scholarly journals Molecular and genetic regulation of pig pancreatic islet cell development

2019 ◽  
Author(s):  
Seokho Kim ◽  
Robert L. Whitener ◽  
Heshan Peiris ◽  
Xueying Gu ◽  
Charles A. Chang ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Developmental Stages ◽  
Islet Cells ◽  
Genetic Regulation ◽  
Human Islets ◽  
Human Islet ◽  
Human Pancreas ◽  
Pancreatic Islet Cell ◽  
Characteristic Features ◽  
Specific Regulation

AbstractReliance on rodents for understanding pancreatic genetics, development and islet function could limit progress in developing interventions for human diseases like diabetes mellitus. Similarities of pancreas morphology and function suggest that porcine and human pancreas developmental biology may have useful homologies. However, little is known about pig pancreas development. To fill this knowledge gap, we investigated fetal and neonatal pig pancreas at multiple, crucial developmental stages using modern experimental approaches. Purification of islet β-, α- and δ-cells followed by transcriptome analysis (RNA-Seq) and immunohistology identified cell- and stage-specific regulation, and revealed that pig and human islet cells share characteristic features not observed in mice. Morphometric analysis also revealed endocrine cell allocation and architectural similarities between pig and human islets. Our analysis unveiled scores of signaling pathways linked to native islet β-cell functional maturation, including evidence of fetal α-cell GLP-1 production and signaling to β-cells. Thus, the findings and resources detailed here show how pig pancreatic islet studies complement other systems for understanding the developmental programs that generate functional islet cells, and that are relevant to human pancreatic diseases.Summary StatementThis study reveals transcriptional, signaling and cellular programs governing pig pancreatic islet development, including striking similarities to human islet ontogeny, providing a novel resource for advancing human islet replacement strategies.

Silver Staining of Pancreatic Islets as Revealed by Electron Microscopy

1967 ◽  
Vol 25 ◽  
pp. 44-45
Author(s):  
Kazuaki Misugi ◽  
Nobuko Misugi ◽  
Hiroshi Yamada
Keyword(s):  
Pancreatic Islet ◽  
Silver Staining ◽  
Islet Cells ◽  
Severe Hypoglycemia ◽  
Granular Cell ◽  
Electron Microscopic Level ◽  
Staining Reaction ◽  
Electron Microscopic ◽  
Pancreatic Islet Cell ◽  
D Cell

The authors had described the fine structure of a type of pancreatic islet cell, which appeared different from typical alpha and beta cells, and tentatively considered that this third type of granular cell probably represents the D cell (Figure 1).Since silver staining has been widely used to differentiate different types of pancreatic islet cells by light microscopy, an attempt to examine this staining reaction at the electron microscopic level was made.Material and Method: Surgically removed specimens from three infants who suffered from severe hypoglycemia were used. The specimens were fixed and preserved in 20% neutral formalin. Frozen sections, 30 to 40 micron thick, were prepared and they were stained by Bielschowsky's method as modified by Suzuki (2). The stained sections were examined under a microscope and islet tissues were isolated. They were fixed in 1% osmium tetroxide in phosphate buffer for one hour and embedded in Epon 812 following dehydration through a series of alcohols and propylene oxide.

scholarly journals Immunohistochemistry of Pancreatic Islet Cell Tumors in the Ferret (Mustela putorius furo)

1997 ◽  
Vol 34 (5) ◽  
pp. 387-393 ◽  
Author(s):  
G. A. Andrews ◽  
N. C. Myers ◽  
C. Chard-Bergstrom
Keyword(s):  
Pancreatic Islets ◽  
Pancreatic Islet ◽  
Pancreatic Polypeptide ◽  
Islet Cell ◽  
Islet Cells ◽  
Neuron Specific Enolase ◽  
Islet Cell Tumors ◽  
Pancreatic Islet Cell ◽  
Formalin Fixed Paraffin Embedded ◽  
Pancreatic Islet Cell Tumors

