Expression of murine STF-1, a putative insulin gene transcription factor, in beta cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny

Development ◽  
1995 ◽  
Vol 121 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Y. Guz ◽  
M.R. Montminy ◽  
R. Stein ◽  
J. Leonard ◽  
L.W. Gamer ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Beta Cell ◽  
Cell Fate ◽  
Beta Cells ◽  
Protein S ◽  
Cell Types ◽  
Homeodomain Protein ◽  
Pancreatic Cell ◽  
Precursor Pool ◽  
Islet Cell Types

The XlHbox 8 homeodomain protein of Xenopus and STF-1, its mammalian homolog, are selectively expressed by beta cells of adult mouse pancreatic islets, where they are likely to regulate insulin expression. We sought to determine whether the expression of the homeobox protein/s during mouse embryonic development was specific to beta cells or, alternatively, whether XlHbox 8/STF-1 protein/s were initially expressed by multipotential precursors and only later became restricted to the insulin-containing cells. With two antibodies, we studied the localization of STF-1 during murine pancreatic development. In embryos, as in adults, STF-1 was expressed by most beta cells, by subsets of the other islet cell types and by mucosal epithelial cells of the duodenum. In addition, most epithelial cells of the pancreatic duct and exocrine cells of the pancreas transiently contained STF-1. We conclude that in mouse, STF-1 not only labels a domain of intestinal epithelial cells but also provides a spatial and temporal marker of endodermal commitment to a pancreatic and subsequently, to an endocrine beta cell fate. We propose a model of pancreatic cell development that suggests that exocrine and endocrine (alpha, beta, delta and PP) cells arise from a common precursor pool of STF-1+ cells and that progression towards a defined monospecific non-beta cell type is correlated with loss of STF-1 expression.

scholarly journals The absence of H-2 antigens from mouse pancreatic beta-cells demonstrated by immunoferritin labeling.

1979 ◽  
Vol 150 (1) ◽  
pp. 1-9 ◽  
Author(s):  
E L Parr
Keyword(s):  
Endothelial Cells ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Beta Cell ◽  
Pancreatic Duct ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Acinar Cells ◽  
Cell Types ◽  
Capillary Endothelial Cells

Islets of Langerhans were isolated from mouse pancreases and fixed in periodatelysine-paraformaldehyde. The fixed islets were then dissociated with trypsin and EDTA to yield cell suspensions that contained mainly four cell types; beta-cells, capillary endothelial cells, acinar cells, and pancreatic duct epithelial cells. The nonislet cells were probably associated wtih the surface of the isolated islets. The H-2 antigens of the dissociated pancreatic cells were labeled with an immunoferritin technique. Pancreatic duct epithelial cells showed specific ferritin labeling on their lateral cell membranes but not on apical microvillus membranes. Acinar cells were also labeled on lateral membranes, and the capillary endothelial cells were labeled on both the luminal and albuminal aspects of their surface membranes. In contrast, pancreatic beta-cells were unlabeled. The number of ferritin molecules per unit length of beta-cell membrane was essentially the same on cells from the antigenic strain and the congeneic control strain, and was about 200-fold less than on the labeled pancreatic duct epithelial cell lateral membranes. Pancreatic beta-cells are therefore one of six known epithelial cell types on which H-2 antigens can not be detected by immunoferritin labeling. The apparent absence of H-2 antigens from these cells suggests a study of the viability of beta-cells in allografts of dissociated islet cells, in which the beta-cell would not be in contact with antigenic cells. Such studies might lead to a new approach to the control of diabetes mellitus by transplantation.

scholarly journals The pancreatic beta cell: an intricate relation between anatomical structure, the signalling mechanism of glucose-induced insulin secretion, the low antioxidative defence, the high vulnerability and sensitivity to diabetic stress

ChemTexts ◽  
2021 ◽  
Vol 7 (2) ◽  
Author(s):  
Sigurd Lenzen
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Islet Cell ◽  
Pancreatic Beta Cell ◽  
Cell Types ◽  
Antioxidative Defence ◽  
Islet Cell Types ◽  
Low Expression

