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Article ; Online: Apolipoprotein CIII Is an Important Piece in the Type-1 Diabetes Jigsaw Puzzle.

Valladolid-Acebes, Ismael / Berggren, Per-Olof / Juntti-Berggren, Lisa

International journal of molecular sciences

2021 Volume 22, Issue 2

Abstract: It is well known that type-2 diabetes mellitus (T2D) is increasing worldwide, but also the autoimmune form, type-1 diabetes (T1D), is affecting more people. The latest estimation from the International Diabetes Federation (IDF) is that 1.1 million ... ...

Abstract	It is well known that type-2 diabetes mellitus (T2D) is increasing worldwide, but also the autoimmune form, type-1 diabetes (T1D), is affecting more people. The latest estimation from the International Diabetes Federation (IDF) is that 1.1 million children and adolescents below 20 years of age have T1D. At present, we have no primary, secondary or tertiary prevention or treatment available, although many efforts testing different strategies have been made. This review is based on the findings that apolipoprotein CIII (apoCIII) is increased in T1D and that in vitro studies revealed that healthy β-cells exposed to apoCIII became apoptotic, together with the observation that humans with higher levels of the apolipoprotein, due to mutations in the gene, are more susceptible to developing T1D. We have summarized what is known about apoCIII in relation to inflammation and autoimmunity in in vitro and in vivo studies of T1D. The aim is to highlight the need for exploring this field as we still are only seeing the top of the iceberg.
MeSH term(s)	Adult ; Apolipoprotein C-III/genetics ; Calcium/metabolism ; Diabetes Mellitus, Type 1/epidemiology ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/pathology ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/pathology ; Gene Expression Regulation/genetics ; Humans ; Inflammation/genetics ; Inflammation/pathology ; Insulin-Secreting Cells/metabolism ; Insulin-Secreting Cells/pathology
Chemical Substances	Apolipoprotein C-III ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-01-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22020932
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Apolipoprotein CIII Reduction Protects White Adipose Tissues against Obesity-Induced Inflammation and Insulin Resistance in Mice.

Recio-López, Patricia / Valladolid-Acebes, Ismael / Berggren, Per-Olof / Juntti-Berggren, Lisa

International journal of molecular sciences

2021 Volume 23, Issue 1

Abstract: Apolipoprotein CIII (apoCIII) is proinflammatory and increases in high-fat diet (HFD)-induced obesity and insulin resistance. We have previously shown that reducing apoCIII improves insulin sensitivity in vivo by complex mechanisms involving liver and ... ...

Abstract	Apolipoprotein CIII (apoCIII) is proinflammatory and increases in high-fat diet (HFD)-induced obesity and insulin resistance. We have previously shown that reducing apoCIII improves insulin sensitivity in vivo by complex mechanisms involving liver and brown adipose tissue. In this study the focus was on subcutaneous (SAT) and visceral (VAT) white adipose tissue (WAT). Mice were either given HFD for 14 weeks and directly from start also treated with antisense oligonucleotide (ASO) against apoCIII or given HFD for 10 weeks and HFD+ASO for an additional 14 weeks. Both groups had animals treated with inactive (Scr) ASO as controls and in parallel chow-fed mice were injected with saline. Preventing an increase or lowering apoCIII in the HFD-fed mice decreased adipocytes' size, reduced expression of inflammatory cytokines and increased expression of genes related to thermogenesis and beiging. Isolated adipocytes from both VAT and SAT from the ASO-treated mice had normal insulin-induced inhibition of lipolysis compared to cells from Scr-treated mice. In conclusion, the HFD-induced metabolic derangements in WATs can be prevented and reversed by lowering apoCIII.
MeSH term(s)	Adipocytes/metabolism ; Adipose Tissue, Brown/metabolism ; Adipose Tissue, White/metabolism ; Animals ; Apolipoprotein C-III/metabolism ; Diet, High-Fat ; Inflammation/metabolism ; Insulin/metabolism ; Insulin Resistance/physiology ; Lipolysis/physiology ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/metabolism ; Thermogenesis/physiology
Chemical Substances	Apolipoprotein C-III ; Insulin
Language	English
Publishing date	2021-12-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23010062
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Book ; Thesis: Elemental content, intracellular pH and cytoplasmic Ca 2+ in insulin secreting cells under physiological conditions and diabetes

Juntti-Berggren, Lisa

(Comprehensive summaries of Uppsala dissertations from the Faculty of Medicine ; 350 ; Acta Universitatis Upsaliensis)

1992

Title variant	insulin-secreting
Author's details	by Lisa Juntti-Berggren
Series title	Comprehensive summaries of Uppsala dissertations from the Faculty of Medicine ; 350 Acta Universitatis Upsaliensis
Collection
Language	English
Size	38 S. : graph. Darst.
Publisher	Almqvist & Wiksell
Publishing place	Stockholm
Publishing country	Sweden
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Uppsala, Univ., Diss., 1992
HBZ-ID	HT007598164
ISBN	91-554-2906-8 ; 978-91-554-2906-5
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Article ; Online: Treatment of the metabolic syndrome by siRNA targeting apolipoprotein CIII.

