as decision support in diabetes screening in China.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2018
Keywords
Diabetes, Nomogram, Decision curve, Risk algorithm
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-363628 (URN)10.1016/j.ebiom.2018.08.009 (DOI)000445436400044 ()30115607 (PubMedID)
Available from: 2018-10-25 Created: 2018-10-25 Last updated: 2018-10-25Bibliographically approved
Sandberg, M., Johansson, S., Sagulin, L., Jansson, L. & Johansson, S. (2017). Scavenging Endothelium of Pancreatic Islets Differential Expression of Stabilin-1 and Stabilin-2 in Mice and Humans [Letter to the editor]. Pancreas, 46(1), E4-E5
Open this publication in new window or tab >>Scavenging Endothelium of Pancreatic Islets Differential Expression of Stabilin-1 and Stabilin-2 in Mice and Humans
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2017 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 46, no 1, p. E4-E5Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2017
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-321001 (URN)10.1097/MPA.0000000000000709 (DOI)000397644300005 ()27977633 (PubMedID)
Funder
Swedish Research Council, 521-2011-3777, 7147EXODIAB - Excellence of Diabetes Research in SwedenSwedish Diabetes Association
Available from: 2017-04-28 Created: 2017-04-28 Last updated: 2017-04-28Bibliographically approved
Jansson, L., Barbu, A., Bodin, B., Drott, C. J., Espes, D., Gao, X., . . . Carlsson, P.-O. (2016). Pancreatic islet blood flow and its measurement. Upsala Journal of Medical Sciences, 121(2), 81-95
Open this publication in new window or tab >>Pancreatic islet blood flow and its measurement
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2016 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 2, p. 81-95Article, review/survey (Refereed) Published
Abstract [en]

Pancreatic islets are richly vascularized, and islet blood vessels are uniquely adapted to maintain and support the internal milieu of the islets favoring normal endocrine function. Islet blood flow is normally very high compared with that to the exocrine pancreas and is autonomously regulated through complex interactions between the nervous system, metabolites from insulin secreting beta-cells, endothelium derived mediators, and hormones. The islet blood flow is normally coupled to the needs for insulin release and is usually disturbed during glucose intolerance and overt diabetes. The present review provides a brief background on islet vascular function and especially focuses on available techniques to measure islet blood perfusion. The gold standard for islet blood flow measurements in experimental animals is the microsphere technique, and its advantages and disadvantages will be discussed. In humans there are still no methods to measure islet blood flow selectively, but new developments in radiological techniques hold great hopes for the future.

Keywords
Blood flow measurements, islet blood flow, microspheres, pancreatic islets
National Category
General Practice
Identifiers
urn:nbn:se:uu:diva-299775 (URN)10.3109/03009734.2016.1164769 (DOI)000376695600004 ()27124642 (PubMedID)
Funder
Swedish Research CouncilSwedish Diabetes AssociationSwedish Childhood Cancer FoundationNovo Nordisk
Available from: 2016-07-27 Created: 2016-07-27 Last updated: 2018-01-10Bibliographically approved
Yang, T., Gao, X., Sandberg, M., Zollbrecht, C., Zhang, X.-M., Hezel, M., . . . Carlstrom, M. (2015). Abrogation of adenosine A(1) receptor signalling improves metabolic regulation in mice by modulating oxidative stress and inflammatory responses. Diabetologia, 58(7), 1610-1620
Open this publication in new window or tab >>Abrogation of adenosine A(1) receptor signalling improves metabolic regulation in mice by modulating oxidative stress and inflammatory responses
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2015 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no 7, p. 1610-1620Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis Adenosine is an important regulator of metabolism; however, the role of the A(1) receptor during ageing and obesity is unclear. The aim of this study was to investigate the effects of A(1) signalling in modulating metabolic function during ageing. Methods Age-matched young and aged A (1) (also known as Adora1)-knockout (A (1) (-/-)) and wild-type (A (1) (+/+)) mice were used. Metabolic regulation was evaluated by body composition, and glucose and insulin tolerance tests. Isolated islets and islet arterioles were used to detect islet endocrine and vascular function. Oxidative stress and inflammation status were measured in metabolic organs and systemically. Results Advanced age was associated with both reduced glucose clearance and insulin sensitivity, as well as increased visceral adipose tissue (VAT) in A (1) (+/+) compared with A (1) (-/-) mice. Islet morphology and insulin content were similar between genotypes, but relative changes in in vitro insulin release following glucose stimulation were reduced in aged A (1) (+/+) compared with A (1) (-/-) mice. Islet arteriolar responses to angiotensin II were stronger in aged A (1) (+/+) mice, this being associated with increased NADPH oxidase activity. Ageing resulted in multiple changes in A (1) (+/+) compared with A (1) (-/-) mice, including enhanced NADPH oxidase-derived O-2 (-) formation and NADPH oxidase isoform 2 (Nox2) protein expression in pancreas and VAT; elevated levels of circulating insulin, leptin and proinflammatory cytokines (TNF-alpha, IL-1 beta, IL-6 and IL-12); and accumulation of CD4(+) T cells in VAT. This was associated with impaired insulin signalling in VAT from aged A (1) (+/+) mice. Conclusions/interpretation These studies emphasise that A(1) receptors regulate metabolism and islet endocrine and vascular functions during ageing, including via the modulation of oxidative stress and inflammatory responses, among other things.