Twenty-two pancreatic islet cell tumors and normal pancreatic islets from ferrets were evaluated by immunohistochemistry for expression of the peptide hormones insulin, somatostatin, glucagon, and pancreatic polypeptide (PP) and the neuroendocrine markers chromogranin A (CgA) and neuron-specific enolase (NSE). In normal pancreatic islets, the majority of cells stained strongly with CgA and NSE. A cells, B cells, D cells, and PP cells stained strongly with glucagon, insulin, somatostatin, and PP, respectively. All 22 tumors stained with CgA and NSE. The proportion of cells within tumors staining for CgA was variable, but more than half of the cells stained positively in 18 of the tumors. The intensity of staining for CgA was strong (reactivity equivalent to or greater than normal islet cells in adjacent tissue) in 11 moderate in six, and weak in five of the tumors. All tumors stained for NSE, with ≥50% of the cells staining in 21 of the tumors, and the intensity of staining was strong in 18 of the tumors. Twenty of 22 tumors stained positively for insulin, with ≥50% of the cells staining in 19 of them. The intensity of staining for insulin was strong in 12, moderate in seven, and weak in one of the tumors. Approximately ≤1% of the cells in 15 of 22 tumors stained for somatostatin, five tumors stained for pancreatic polypeptide, and three tumors stained for glucagon. These data indicate that the majority of islet cell tumors of ferrets express immunohistochemically detectable insulin. CgA and NSE are both useful general markers for such tumors, including those that are insulin negative. Commercially available antisera to CgA, NSE, insulin, glucagon, somatostatin, and PP work well in formalin-fixed, paraffin-embedded tissue for immunophenotyping islet cell tumors in the ferret.

Transcriptional activation of the rat glucagon gene by the cyclic AMP-responsive element in pancreatic islet cells

1990 ◽  
Vol 10 (12) ◽  
pp. 6799-6804
Author(s):  
W Knepel ◽  
J Chafitz ◽  
J F Habener
Keyword(s):  
Cyclic Amp ◽  
Pancreatic Islet ◽  
Transcriptional Activation ◽  
Islet Cells ◽  
Pancreatic Islet Cell ◽  
Heterologous Promoter ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Flanking Region ◽  
Responsive Element

The 5'-flanking region of the rat glucagon gene contains, from nucleotides -291 to -298, a sequence (TGA CGTCA) which mediates cyclic AMP (cAMP) responsiveness in several genes (cAMP-responsive element [CRE]). However, because of nonpermissive bases surrounding the CRE octamer, the glucagon CRE does not confer cAMP responsiveness to an inert heterologous promoter in placental JEG cells that do not express the glucagon gene. This report describes transient transfection experiments with glucagon-reporter fusion genes that show that glucagon gene expression is activated by cAMP-dependent protein kinase A in a glucagon-expressing pancreatic islet cell line. This activation is mediated through the glucagon CRE.

scholarly journals Molecular and genetic regulation of pig pancreatic islet cell development

Development ◽  
2020 ◽  
Vol 147 (6) ◽  
pp. dev186213 ◽  
Author(s):  
Seokho Kim ◽  
Robert L. Whitener ◽  
Heshan Peiris ◽  
Xueying Gu ◽  
Charles A. Chang ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Islet Cell ◽  
Genetic Regulation ◽  
Cell Development ◽  
Pancreatic Islet Cell

scholarly journals Transcriptional activation of the rat glucagon gene by the cyclic AMP-responsive element in pancreatic islet cells.

1990 ◽  
Vol 10 (12) ◽  
pp. 6799-6804 ◽  
Author(s):  
W Knepel ◽  
J Chafitz ◽  
J F Habener
Keyword(s):  
Cyclic Amp ◽  
Pancreatic Islet ◽  
Transcriptional Activation ◽  
Islet Cells ◽  
Pancreatic Islet Cell ◽  
Heterologous Promoter ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Flanking Region ◽  
Responsive Element

The 5'-flanking region of the rat glucagon gene contains, from nucleotides -291 to -298, a sequence (TGA CGTCA) which mediates cyclic AMP (cAMP) responsiveness in several genes (cAMP-responsive element [CRE]). However, because of nonpermissive bases surrounding the CRE octamer, the glucagon CRE does not confer cAMP responsiveness to an inert heterologous promoter in placental JEG cells that do not express the glucagon gene. This report describes transient transfection experiments with glucagon-reporter fusion genes that show that glucagon gene expression is activated by cAMP-dependent protein kinase A in a glucagon-expressing pancreatic islet cell line. This activation is mediated through the glucagon CRE.

scholarly journals Interleukin-22 reverses human islet dysfunction and apoptosis triggered by hyperglycemia and LIGHT

2018 ◽  
Vol 60 (3) ◽  
pp. 171-183
Author(s):  
Shadab Abadpour ◽  
Bente Halvorsen ◽  
Afaf Sahraoui ◽  
Olle Korsgren ◽  
Pål Aukrust ◽  
...  
Keyword(s):  
Islet Cells ◽  
Harmful Effect ◽  
Human Islets ◽  
Protective Role ◽  
Human Islet ◽  
Islet Function ◽  
Post Transplantation ◽  
Interleukin 22 ◽  
Glucose Stimulated Insulin Secretion