Recio-López, Patricia / Valladolid-Acebes, Ismael / Hadwiger, Philipp / Hossbach, Markus / Krampert, Monika / Prata, Carla / Berggren, Per-Olof / Juntti-Berggren, Lisa

BioFactors (Oxford, England)

2022 Volume 49, Issue 1, Page(s) 153–172

Abstract: Apolipoprotein CIII (apoCIII) is increased in obesity-induced insulin resistance and type-2 diabetes. Emerging evidences support the advantages of small interfering RNAs (siRNAs) to target disease-causing genes. The aim of this study was to develop ... ...

Abstract	Apolipoprotein CIII (apoCIII) is increased in obesity-induced insulin resistance and type-2 diabetes. Emerging evidences support the advantages of small interfering RNAs (siRNAs) to target disease-causing genes. The aim of this study was to develop siRNAs for in vivo silencing of apoCIII and investigate if this results in metabolic improvements comparable to what we have seen using antisense oligonucelotides against apoCIII. Twenty-four siRNAs were synthesized and tested in a dual luciferase reporter assay. The eight best were selected, based on knockdown at 20 nM, and of these, two were selected based on IC
MeSH term(s)	Mice ; Animals ; Apolipoprotein C-III/genetics ; Apolipoprotein C-III/metabolism ; Apolipoprotein C-III/pharmacology ; Metabolic Syndrome ; RNA, Small Interfering ; Diabetes Mellitus, Type 2 ; Obesity
Chemical Substances	Apolipoprotein C-III ; RNA, Small Interfering
Language	English
Publishing date	2022-08-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	59230-4
ISSN	1872-8081 ; 0951-6433
ISSN (online)	1872-8081
ISSN	0951-6433
DOI	10.1002/biof.1885
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Zs.A 2473: Show issues

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Article: Neither polyphenol-rich red wine nor fenofibrate affects the onset of type-1 diabetes mellitus in the BB rat.

Åvall, Karin / Berggren, Per-Olof / Juntti-Berggren, Lisa

Laboratory animal research

2018 Volume 34, Issue 3, Page(s) 126–131

Abstract: Serum levels of the pro-inflammatory apolipoprotein CIII (apoCIII) are increased in type-1 diabetic (T1D) patients and when β-cells are exposed to apoCIII they undergo apoptosis, which can be prevented by an antibody against apoCIII. We have previously ... ...

Abstract	Serum levels of the pro-inflammatory apolipoprotein CIII (apoCIII) are increased in type-1 diabetic (T1D) patients and when β-cells are exposed to apoCIII they undergo apoptosis, which can be prevented by an antibody against apoCIII. We have previously investigated the BB rat, an animal model that develops a human-like T1D at the age of around 60 days, and found that apoCIII was also increased in sera from pre-diabetic rats and this promoted β-cell death. Lowering apoCIII with an oligonucleotide antisense during a phase of the pre-diabetic period prolonged the time to onset of T1D. In order to find other ways to lower apoCIII we in this study tested non-alcoholic red wine with medium and high concentrations of polyphenols and the lipid-lowering drug, fenofibrate, both reported to decrease the expression of apoCIII by activating peroxisome proliferator-activated receptors. Pre-diabetic BB-rats were treated orally for one month prior to the expected onset of diabetes with the two different wines or fenofibrate. None of the treatments prevented or prolonged the time to onset of diabetes and the expression of apoCIII was unaffected in this animal model for T1D. However, it must be emphasized that this does not exclude that other species can show a response to these substances.
Language	English
Publishing date	2018-09-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2623220-0
ISSN	2233-7660 ; 1738-6055
ISSN (online)	2233-7660
ISSN	1738-6055
DOI	10.5625/lar.2018.34.3.126
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Article ; Online: Apolipoprotein CIII Is an Important Piece in the Type-1 Diabetes Jigsaw Puzzle