Keywords
Insulin sensitivity and resistance, Islets, Metabolic physiology in vivo, Metabolic syndrome, Oxidative stress, Type 2 diabetes, Visceral adipose tissue
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-258321 (URN)10.1007/s00125-015-3570-3 (DOI)000356528900026 ()25835725 (PubMedID)
Funder
Swedish Research Council, 521-2011-2639, 521-2011-3777Swedish Heart Lung Foundation, 20140448, 20110589
Available from: 2015-07-15 Created: 2015-07-13 Last updated: 2017-12-04Bibliographically approved
Zang, G., Sandberg, M., Carlsson, P.-O., Welsh, N., Jansson, L. & Barbu, A. (2015). Activated pancreatic stellate cells can impair pancreatic islet function in mice. Upsala Journal of Medical Sciences, 120(3), 169-180
Open this publication in new window or tab >>Activated pancreatic stellate cells can impair pancreatic islet function in mice
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2015 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 3, p. 169-180Article in journal (Refereed) Published
Abstract [en]

Background. Pancreatic or islet fibrosis is often associated with activated pancreatic stellate cells (PSCs). PSCs are considered not only to promote fibrosis, but also to be associated with glucose intolerance in some diseases. We therefore evaluated morphological and functional relationships between islets and PSCs in the normal mouse pancreas and transplanted islets. Methods. Immunohistochemistry was used to map the presence of PSCs in the normal mouse pancreas and islets implanted under the renal capsule. We isolated and cultured mouse PSCs and characterized them morphologically by immunofluorescence staining. Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets. Results. PSCs were scattered throughout the pancreas, with occasional cells within the islets, particularly in the islet capsule. In islet transplants they were found mainly in the graft periphery. Cultured PSCs became functionally activated and produced several cytokines. Throughout the culture period they linearly increased their production of interleukin-6 and mammalian keratinocyte-derived chemokine. PSC cytokine production was not affected by acute hyperglycemia. Syngeneic islets cocultured with PSCs for 24-48 h increased their insulin release and lowered their insulin content. However, short-term insulin release in batch-type incubations was unaffected after 48 h of co-culture. Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days. Conclusion. Activated PSCs may contribute to impaired islet endocrine function seen in exocrine pancreatitis and in islet fibrosis associated with some cases of type 2 diabetes.

Keywords
Beta-cell replication, insulin release, pancreatic islets, stellate cells
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-261989 (URN)10.3109/03009734.2015.1032453 (DOI)000359819800004 ()25854824 (PubMedID)
Funder
Swedish Research Council, 521-2011-3777
Available from: 2015-09-07 Created: 2015-09-07 Last updated: 2017-12-04Bibliographically approved
Christoffersson, G., Waldén, T., Sandberg, M., Opdenakker, G., Carlsson, P.-O. & Phillipson, M. (2015). Matrix Metalloproteinase-9 Is Essential for Physiological Beta Cell Function and Islet Vascularization in Adult Mice. American Journal of Pathology, 185(4), 1094-1103
Open this publication in new window or tab >>Matrix Metalloproteinase-9 Is Essential for Physiological Beta Cell Function and Islet Vascularization in Adult Mice
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2015 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 185, no 4, p. 1094-1103Article in journal (Refereed) Published
Abstract [en]