AbstractThe biosynthesis of insulin takes place in the insulin-producing beta cells that are organized in the form of islets of Langerhans together with a few other islet cell types in the pancreas organ. The signal for glucose-induced insulin secretion is generated in two pathways in the mitochondrial metabolism of the pancreatic beta cells. These pathways are also known as the triggering pathway and the amplifying pathway. Glucokinase, the low-affinity glucose-phosphorylating enzyme in beta cell glycolysis acts as the signal-generating enzyme in this process. ATP ultimately generated is the crucial second messenger in this process. Insulin-producing pancreatic beta cells are badly protected against oxidative stress resulting in a particular vulnerability of this islet cell type due to low expression of H2O2-inactivating enzymes in various subcellular locations, specifically in the cytosol, mitochondria, peroxisomes and endoplasmic reticulum. This is in contrast to the glucagon-producing alpha cells and other islet cell types in the islets that are well equipped with these H2O2-inactivating enzymes. On the other hand the membranes of the pancreatic beta cells are well protected against lipid peroxidation and ferroptosis through high level expression of glutathione peroxidase 4 (GPx4) and this again is at variance from the situation in the non-beta cells of the islets with a low expression level of GPx4. The weak antioxidative defence equipment of the pancreatic beta cells, in particular in states of disease, is very dangerous because the resulting particular vulnerability endangers the functionality of the beta cells, making people prone to the development of a diabetic metabolic state.

scholarly journals Aging of human endocrine pancreatic cell types is heterogeneous and sex-specific

2019 ◽  
Author(s):  
Rafael Arrojo e Drigo ◽  
Galina Erikson ◽  
Swati Tyagi ◽  
Juliana Capitanio ◽  
James Lyon ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Endocrine Pancreas ◽  
Cell Function ◽  
Meta Analysis ◽  
Cell Types ◽  
Pancreatic Cell ◽  
Transcriptional Signature ◽  
Human Lifespan ◽  
Functional Analyses

SummaryThe human endocrine pancreas must regulate glucose homeostasis throughout the human lifespan, which is generally decades. We performed meta-analysis of single-cell, RNA-sequencing datasets derived from 36 individuals, as well as functional analyses, to characterize age-associated changes to the major endocrine pancreatic cell types. Increasing age was associated with shifts in pancreatic alpha and beta cell identity and loss of nuclear integrity in non-diabetic humans. In non-diabetic individuals ≥ 50 years old, 80% of their beta cells exhibited a transcriptional signature similar to cells from type-2 diabetic (T2D) donors. Surprisingly, ∼5% of beta cells from T2D donors retained a youthful, N.D. transcriptional profile. Furthermore, beta cell function was reduced by 50% during aging in men but not women, which may explain sex-associated differences in diabetes etiology. These analyses reveal that aging of the human endocrine pancreas is sex- and cell-type specific.

scholarly journals Protein-Mediated Interactions of Pancreatic Islet Cells

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-22 ◽  
Author(s):  
Paolo Meda
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Islet Cell ◽  
Islet Cells ◽  
Cell Communication ◽  
Cell Types ◽  
Integral Membrane Protein ◽  
Normal Function ◽  
Cell Functions ◽  
Islet Cell Types

The islets of Langerhans collectively form the endocrine pancreas, the organ that is soley responsible for insulin secretion in mammals, and which plays a prominent role in the control of circulating glucose and metabolism. Normal function of these islets implies the coordination of different types of endocrine cells, noticeably of the beta cells which produce insulin. Given that an appropriate secretion of this hormone is vital to the organism, a number of mechanisms have been selected during evolution, which now converge to coordinate beta cell functions. Among these, several mechanisms depend on different families of integral membrane proteins, which ensure direct (cadherins, N-CAM, occludin, and claudins) and paracrine communications (pannexins) between beta cells, and between these cells and the other islet cell types. Also, other proteins (integrins) provide communication of the different islet cell types with the materials that form the islet basal laminae and extracellular matrix. Here, we review what is known about these proteins and their signaling in pancreaticβ-cells, with particular emphasis on the signaling provided by Cx36, given that this is the integral membrane protein involved in cell-to-cell communication, which has so far been mostly investigated for effects on beta cell functions.

scholarly journals Group B Coxsackievirus Diabetogenic Phenotype Correlates with Replication Efficiency

