Asymmetrical distribution of δ and PP cells in human pancreatic islets

The aim of this study was to evaluate the location of PP and δ cells in relation to the vascularization within human pancreatic islets. To this end, pancreas sections were analysed by immunofluorescence using antibodies against endocrine islet and endothelial cells. Staining in different islet areas corresponding to islet cells adjacent or not to peripheral or central vascular channels was quantified by computerized morphometry. As results, α, PP and δ cells were preferentially found adjacent to vessels. In contrast to α cells, which were evenly distributed between islet periphery and intraislet vascular channels, PP and δ cells had asymmetric and opposite distributions: PP staining was higher and somatostatin staining was lower in the islet periphery than in the area around intraislet vascular channels. Additionally, frequencies of PP and δ cells were negatively correlated in the islets. No difference was observed between islets from the head and the tail of the pancreas, and from type 2 diabetic and non-diabetic donors. In conclusion, the distribution of δ cells differs from that of PP cells in human islets, suggesting that vessels at the periphery and at the centre of islets drain different hormonal cocktails.

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GABAA receptor-mediated currents and hormone mRNAs in cells expressing more than one hormone transcript in intact human pancreatic islets

10.1101/635144 ◽

2019 ◽

Author(s):

Sergiy V. Korol ◽

Zhe Jin ◽

Bryndis Birnir

Keyword(s):

Pancreatic Islets ◽

Single Channel ◽

Islet Cells ◽

Cell Types ◽

Cell Type ◽

Expression Ratio ◽

Human Pancreatic Islets ◽

The Difference ◽

Type 2 Diabetic

AbstractIn pancreatic islets the major cell-types are α, β and δ cells, secreting the hormones glucagon (GCG), insulin (INS) and somatostatin (SST), respectively. The GABA (γ-aminobutyric acid) signalling system is expressed in human pancreatic islets. We have previously used single-cell RT-PCR in combination with current recordings to correlate expression of single hormone transcript with functional GABAA receptor (iGABAAR) properties in islets. Here we extended these studies to islet cells from non-diabetic and type 2 diabetic donors that express mRNAs for more than one hormone. We detected cells expressing double (α/β, α/δ, β/δ cell-types) and triple (α/β/δ cell-type) hormone transcripts. The most common mixed-identity cell-type was the α/β group where the cells could be grouped into β- and α-like subgroups. The β-like cells had low GCG/INS expression ratio (< 0.6) and significantly higher frequency of single-channel iGABAAR openings than the α-like cells where the GCG/INS expression ratio was high (> 1.2). The difference in expression levels and single channel iGABAAR characteristics varied in the α/β/δ cell-type. No correlation was observed between the cell-types identity with time in culture or cell size. Clearly, multiple hormone transcripts can be expressed in islet cells whereas iGABAAR functional properties appear α or β cell specific.

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Expression Profile of SARS-CoV-2 Host Receptors in Human Pancreatic Islets Revealed Upregulation of ACE2 in Diabetic Donors

Biology ◽

10.3390/biology9080215 ◽

2020 ◽

Vol 9 (8) ◽

pp. 215 ◽

Cited By ~ 5

Author(s):

Jalal Taneera ◽

Waseem El-Huneidi ◽

Mawieh Hamad ◽

Abdul Khader Mohammed ◽

Esraa Elaraby ◽

...

Keyword(s):

Pancreatic Islets ◽

Endocrine Cells ◽

Human Islets ◽

Diabetic Patients ◽

Rna Seq ◽

Human Pancreatic Islets ◽

Diabetes Status ◽

Subcutaneous Adipose ◽

Type 2 Diabetic

Cellular entry of SARS-CoV-2 is thought to occur through the binding of viral spike S1 protein to ACE2. The entry process involves priming of the S protein by TMPRSS2 and ADAM17, which collectively mediate the binding and promote ACE2 shedding. In this study, microarray and RNA-sequencing (RNA-seq) expression data were utilized to profile the expression pattern of ACE2, ADAM17, and TMPRSS2 in type 2 diabetic (T2D) and non-diabetic human pancreatic islets. Our data show that pancreatic islets express all three receptors irrespective of diabetes status. The expression of ACE2 was significantly increased in diabetic/hyperglycemic islets compared to non-diabetic/normoglycemic. Islets from female donors showed higher ACE2 expression compared to males; the expression of ADAM17 and TMPRSS2 was not affected by gender. The expression of the three receptors was statistically similar in young (≤40 years old) versus old (≥60 years old) donors. Obese (BMI > 30) donors have significantly higher expression levels of ADAM17 and TMPRSS2 relative to those from non-obese donors (BMI < 25). TMPRSS2 expression correlated positively with HbA1c and negatively with age, while ADAM17 and TMPRSS2 correlated positively with BMI. The expression of the three receptors was statistically similar in muscle and subcutaneous adipose tissues obtained from diabetic and nondiabetic donors. Lastly, ACE2 expression was higher in sorted pancreatic β-cell relative to other endocrine cells. In conclusion, ACE2 expression is increased in diabetic human islets. More studies are required to investigate whether variations of ACE2 expression could explain the severity of COVID-19 infection-related symptoms between diabetics and non-diabetic patients.