Ismael Valladolid-Acebes / Per-Olof Berggren / Lisa Juntti-Berggren

International Journal of Molecular Sciences, Vol 22, Iss 2, p

2021 Volume 932

Abstract	It is well known that type-2 diabetes mellitus (T2D) is increasing worldwide, but also the autoimmune form, type-1 diabetes (T1D), is affecting more people. The latest estimation from the International Diabetes Federation (IDF) is that 1.1 million children and adolescents below 20 years of age have T1D. At present, we have no primary, secondary or tertiary prevention or treatment available, although many efforts testing different strategies have been made. This review is based on the findings that apolipoprotein CIII (apoCIII) is increased in T1D and that in vitro studies revealed that healthy β-cells exposed to apoCIII became apoptotic, together with the observation that humans with higher levels of the apolipoprotein, due to mutations in the gene, are more susceptible to developing T1D. We have summarized what is known about apoCIII in relation to inflammation and autoimmunity in in vitro and in vivo studies of T1D. The aim is to highlight the need for exploring this field as we still are only seeing the top of the iceberg.
Keywords	apolipoprotein CIII ; type-1 diabetes ; β-cells ; apoptosis ; inflammation ; calcium channels ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Apolipoprotein CIII Reduction Protects White Adipose Tissues against Obesity-Induced Inflammation and Insulin Resistance in Mice

Patricia Recio-López / Ismael Valladolid-Acebes / Per-Olof Berggren / Lisa Juntti-Berggren

International Journal of Molecular Sciences, Vol 23, Iss 62, p

2022 Volume 62

Abstract	Apolipoprotein CIII (apoCIII) is proinflammatory and increases in high-fat diet (HFD)-induced obesity and insulin resistance. We have previously shown that reducing apoCIII improves insulin sensitivity in vivo by complex mechanisms involving liver and brown adipose tissue. In this study the focus was on subcutaneous (SAT) and visceral (VAT) white adipose tissue (WAT). Mice were either given HFD for 14 weeks and directly from start also treated with antisense oligonucleotide (ASO) against apoCIII or given HFD for 10 weeks and HFD+ASO for an additional 14 weeks. Both groups had animals treated with inactive (Scr) ASO as controls and in parallel chow-fed mice were injected with saline. Preventing an increase or lowering apoCIII in the HFD-fed mice decreased adipocytes’ size, reduced expression of inflammatory cytokines and increased expression of genes related to thermogenesis and beiging. Isolated adipocytes from both VAT and SAT from the ASO-treated mice had normal insulin-induced inhibition of lipolysis compared to cells from Scr-treated mice. In conclusion, the HFD-induced metabolic derangements in WATs can be prevented and reversed by lowering apoCIII.
Keywords	apolipoprotein CIII ; diet-induced obesity ; insulin resistance ; white adipose tissue ; inflammation ; antisense oligonucleotides ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effectiveness of Antivirals in a Type 1 Diabetes Model and the Move Toward Human Trials.

Niklasson, Bo / Klitz, William / Juntti-Berggren, Lisa / Berggren, Per-Olof / Lindquist, Lars

Viral immunology

2020 Volume 33, Issue 9, Page(s) 594–599

Abstract: A Picornavirus (Ljungan virus [LV]) originally found in bank voles has been associated with type 1 diabetes (T1D) in its wild rodent reservoir, but also associated with T1D in a laboratory rat model for the disease, the diabetes prone (DP) Bio Breeding ( ... ...

Abstract	A Picornavirus (Ljungan virus [LV]) originally found in bank voles has been associated with type 1 diabetes (T1D) in its wild rodent reservoir, but also associated with T1D in a laboratory rat model for the disease, the diabetes prone (DP) Bio Breeding (BB) rat. Successful treatment of diabetes in this rat model, using experimental antiviral compounds directed against picornavirus, has been reported. In the present study we show significant clinical response in DP-BB rats using antiviral compounds available for human use (Pleconaril, Efavirenz, and Ribavirin). Presence of LV picornavirus antigen has been detected in islets of Langerhans from both human and the T1D rat model with clear morphological similarity. Based on these data it would be of interest to test antiviral treatment in patients with newly diagnosed T1D. Successful outcome will offer both proof of concept regarding the role of virus involvement in the disease and possibly a first generation treatment interrupting a persistent infection and stopping
MeSH term(s)	Adult ; Alkynes/therapeutic use ; Animals ; Antiviral Agents/therapeutic use ; Benzoxazines/therapeutic use ; Cyclopropanes/therapeutic use ; Diabetes Mellitus, Type 1/drug therapy ; Humans ; Male ; Oxadiazoles/therapeutic use ; Oxazoles/therapeutic use ; Proof of Concept Study ; Rats ; Ribavirin/therapeutic use
Chemical Substances	Alkynes ; Antiviral Agents ; Benzoxazines ; Cyclopropanes ; Oxadiazoles ; Oxazoles ; Ribavirin (49717AWG6K) ; pleconaril (9H4570Q89D) ; efavirenz (JE6H2O27P8)
Language	English
Publishing date	2020-08-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639075-4
ISSN	1557-8976 ; 0882-8245
ISSN (online)	1557-8976
ISSN	0882-8245
DOI	10.1089/vim.2020.0039
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 2227: Show issues

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Article ; Online: Non-functioning neuroendocrine pancreatic tumors transforming to malignant insulinomas - four cases and review of the literature.