Interleukin (IL)-22 has recently been suggested as an anti-inflammatory cytokine that could protect the islet cells from inflammation- and glucose-induced toxicity. We have previously shown that the tumor necrosis factor family member, LIGHT, can impair human islet function at least partly via pro-apoptotic effects. Herein, we aimed to investigate the protective role of IL-22 on human islets exposed to the combination of hyperglycemia and LIGHT. First, we found upregulation of LIGHT receptors (LTβR and HVEM) in engrafted human islets exposed to hyperglycemia (>11 mM) for 17 days post transplantation by using a double islet transplantation mouse model as well as in human islets cultured with high glucose (HG) (20 mM glucose) + LIGHT in vitro, and this latter effect was attenuated by IL-22. The effect of HG + LIGHT impairing glucose-stimulated insulin secretion was reversed by IL-22. The harmful effect of HG + LIGHT on human islet function seemed to involve enhanced endoplasmic reticulum stress evidenced by upregulation of p-IRE1α and BiP, elevated secretion of pro-inflammatory cytokines (IL-6, IL-8, IP-10 and MCP-1) and the pro-coagulant mediator tissue factor (TF) release and apoptosis in human islets, whereas all these effects were at least partly reversed by IL-22. Our findings suggest that IL-22 could counteract the harmful effects of LIGHT/hyperglycemia on human islet cells and potentially support the strong protective effect of IL-22 on impaired islet function and survival.

scholarly journals The islet ghrelin cell

2013 ◽  
Vol 52 (1) ◽  
pp. R35-R49 ◽  
Author(s):  
Nils Wierup ◽  
Frank Sundler ◽  
R Scott Heller
Keyword(s):  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Developmental Regulation ◽  
Genetic Regulation ◽  
Cell Types ◽  
Human Islets ◽  
Histochemical Staining ◽  
Pancreatic Tumours ◽  
Age Related ◽  
Staining Methods

The islets of Langerhans are key regulators of glucose homeostasis and have been known as a structure for almost one and a half centuries. During the twentieth century several different cell types were described in the islets of different species and at different developmental stages. Six cell types with identified hormonal product have been described so far by the use of histochemical staining methods, transmission electron microscopy, and immunohistochemistry. Thus, glucagon-producing α-cells, insulin-producing β-cells, somatostatin-producing δ-cells, pancreatic polypeptide-producing PP-cells, serotonin-producing enterochromaffin-cells, and gastrin-producing G-cells have all been found in the mammalian pancreas at least at some developmental stage. Species differences are at hand and age-related differences are also to be considered. Eleven years ago a novel cell type, the ghrelin cell, was discovered in the human islets. Subsequent studies have shown the presence of islet ghrelin cells in several animals, including mouse, rat, gerbils, and fish. The developmental regulation of ghrelin cells in the islets of mice has gained a lot of interest and several studies have added important pieces to the puzzle of molecular mechanisms and the genetic regulation that lead to differentiation into mature ghrelin cells. A body of evidence has shown that ghrelin is an insulinostatic hormone, and the potential for blockade of ghrelin signalling as a therapeutic avenue for type 2 diabetes is intriguing. Furthermore, ghrelin-expressing pancreatic tumours have been reported and ghrelin needs to be taken into account when diagnosing pancreatic tumours. In this review article, we summarise the knowledge about islet ghrelin cells obtained so far.

scholarly journals SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 are Expressed in the Pancreas but are Not Enriched in Islet Endocrine Cells

2020 ◽  
Author(s):  
Katie C. Coate ◽  
Jeeyeon Cha ◽  
Shristi Shrestha ◽  
Wenliang Wang ◽  
Luciana Mateus Gonçalves ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Endocrine Cells ◽  
Islet Cells ◽  
Cell Entry ◽  
Pancreatic Ducts ◽  
Human Pancreas ◽  
Β Cells ◽  
Ductal Cells ◽  
Putative Receptor ◽  
New Onset

Summary/AbstractReports of new-onset diabetes and diabetic ketoacidosis in individuals with COVID-19 have led to the hypothesis that SARS-CoV-2, the virus that causes COVID-19, is directly cytotoxic to pancreatic islet β cells. This would require binding and entry of SARS-CoV-2 into host β cells via cell surface co-expression of ACE2 and TMPRSS2, the putative receptor and effector protease, respectively. To define ACE2 and TMPRSS2 expression in the human pancreas, we examined six transcriptional datasets from primary human islet cells and assessed protein expression by immunofluorescence in pancreata from donors with and without diabetes. ACE2 and TMPRSS2 transcripts were low or undetectable in pancreatic islet endocrine cells as determined by bulk or single cell RNA sequencing, and neither protein was detected in α or β cells from these donors. Instead, ACE2 protein was expressed in the islet and exocrine tissue microvasculature and also found in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. The absence of significant ACE2 and TMPRSS2 co-expression in islet endocrine cells reduces the likelihood that SARS-CoV-2 directly infects pancreatic islet β cells through these cell entry proteins.