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Expression Pattern of 12-Lipoxygenase in Human Islets With Type 1 Diabetes and Type 2 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-3630 ◽

2015 ◽

Vol 100 (3) ◽

pp. E387-E395 ◽

Cited By ~ 26

Author(s):

Wojciech J. Grzesik ◽

Joseph L. Nadler ◽

Yui Machida ◽

Jerry L. Nadler ◽

Yumi Imai ◽

...

Keyword(s):

Outcome Measure ◽

Islet Cells ◽

Human Islets ◽

Β Cells ◽

Β Cell ◽

Diabetes Development ◽

12 Lipoxygenase ◽

Type 2 Diabetic

Context: Inflammation in the pancreas can cause β-cell stress, leading to diabetes development. Access to human pancreas tissues via the Network for Pancreatic Organ Donors with Diabetes (nPOD) has allowed characterization of pathways leading to this inflammation. Objective: 12-Lipoxygenase (12-LO) induces inflammation and has been implicated in diabetes development. Our goal was to determine expression of 12-LO in human islets from control, autoantibody-positive, type 1 diabetic, and type 2 diabetic nPOD pancreas donors. Design: Pancreas tissues from nPOD donors were examined by immunohistochemistry and immunofluorescence for islet expression of 12-LO in different subsets of islet cells. Participants: Donor pancreas samples were obtained from nPOD based on disease status (control, n = 7; autoantibody-positive, n = 8; type 1 diabetic, n = 17; or type 2 diabetic donors, n = 15). Main Outcome Measure: Determination of 12-LO expression within human islets served as the main outcome measure, including distinguishing which types of islet cells expressed 12-LO. Results: Islets from control participants (nondiabetic) lacked islet expression of 12-LO. Of donors in the other groups, 25% to 37% expressed islet 12-LO with a clear inverse relation between the numbers of β-cells and 12-LO+ cells within islets of 12-LO+ cases. 12-LO expression was not seen within macrophages, endothelial cells, α-cells, or β-cells, but only within cells expressing low levels of pancreatic polypeptide (PP) and increased levels of vimentin. Conclusions: 12-LO expression colocalizes within a specific type of islet PP+ cell under prediabetic and diabetic conditions. The costaining of PP and vimentin suggests that 12-LO participates in the process leading to β-cell dedifferentiation in the islet.

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Genome-Wide DNA Methylation Analysis of Human Pancreatic Islets from Type 2 Diabetic and Non-Diabetic Donors Identifies Candidate Genes That Influence Insulin Secretion

PLoS Genetics ◽

10.1371/journal.pgen.1004160 ◽

2014 ◽

Vol 10 (3) ◽

pp. e1004160 ◽

Cited By ~ 259

Author(s):

Tasnim Dayeh ◽

Petr Volkov ◽

Sofia Salö ◽

Elin Hall ◽

Emma Nilsson ◽

...

Keyword(s):

Dna Methylation ◽

Insulin Secretion ◽

Pancreatic Islets ◽

Candidate Genes ◽

Methylation Analysis ◽

Human Pancreatic Islets ◽

Genome Wide ◽

Dna Methylation Analysis ◽

Type 2 Diabetic

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MicroRNA-124a is hyperexpressed in type 2 diabetic human pancreatic islets and negatively regulates insulin secretion

Acta Diabetologica ◽

10.1007/s00592-014-0675-y ◽

2014 ◽

Vol 52 (3) ◽

pp. 523-530 ◽

Cited By ~ 75

Author(s):

Guido Sebastiani ◽

Agnese Po ◽

Evelina Miele ◽

Giuliana Ventriglia ◽

Elena Ceccarelli ◽

...

Keyword(s):

Insulin Secretion ◽

Pancreatic Islets ◽

Human Pancreatic Islets ◽

Type 2 Diabetic

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Persistent Infection of Human Pancreatic Islets by Coxsackievirus B Is Associated with Alpha Interferon Synthesis in β Cells

Journal of Virology ◽

10.1128/jvi.74.21.10153-10164.2000 ◽

2000 ◽

Vol 74 (21) ◽

pp. 10153-10164 ◽

Cited By ~ 127

Author(s):

Wassim Chehadeh ◽

Julie Kerr-Conte ◽

François Pattou ◽

Gunar Alm ◽

Jean Lefebvre ◽

...

