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Nord, Christoffer
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Publications (10 of 16) Show all publications
Grong, E., Nord, C., Arbo, I. B., Eriksson, M., Kulseng, B. E., Ahlgren, U. & Mårvik, R. (2018). The effect of hypergastrinemia following sleeve gastrectomy and pantoprazole on type 2 diabetes mellitus and beta-cell mass in Goto-Kakizaki rats. Journal of Endocrinological Investigation, 41(6), 691-701
Open this publication in new window or tab >>The effect of hypergastrinemia following sleeve gastrectomy and pantoprazole on type 2 diabetes mellitus and beta-cell mass in Goto-Kakizaki rats
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2018 (English)In: Journal of Endocrinological Investigation, ISSN 0391-4097, E-ISSN 1720-8386, Vol. 41, no 6, p. 691-701Article in journal (Refereed) Published
Abstract [en]

Purpose: Metabolic surgery alters the secretion of gastrointestinal hormones that influence glycemic control. Elevated gastrin has been suggested to benefit patients with type 2 diabetes and has been reported following sleeve gastrectomy in rats. The present study compares the effect of hypergastrinemia following sleeve gastrectomy with proton-pump inhibitor therapy on glycemic control and beta-cell mass in lean, diabetic animals.

Methods: Thirty-three diabetic Goto-Kakizaki rats were randomized into pantoprazole + sham operation (GK-PPI), sleeve gastrectomy (GK-SG) and vehicle + sham operation (GK-V). Body weight, glucose parameters, HbA1c, glucagon-like peptide 1, gastrin, insulin and lipids were evaluated for eighteen postoperative weeks. Total beta-cell mass was quantified by optical projection tomography.

Results: After surgery, body weight development was equal among groups (Pg = 0.75). Fasting and stimulated gastrin increased for GK-PPI and GK-SG vs. GK-V (p < 0.05 for all). Fasting blood glucose was decreased for GK-PPI and GK-SG vs. GK-V (p < 0.05 and p = 0.052). HbA1c was lower for GK-SG vs. GK-V at 6 weeks and for GK-PPI vs. GK-V at twelve- and eighteen weeks postoperative (p < 0.05 for all); a borderline difference was observed for GK-SG vs. GK-V at 18 weeks (p = 0.054). Total- and LDL cholesterol was elevated for GK-PPI compared to the other two groups (p < 0.05 for all). Beta-cell mass did not differ among groups (p = 0.35).

Conclusions: Hypergastrinemia following sleeve gastrectomy and pantoprazole has a similar, modest effect on glycemic control in Goto-Kakizaki rats but does not enhance beta-cell mass after 18 weeks. Hypergastrinemia in the setting of T2DM might be of clinical relevance.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
sleeve gastrectomy, pantoprazole, gastrin, optical projection tomography, beta-cell mass, glycosylated hemoglobin
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-148827 (URN)10.1007/s40618-017-0793-9 (DOI)000432236400008 ()29168078 (PubMedID)2-s2.0-85034636636 (Scopus ID)
Available from: 2018-06-13 Created: 2018-06-13 Last updated: 2018-06-13Bibliographically approved
Nord, C., Eriksson, M., Dicker, A., Eriksson, A., Grong, E., Ilegems, E., . . . Ahlgren, U. (2017). Biochemical profiling of diabetes disease progression by multivariate vibrational microspectroscopy of the pancreas. Scientific Reports, 7, Article ID 6646.
Open this publication in new window or tab >>Biochemical profiling of diabetes disease progression by multivariate vibrational microspectroscopy of the pancreas
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 6646Article in journal (Refereed) Published
Abstract [en]