Juhlin, C Christofer / Skoglund, Sissela / Juntti-Berggren, Lisa / Karlberg, Mia / Calissendorff, Jan

Neuro endocrinology letters

2020 Volume 40, Issue 4, Page(s) 175–183

Abstract: Objective: Neuroendocrine tumors of the pancreas (Pan-NETs) are rare, but among the most common neuroendocrine neoplasias. They are mostly slowly growing with a capacity to metastasize, but transition to a higher grade occurs, which lead to a more ... ...

Abstract	Objective: Neuroendocrine tumors of the pancreas (Pan-NETs) are rare, but among the most common neuroendocrine neoplasias. They are mostly slowly growing with a capacity to metastasize, but transition to a higher grade occurs, which lead to a more aggressive tumor phenotype. Very seldom, non-functional tumors can become hormonally active. Here we present four patients with originally non-functional Pan-NETs that subsequently started to produce insulin or its precursors, causing severe hypoglycemia. Methods: We reviewed the medical files, biochemistry and radiological investigations. Pathology tissue samples were re-examined, and additional immunohistochemical analyses were performed. Results: Four patients; three women and one man, aged 51, 61, 65 and 68 years at diagnosis developed malignant insulinomas 2, 5, 6 and 7 years respectively after initial diagnosis of non-secreting Pan-NETs. They had all metastatic disease at diagnosis. Ki-67 was initially 2, 5 and 6% and progressed to 25, 17 and 45%, respectively. In one patient the initial Ki-67 was 5% but was not reexamined. All four patients died due to their cancer disease within 12, 6, 19 and 29 months after treatment for hypoglycemia commenced. The clinical profile and/or review of the histopathology confirmed all original lesions as non-functional Pan-NETs with subsequent transformation into insulin-producing tumors. Conclusions: Non-functional, metastatic Pan-NETs may transform to insulin secreting lesions, with negative impact on prognosis. Therefore, if symptoms as hypoglycemia develops continuous follow-up of clinical parameters, biochemical profiles of pancreatic hormones and histopathological evaluation of proliferation is suggested to detect changes in characteristics of these malignant neoplasms.
MeSH term(s)	Aged ; Cell Transformation, Neoplastic/pathology ; Female ; Humans ; Insulinoma/pathology ; Male ; Middle Aged ; Neuroendocrine Tumors/pathology ; Pancreatic Neoplasms/pathology ; Prognosis
Language	English
Publishing date	2020-02-21
Publishing country	Sweden
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	135951-4
ISSN	2354-4716 ; 0172-780X
ISSN (online)	2354-4716
ISSN	0172-780X
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Article ; Online: Apolipoprotein CIII is a new player in diabetes.

Juntti-Berggren, Lisa / Berggren, Per-Olof

Current opinion in lipidology

2016 Volume 28, Issue 1, Page(s) 27–31

Abstract: Purpose of review: Type-1 and type-2 diabetes are diseases with an increasing number of patients and a complex, multifactorial pathogenesis. Apolipoprotein (apo) CIII is increased in both types of diabetes and interventions preventing the increase have ... ...

Abstract	Purpose of review: Type-1 and type-2 diabetes are diseases with an increasing number of patients and a complex, multifactorial pathogenesis. Apolipoprotein (apo) CIII is increased in both types of diabetes and interventions preventing the increase have effects on the development of diabetes. Recent findings: ApoCIII affects intracellular Ca-handling by activating voltage-gated Ca-channels. ApoCIII is produced within the pancreatic islets and it increases in parallel with the development of insulin resistance and type-2 diabetes. Preventing the increase maintains a normal glucose tolerance as well as Ca-handling and no signs of inflammation can be seen in islets wherein the augmented local production of the apolipoprotein is absent. Summary: ApoCIII has been found to interfere with both function and survival of the β-cell and thereby promote the development of diabetes. Increased levels of this apolipoprotein affects intracellular Ca-handling and insulin sensitivity, which finally results in impaired glucose homeostasis and diabetes. Interestingly, in a type-1 diabetes rat model lowering of apoCIII delays onset of diabetes. In type-2 diabetes insulin resistance within the pancreatic islets leads to a local increase in apoCIII that promotes inflammation and β-cell dysfunction. Hence, targeting apoCIII may constitute a novel pharmacological strategy to treat both type-1 and type-2 diabetes.
MeSH term(s)	Animals ; Apolipoprotein C-III/metabolism ; Diabetes Mellitus/metabolism ; Humans
Chemical Substances	Apolipoprotein C-III
Language	English
Publishing date	2016-11-22
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1045394-5
ISSN	1473-6535 ; 0957-9672
ISSN (online)	1473-6535
ISSN	0957-9672
DOI	10.1097/MOL.0000000000000372
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