scholarly journals Pancreatic islet cell autophagy during aging in rats

2013 ◽  
Vol 36 (2) ◽  
pp. 72 ◽  
Author(s):  
Shuang Wang ◽  
Qian-qian Sun ◽  
Bing Xiang ◽  
Xiu-Jun Li
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Pancreatic Islet ◽  
Islet Cell ◽  
Islet Cells ◽  
Cell Structure ◽  
Fasting Blood Glucose ◽  
Pancreatic Islet Cell ◽  
Pancreatic Cell ◽  
Old Rats

Purpose: Autophagy induces pancreatic β cell death. The purpose of the present study was to examine the hypothesis that the extent of pancreatic autophagy is associated with aging and age-related diabetes. Methods: Pancreatic tissue and blood samples were collected from Sprague Dawley rats receiving a normal diet at 2 (the young group), 6 (the adult group), 12 (the middle-age group) and 20-24 (the aged group) months of age. Body weight and fasting blood glucose, serum lipid levels and serum insulin levels were determined. Pancreatic cell structure and autophagy were determined using transmission electron microscopy of rats at 6, 12 and 24 months of age. Lamp2 and LC3b protein expression levels were determined by both immunohistochemistry and Western blot analyses, and islet cell apoptosis was assessed using the TUNEL assay. Results: Fasting blood glucose, triglyceride and FFA levels increased significantly with age (p < 0.05). Compared with levels seen in two-month-old rats, insulin secretion of islet cells in vitro was significantly reduced at 6, 12, and 20 months of age (p < 0.05). Autophagosomes were only observed in islet cells of 24 month-old rats. Increased expression of the autophagic markers, Lamp2 and LC3b, was observed with age. A significant increase in apoptotic index was observed between young rats (two-months-old) and older rats (six-, 12- and 24-months-old), but no differences were observed between rats six, 12 and 24 months of age. Conclusion: Appearance of autophagosomes and increased Lamp2 and LC3b expression in pancreatic islet cells coincided with a significant decrease in insulin secretion and elevation of fasting blood glucose in aged rats.

An experimental investigation into the possible origin of pancreatic islet cells from rhombencephalic neurectoderm

Development ◽  
1979 ◽  
Vol 52 (1) ◽  
pp. 23-38
Author(s):  
Ann Andrew ◽  
Beverley Kramer
Keyword(s):  
Pancreatic Islet ◽  
Islet Cell ◽  
Islet Cells ◽  
Cell Types ◽  
Nuclear Marker ◽  
Electron Microscopic ◽  
Pancreatic Islet Cell ◽  
Enteric Ganglia ◽  
Microscopic Features ◽  
Islet Cell Types

To determine whether or not any pancreatic islet cell type arises from rhombencephalic levels of neurectoderm, lengths of presumptive rhombencephalon (containing potential neural crest) of Black Australorp chick embryos at 6- to 9-somite stages were replaced isotopically and isochronically by neural tube of Japanese quail embryos. Some transplants included mesencephalic regions. In some cases various levels of the rhombencephalon were deleted and not replaced. The quail nuclear marker was detected in cranial ganglia in operated embryos sacrificed at 3¾ days of incubation and in enteric ganglia and cells accompanying some pancreatic nerves, in embryos killed at 7 days of incubation. This provided evidence of normal migration of crest cells from the grafts. Dopa was administered to the younger embryos, which were submitted to the formaldehyde-induced fluorescence procedure to demonstrate APUD (Amine Precursor Uptake and Decarboxylation) cells. No pancreatic APUD cells exhibited the quail nuclear marker. In 9- to 11-day embryos, A and B cells were identified by specific light and electron microscopic features. None showed the quail marker. The marker was also absent from those D cells seen and from cells of an as yet unidentified type, but not enough of these were found to warrant a conclusion. All islet cell types were found in embryos from which various levels of the rhombencephalon had been deleted. It is concluded that at least A and B islet cells are not derived from the rhombencephalic neurectoderm and probably not from mesencephalic levels. Their most likely origin remains the endoderm, which was the accepted source until recently

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