Despite the dramatic increase in the prevalence of diabetes, techniques for in situ studies of the underlying pancreatic biochemistry are lacking. Such methods would facilitate obtaining mechanistic understanding of diabetes pathophysiology and aid in prognostic and/or diagnostic assessments. In this report we demonstrate how a multivariate imaging approach (orthogonal projections to latent structures - discriminant analysis) can be applied to generate full vibrational microspectroscopic profiles of pancreatic tissues. These profiles enable extraction of known and previously unrecorded biochemical alterations in models of diabetes, and allow for classification of the investigated tissue with regards to tissue type, strain and stage of disease progression. Most significantly, the approach provided evidence for dramatic alterations of the pancreatic biochemistry at the initial onset of immune-infiltration in the Non Obese Diabetic model for type 1 diabetes. Further, it enabled detection of a previously undocumented accumulation of collagen fibrils in the leptin deficient ob/ob mouse islets. By generating high quality spectral profiles through the tissue capsule of hydrated human pancreata and by in vivo Raman imaging of pancreatic islets transplanted to the anterior chamber of the eye, we provide critical feasibility studies for the translation of this technique to diagnostic assessments of pancreatic biochemistry in vivo.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-138420 (URN)10.1038/s41598-017-07015-z (DOI)000406366000004 ()
Available from: 2017-08-23 Created: 2017-08-23 Last updated: 2018-06-09Bibliographically approved
Parween, S., Eriksson, M., Nord, C., Kostromina, E. & Ahlgren, U. (2017). Spatial and quantitative datasets of the pancreatic beta-cell mass distribution in lean and obese mice. Scientific Data, 4, Article ID 170031.
Open this publication in new window or tab >>Spatial and quantitative datasets of the pancreatic beta-cell mass distribution in lean and obese mice
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2017 (English)In: Scientific Data, E-ISSN 2052-4463, Vol. 4, article id 170031Article in journal (Refereed) Published
Abstract [en]

A detailed understanding of pancreatic β-cell mass distribution is a key element to fully appreciate the pathophysiology of models of diabetes and metabolic stress. Commonly, such assessments have been performed by stereological approaches that rely on the extrapolation of two-dimensional data and provide very limited topological information. We present ex vivo optical tomographic data sets of the full β-cell mass distribution in cohorts of obese ob/ob mice and their lean controls, together with information about individual islet β-cell volumes, their three-dimensional coordinates and shape throughout the volume of the pancreas between 4 and 52 weeks of age. These data sets offer the currently most comprehensive public record of the β-cell mass distribution in the mouse. As such, they may serve as a quantitative and topological reference for the planning of a variety of in vivo or ex vivo experiments including computational modelling and statistical analyses. By shedding light on intra- and inter-lobular variations in β-cell mass distribution, they further provide a powerful tool for the planning of stereological sampling assessments.

National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:umu:diva-133764 (URN)10.1038/sdata.2017.31 (DOI)000396109500001 ()
Available from: 2017-05-03 Created: 2017-05-03 Last updated: 2018-06-09Bibliographically approved
Parween, S., Kostromina, E., Nord, C., Eriksson, M., Lindström, P. & Ahlgren, U. (2016). Intra-islet lesions and lobular variations in β-cell mass expansion in ob/ob mice revealed by 3D imaging of intact pancreas. Scientific Reports, 6, Article ID 34885.
Open this publication in new window or tab >>Intra-islet lesions and lobular variations in β-cell mass expansion in ob/ob mice revealed by 3D imaging of intact pancreas
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 34885Article in journal (Refereed) Published
Abstract [en]

The leptin deficient ob/ob mouse is a widely used model for studies on initial aspects of metabolic disturbances leading to type 2 diabetes, including insulin resistance and obesity. Although it is generally accepted that ob/ob mice display a dramatic increase in β-cell mass to compensate for increased insulin demand, the spatial and quantitative dynamics of β-cell mass distribution in this model has not been assessed by modern optical 3D imaging techniques. We applied optical projection tomography and ultramicroscopy imaging to extract information about individual islet β-cell volumes throughout the volume of ob/ob pancreas between 4 and 52 weeks of age. Our data show that cystic lesions constitute a significant volume of the hyperplastic ob/ob islets. We propose that these lesions are formed by a mechanism involving extravasation of red blood cells/plasma due to increased islet vessel blood flow and vessel instability. Further, our data indicate that the primary lobular compartments of the ob/ob pancreas have different potentials for expanding their β-cell population. Unawareness of the characteristics of β-cell expansion in ob/ob mice presented in this report may significantly influence ex vivo and in vivo assessments of this model in studies of β-cell adaptation and function.