Keyword(s):

Pancreatic Islets ◽

Islet Cells ◽

Human Islets ◽

Adult Brain ◽

Viral Rna ◽

Alpha Interferon ◽

Β Cells ◽

Human Pancreatic Islets ◽

Reverse Transcription Pcr ◽

Vp1 Capsid Protein

ABSTRACT The interactions of coxsackievirus B3 (CVB3), CVB4E2 (diabetogenic), and CVB4JBV (nondiabetogenic) strains with human pancreatic islets from eight adult brain-dead donors were investigated. Persistent replication of viruses in human islets was proved by detection of viral RNA by in situ hybridization, VP1 capsid protein by immunofluorescence (IF) staining, negative-strand viral RNA by reverse transcription-PCR in extracted RNA from islets, and release of infectious particles up to 30 days after infection without obvious cytolysis. By double IF staining, glucagon-containing α cells and insulin-containing β cells were shown to be susceptible to CVB. The persistence of CVB3 and CVB4 in islet cells was associated with the chronic synthesis of alpha interferon (IFN-α), as evidenced by the detection of IFN-α mRNA and immunoreactive IFN-α with antiviral activity. By double IF staining, IFN-α was detected in insulin-producing β cells only. Experiments with neutralizing anti-coxsackievirus and adenovirus receptor (CAR) antibodies provided evidence that CAR was expressed by α and β cells and that it played a role in the infection of these cells with CVB and the consecutive IFN-α expression in β cells. The viral replication and the expression of IFN-α in islets were not restricted to the CVB4E2 diabetogenic strain and did not depend on the genetic background of the host. The neutralization of endogenous IFN-α significantly enhanced the CVB replication in islet cells and resulted in rapid destruction of islets. Thus, human β cells can harbor a persistent CVB infection, and CVB-induced IFN-α plays a role in the initiation and/or maintenance of chronic CVB infection in human islets.

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MicroRNA miR-124a, a negative regulator of insulin secretion, is hyperexpressed in human pancreatic islets of type 2 diabetic patients

RNA & DISEASE ◽

10.14800/rd.593 ◽

2015 ◽

Cited By ~ 3

Keyword(s):

Insulin Secretion ◽

Pancreatic Islets ◽

Negative Regulator ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Human Pancreatic Islets ◽

Type 2 Diabetic

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2094-P: Effects of Irisin on Human Pancreatic Islets from Type 2 Diabetic Subjects

Diabetes ◽

10.2337/db20-2094-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 2094-P

Author(s):

NICOLA MARRANO ◽

ANNALISA NATALICCHIO ◽

GIUSEPPINA BIONDI ◽

ANGELO CIGNARELLI ◽

LEONARDO VINCENTI ◽

...

Keyword(s):

Pancreatic Islets ◽

Human Pancreatic Islets ◽

Type 2 Diabetic

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Using single-nucleus RNA-sequencing to interrogate transcriptomic profiles of archived human pancreatic islets

Genome Medicine ◽

10.1186/s13073-021-00941-8 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Giorgio Basile ◽

Sevim Kahraman ◽

Ercument Dirice ◽

Hui Pan ◽

Jonathan M. Dreyfuss ◽

...

Keyword(s):

Pancreatic Islets ◽

Rna Sequencing ◽

Islet Cells ◽

Strong Association ◽

Cell Types ◽

Human Islets ◽

Human Islet ◽

Human Pancreatic Islets ◽

Single Nucleus ◽

Type Gene

Abstract Background Human pancreatic islets are a central focus of research in metabolic studies. Transcriptomics is frequently used to interrogate alterations in cultured human islet cells using single-cell RNA-sequencing (scRNA-seq). We introduce single-nucleus RNA-sequencing (snRNA-seq) as an alternative approach for investigating transplanted human islets. Methods The Nuclei EZ protocol was used to obtain nuclear preparations from fresh and frozen human islet cells. Such preparations were first used to generate snRNA-seq datasets and compared to scRNA-seq output obtained from cells from the same donor. Finally, we employed snRNA-seq to obtain the transcriptomic profile of archived human islets engrafted in immunodeficient animals. Results We observed virtually complete concordance in identifying cell types and gene proportions as well as a strong association of global and islet cell type gene signatures between scRNA-seq and snRNA-seq applied to fresh and frozen cultured or transplanted human islet samples. Conclusions We propose snRNA-seq as a reliable strategy to probe transcriptomic profiles of freshly harvested or frozen sources of transplanted human islet cells especially when scRNA-seq is not ideal.

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