The availability of paracrine factors in the islets of Langerhans, and the constitution of the beta cell basement membrane can both be affected by proteolytic enzymes. This study aimed to investigate the effects of the extraceaular matrix-degrading enzyme gelatinase B/matrix metalloproteinase-9 (Mmp-9) on islet function in mice. Islet function of Mmp9-deficient (Mmp9(-/-)) mice and their wild-type Littermates was evaluated both in vivo and in vitro. The pancreata of Mmp9(-/-) mice did not differ from wild type in islet mass or distribution. However, Mmp9(-/-) mice had an impaired response to a glucose toad in vivo, with lower serum insulin levels. The glucose-stimulated insulin secretion was reduced also in vitro in isolated Mmp9(-/-) islets. The vascular density of Mmp9(-/-) islets was lower, and the capillaries had fewer fenestrations, whereas the islet blood flow was threefold higher. These alterations could partly be explained by compensatory changes in the expression of matrix-related proteins. This in-depth investigation of the effects of the loss of MMP9(-/-) function on pancreatic islets uncovers a deteriorated beta cell function that is primarily due to a shift in the beta cell phenotype, but also due to islet vascular aberrations. This likely reflects the importance of a normal islet matrix turnover exerted by MMP-9, and concomitant release of paracrine factors sequestered on the matrix.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-251972 (URN)10.1016/j.ajpath.2014.12.009 (DOI)000351787600019 ()25665793 (PubMedID)
Available from: 2015-05-18 Created: 2015-04-28 Last updated: 2017-12-04Bibliographically approved
Ullsten, S., Grapensparr, L., Sandberg, M. & Carlsson, P.-O. (2015). Schwann cells regulate angiogenesis and blood vessel structure in native and transplanted pancreatic. Paper presented at IPITA/IXA/CTS Joint Congress, NOV 15-19, 2015, Melbourne, AUSTRALIA. Xenotransplantation, 22, S46-S46
Open this publication in new window or tab >>Schwann cells regulate angiogenesis and blood vessel structure in native and transplanted pancreatic
2015 (English)In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, p. S46-S46Article in journal, Meeting abstract (Other academic) Published
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-276047 (URN)000364594100109 ()
Conference
IPITA/IXA/CTS Joint Congress, NOV 15-19, 2015, Melbourne, AUSTRALIA
Available from: 2016-02-09 Created: 2016-02-09 Last updated: 2017-11-30Bibliographically approved
Ullsten, S., Grapensparr, L., Sandberg, M. & Carlsson, P.-O. (2015). Schwann Cells Regulate Angiogenesis And Blood Vessel Structure In Native And Transplanted Pancreatic Islets. Paper presented at Joint Congress of the International-Pancreas-and-Islet-Transplantation-Association, International-Xenotransplantation-Association and Cell-Transplant-Society, NOV 15-19, 2015, Melbourne, AUSTRALIA. Transplantation, 99(11), S75-S75
Open this publication in new window or tab >>Schwann Cells Regulate Angiogenesis And Blood Vessel Structure In Native And Transplanted Pancreatic Islets
2015 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 99, no 11, p. S75-S75Article in journal, Meeting abstract (Other academic) Published
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-281554 (URN)000368625700106 ()
Conference
Joint Congress of the International-Pancreas-and-Islet-Transplantation-Association, International-Xenotransplantation-Association and Cell-Transplant-Society, NOV 15-19, 2015, Melbourne, AUSTRALIA
Available from: 2016-04-05 Created: 2016-03-24 Last updated: 2018-01-10Bibliographically approved
Barbu, A., Jansson, L., Sandberg, M., Quach, M. & Palm, F. (2015). The use of hydrogen gas clearance for blood flow measurements in single endogenous and transplanted pancreatic islets. Microvascular Research, 97, 124-129
Open this publication in new window or tab >>The use of hydrogen gas clearance for blood flow measurements in single endogenous and transplanted pancreatic islets
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2015 (English)In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 97, p. 124-129Article in journal (Refereed) Published
Abstract [en]

The blood perfusion of pancreatic islets is regulated independently from that of the exocrine pancreas, and is of importance for multiple aspects of normal islet function, and probably also during impaired glucose tolerance. Single islet blood flow has been difficult to evaluate due to technical limitations. We therefore adapted a hydrogen gas washout technique using microelectrodes to allow such measurements. Platinum micro-electrodes monitored hydrogen gas clearance from individual endogenous and transplanted islets in the pancreas of male Lewis rats and in human and mouse islets implanted under the renal capsule of male athymic mice. Both in the rat endogenous pancreatic islets as well as in the intra-pancreatically transplanted islets, the vascular conductance and blood flow values displayed a highly heterogeneous distribution, varying by factors 6-10 within the same pancreas. The blood flow of human and mouse islet grafts transplanted in athymic mice was approximately 30% lower than that in the surrounding renal parenchyma. The present technique provides unique opportunities to study the islet vascular dysfunction seen after transplantation, but also allows for investigating the effects of genetic and environmental perturbations on islet blood flow at the single islet level in vivo. (C) 2014 The Authors. Published by Elsevier Inc.

Keywords
Blood flow, Hydrogen gas washout, Pancreatic islets, Transplanted islets, In vivo
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-243450 (URN)10.1016/j.mvr.2014.10.002 (DOI)000346895400018 ()
Note

Andrea Barbu and Leif Jansson contributed equally to this work.

Available from: 2015-02-09 Created: 2015-02-09 Last updated: 2017-12-04Bibliographically approved
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