Place, publisher, year, edition, pages
Nature Publishing Group, 2016
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-127539 (URN)10.1038/srep34885 (DOI)000392007800001 ()27713548 (PubMedID)2-s2.0-84990210699 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme, 289932Swedish Research Council
Available from: 2016-11-15 Created: 2016-11-15 Last updated: 2018-06-09Bibliographically approved
Grong, E., Kulseng, B., Arbo, I. B., Nord, C., Eriksson, M., Ahlgren, U. & Mårvik, R. (2016). Sleeve gastrectomy, but not duodenojejunostomy, preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography. Surgical Endoscopy, 30(2), 532-542
Open this publication in new window or tab >>Sleeve gastrectomy, but not duodenojejunostomy, preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography
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2016 (English)In: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 30, no 2, p. 532-542Article in journal (Refereed) Published
Abstract [en]

Background In type 2 diabetes mellitus, there is a progressive loss of beta-cell mass. Bariatric surgery has in recent investigations showed promising results in terms of diabetes remission, but little is established regarding the effect of surgery on the survival or regeneration of pancreatic beta-cells. In this study, we aim to explore how bariatric surgery with its subsequent hormonal alterations affects the islets of Langerhans.

Methods Twenty-four Goto-Kakizaki rats were operated with duodenojejunostomy (DJ), sleeve gastrectomy (SG) or sham operation. From the 38th week after surgery, body weight, fasting blood glucose, glycosylated hemoglobin, mixed meal tolerance with repeated measures of insulin, glucagon-like peptide 1, gastrin and total ghrelin were evaluated. Forty-six weeks after surgery, the animals were euthanized and the total beta-cell mass in all animals was examined by three-dimensional volume quantification by optical projection tomography based on the signal from insulin-specific antibody staining.

Results Body weight did not differ between groups (Pg = 0.37). SG showed lower fasting blood glucose compared to DJ and sham (Pg = 0.037); HbA1c levels in SG were lower compared to DJ only (p\0.05). GLP-1 levels were elevated for DJ compared to SG and sham (Pg = 0.001), whereas gastrin levels were higher in SG compared to the two other groups (Pg = 0.002). Beta-cell mass was significantly greater in animals operated with SG compared to both DJ and sham (p = 0.036).

Conclusion Sleeve gastrectomy is superior to duodenojejunostomy and sham operation when comparing the preservation of beta-cell mass 46 weeks after surgery in Goto-Kakizaki rats. This could be related to both the increased gastrin levels and the long-term improvement in glycemic parameters observed after this procedure.

Keywords
Duodenojejunostomy, Sleeve gastrectomy, Gastrin, Glucagon-like peptide 1, Beta-cell mass, Optical projection tomography, Goto-Kakizaki rats, Type 2 diabetes mellitus
National Category
Cell and Molecular Biology Endocrinology and Diabetes Surgery
Identifiers
urn:nbn:se:umu:diva-117395 (URN)10.1007/s00464-015-4236-4 (DOI)000369335900018 ()26065537 (PubMedID)
Available from: 2016-03-30 Created: 2016-02-29 Last updated: 2018-06-07Bibliographically approved
Nord, C. (2016). The Colours of Diabetes: advances and novel applications of molecular optical techniques for studies of the pancreas. (Doctoral dissertation). Umeå: Umeå universitet
Open this publication in new window or tab >>The Colours of Diabetes: advances and novel applications of molecular optical techniques for studies of the pancreas
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Diabetes is a rapidly increasing health problem. In a global perspective,approximately 415 million people suffered from diabetes in 2015 and this number ispredicted to increase to 640 million by 2040. To tackle this pandemic there is a needfor better analytical tools by which we can increase our understanding of the disease.One discipline that has already provided much needed insight to diabetes etiology isoptical molecular imaging. Using various forms of light it is possible to create animage of the analysed sample that can provide information about molecularmechanistic aspects of the disease and to follow spatial and temporal dynamics.

The overall aim of this thesis is to improve and adapt existing andnovel optical imaging approaches for their specific use in diabetes research. Hereby,we have focused on three techniques: (I) Optical projection tomography (OPT),which can be described as the optical equivalent of x-ray computed tomography(CT), and two vibrational microspectroscopic (VMS) techniques, which records theunique vibrational signatures of molecules building up the sample: (II) Fouriertransforminfrared vibrational microspectroscopy (FT-IR) and (III) Ramanvibrational microspectroscopy (Raman).

The computational tools and hardware applications presented here generallyimprove OPT data quality, processing speed, sample size and channel capacity.Jointly, these developments enable OPT as a routine tool in diabetes research,facilitating aspects of e.g. pancreatic β-cell generation, proliferation,reprogramming, destruction and preservation to be studied throughout the pancreaticvolume and in large cohorts of experimental animals. Further, a novel application ofmultivariate analysis of VMS data derived from pancreatic tissues is introduced.This approach enables detection of novel biochemical alterations in the pancreasduring diabetes disease progression and can be used to confirm previously reportedbiochemical alterations, but at an earlier stage. Finally, our studies indicate thatRaman imaging is applicable to in vivo studies of grafted islets of Langerhans,allowing for longitudinal studies of pancreatic islet biochemistry.viIn summary, presented here are new and improved methods by which opticalimaging techniques can be utilised to study 3D-spatial, quantitative andmolecular/biochemical alterations of the normal and diseased pancreas.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2016. p. 55
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1811
Keywords
Optical projection tomography, Technique development, Near-infrared, 3D visualization, Biomedical imaging, ß-cell mass, Diabetes, Vibrational micro spectroscopy
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-119845 (URN)978-91-7601-426-4 (ISBN)
Public defence
2016-05-26, Hörsal Betula, Målpunkt L, Plan 0, Norrlands Universitets sjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2016-05-04 Created: 2016-04-29 Last updated: 2018-06-07Bibliographically approved
Jones, I., Hägglund, A.-C., Törnqvist, G., Nord, C., Ahlgren, U. & Carlsson, L. (2015). A novel mouse model of tuberous sclerosis complex (TSC): eye-specific Tsc1-ablation disrupts visual-pathway development. Disease Models and Mechanisms, 8(12), 1517-1529
Open this publication in new window or tab >>A novel mouse model of tuberous sclerosis complex (TSC): eye-specific Tsc1-ablation disrupts visual-pathway development
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2015 (English)In: Disease Models and Mechanisms, ISSN 1754-8403, E-ISSN 1754-8411, Vol. 8, no 12, p. 1517-1529Article in journal (Refereed) Published
Abstract [en]

Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome that is best characterised by neurodevelopmental deficits and the presence of benign tumours (called hamartomas) in affected organs. This multi-organ disorder results from inactivating point mutations in either the TSC1 or the TSC2 genes and consequent activation of the canonical mammalian target of rapamycin complex 1 signalling (mTORC1) pathway. Because lesions to the eye are central to TSC diagnosis, we report here the generation and characterisation of the first eye-specific TSC mouse model. We demonstrate that conditional ablation of Tsc1 in eye-committed progenitor cells leads to the accelerated differentiation and subsequent ectopic radial migration of retinal ganglion cells. This results in an increase in retinal ganglion cell apoptosis and consequent regionalised axonal loss within the optic nerve and topographical changes to the contra- and ipsilateral input within the dorsal lateral geniculate nucleus. Eyes from adult mice exhibit aberrant retinal architecture and display all the classic neuropathological hallmarks of TSC, including an increase in organ and cell size, ring heterotopias, hamartomas with retinal detachment, and lamination defects. Our results provide the first major insight into the molecular etiology of TSC within the developing eye and demonstrate a pivotal role for Tsc1 in regulating various aspects of visual-pathway development. Our novel mouse model therefore provides a valuable resource for future studies concerning the molecular mechanisms underlying TSC and also as a platform to evaluate new therapeutic approaches for the treatment of this multi-organ disorder.

National Category
Other Basic Medicine
Identifiers
urn:nbn:se:umu:diva-120197 (URN)10.1242/dmm.021972 (DOI)000368905300004 ()26449264 (PubMedID)
Available from: 2016-05-11 Created: 2016-05-11 Last updated: 2018-06-07Bibliographically approved
Witek, B., El Wakil, A., Nord, C., Ahlgren, U., Eriksson, M., Vernersson-Lindahl, E., . . . Palmer, R. H. (2015). Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism. PLoS ONE, 10(5), Article ID e0123542.
Open this publication in new window or tab >>Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0123542Article in journal (Refereed) Published
Abstract [en]

Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-106607 (URN)10.1371/journal.pone.0123542 (DOI)000356768100016 ()25955180 (PubMedID)
Available from: 2015-07-28 Created: 2015-07-24 Last updated: 2018-06-07Bibliographically approved
Hörnblad, A., Nord, C., Parween, S., Ahnfelt-Rønne, J. & Ahlgren, U. (2015). The pancreas (1ed.). In: Richard Baldock, Jonathan Bard, Duncan R. Davidson and Gillian Morriss-Kay (Ed.), Kaufman's atlas of mouse development supplement: with coronal sections (pp. 85-94). Elsevier
Open this publication in new window or tab >>The pancreas
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2015 (English)In: Kaufman's atlas of mouse development supplement: with coronal sections / [ed] Richard Baldock, Jonathan Bard, Duncan R. Davidson and Gillian Morriss-Kay, Elsevier, 2015, 1, p. 85-94Chapter in book (Refereed)
Abstract [en]

This chapter aims to provide a three-dimensional description of the key morphological events, through which a discrete region of the early gut epithelium, as well as its associated mesenchyme, gives rise to the adult pancreas. Facilitated by recent advances in optical imaging techniques, including light sheet fluorescence microscopy and optical projection tomography, we present image series illustrating the growth of the organ and the formation of key morphological and anatomical features. Given the close developmental relationship between the pancreas-associated mesenchyme and the spleen anlage, and thus the potential for the developing spleen to influence pancreas morphogenesis, we include a brief section which covers the early development of this organ. Finally, we describe the spatial and quantitative distribution of the pancreatic endocrine (β-cell) component in adult mice and highlight lobular heterogeneities that may affect phenotypical evaluations of the gland.

Place, publisher, year, edition, pages
Elsevier, 2015 Edition: 1
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-134657 (URN)978-0-12-800043-4 (ISBN)978-0-12-800913-0 (ISBN)
Available from: 2017-06-01 Created: 2017-06-01 Last updated: 2018-06-09Bibliographically approved
Nord, H., Burguiere, A.-C., Muck, J., Nord, C., Ahlgren, U. & von Hofsten, J. (2014). Differential regulation of myosin heavy chains defines new muscle domains in zebrafish. Molecular Biology of the Cell, 25(8), 1384-1395
Open this publication in new window or tab >>Differential regulation of myosin heavy chains defines new muscle domains in zebrafish
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2014 (English)In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 25, no 8, p. 1384-1395Article in journal (Refereed) Published
Abstract [en]

Numerous muscle lineages are formed during myogenesis within both slow-and fast-specific cell groups. In this study, we show that six fast muscle-specific myosin heavy chain genes have unique expression patterns in the zebrafish embryo. The expression of tail-specific myosin heavy chain (fmyhc2.1) requires wnt signaling and is essential for fast muscle organization within the tail. Retinoic acid treatment results in reduced wnt signaling, which leads to loss of the fmyhc2.1 domain. Retinoic acid treatment also results in a shift of muscle identity within two trunk domains defined by expression of fmyhc1.2 and fmyhc1.3 in favor of the anteriormost myosin isoform, fmyhc1.2. In summary, we identify new muscle domains along the anteroposterior axis in the zebrafish that are defined by individual nonoverlapping, differentially regulated expression of myosin heavy chain isoforms.

Place, publisher, year, edition, pages
American Society for Cell Biology, 2014
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-92681 (URN)10.1091/mbc.E13-08-0486 (DOI)000339649400017 ()24523292 (PubMedID)
Available from: 2014-09-01 Created: 2014-09-01 Last updated: 2018-06-07Bibliographically approved
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