2006 ◽  
Vol 80 (11) ◽  
pp. 5637-5643 ◽  
Author(s):  
Toru Kanno ◽  
Kisoon Kim ◽  
Ken Kono ◽  
Kristen M. Drescher ◽  
Nora M. Chapman ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Cultures ◽  
Virulent Strain ◽  
Nod Mice ◽  
Cell Types ◽  
Rapid Onset ◽  
Infectious Dose ◽  
Group B ◽  
Islet Cell Types

ABSTRACT Group B coxsackieviruses can initiate rapid onset type 1 diabetes (T1D) in old nonobese diabetic (NOD) mice. Inoculating high doses of poorly pathogenic CVB3/GA per mouse initiated rapid onset T1D. Viral protein was detectable in islets shortly after inoculation in association with beta cells as well as other primary islet cell types. The virulent strain CVB3/28 replicated to higher titers more rapidly than CVB3/GA in the pancreas and in established beta cell cultures. Exchange of 5′-nontranslated regions between the two CVB3 strains demonstrated a variable impact on replication in beta cell cultures and suppression of in vivo replication for both strains. While any CVB strain may be able to induce T1D in prediabetic NOD mice, T1D onset is linked both to the viral replication rate and infectious dose.

scholarly journals Flavonoids Identification and Pancreatic Beta-Cell Protective Effect of Lotus Seedpod

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 658 ◽  
Author(s):  
Ming-Shih Lee ◽  
Charng-Cherng Chyau ◽  
Chi-Ping Wang ◽  
Ting-Hsuan Wang ◽  
Jing-Hsien Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Injury ◽  
Pancreatic Beta Cell ◽  
B Cell Lymphoma ◽  
Pancreatic Cell ◽  
Traditional Chinese Herbal Medicine ◽  
Lotus Seedpod

Oxidative stress is highly associated with the development of diabetes mellitus (DM), especially pancreatic beta-cell injury. Flavonoids derived from plants have caused important attention in the prevention or treatment of DM. Lotus seedpod belongs to a traditional Chinese herbal medicine and has been indicated to possess antioxidant, anti-age, anti-glycative, and hepatoprotective activities. The purpose of this study was to demonstrate the pancreatic beta-cell protective effects of lotus seedpod aqueous extracts (LSE) against oxidative injury. According to HPLC/ESI-MS-MS method, LSE was confirmed to have flavonoids derivatives, especially quercetin-3-glucuronide (Q3G). In vitro, LSE dose-dependently improved the survival and function of rat pancreatic beta-cells (RIN-m5F) from hydrogen peroxide (H2O2)-mediated loss of cell viability, impairment of insulin secretion, and promotion of oxidative stress. LSE showed potential in decreasing the H2O2-induced occurrence of apoptosis. In addition, H2O2-triggered acidic vesicular organelle formation and microtubule-associated protein light chain 3 (LC3)-II upregulation, markers of autophagy, were increased by LSE. Molecular data explored that antiapoptotic and autophagic effects of LSE, comparable to that of Q3G, might receptively be mediated via phospho-Bcl-2-associated death promoter (p-Bad)/B-cell lymphoma 2 (Bcl-2) and class III phosphatidylinositol-3 kinase (PI3K)/LC3-II signal pathway. In vivo, LSE improved the DM symptoms and pancreatic cell injury better than metformin, a drug that is routinely prescribed to treat DM. These data implied that LSE induces the autophagic signaling, leading to protect beta-cells from oxidative stress-related apoptosis and injury.

scholarly journals A Role for Activin A and Betacellulin in Human Fetal Pancreatic Cell Differentiation and Growth1

2000 ◽  
Vol 85 (10) ◽  
pp. 3892-3897 ◽  
Author(s):  
Carla Demeterco ◽  
Gillian M. Beattie ◽  
Sergio Atala Dib ◽  
Ana D. Lopez ◽  
Alberto Hayek
Keyword(s):  
Epithelial Cells ◽  
Primary Cultures ◽  
Fold Increase ◽  
Cell Types ◽  
Activin A ◽  
Pancreatic Tissue ◽  
Pancreatic Cell ◽  
Endocrine Differentiation ◽  
Epidermal Growth ◽  
Regulation Of Growth

Activin A (Act.A), a member of the transforming growth factorβ family of secreted proteins, has been implicated in the regulation of growth and differentiation of various cell types. Betacellulin (BTC), a member of the epidermal growth factor family, converts exocrine AR42J cells to insulin-expressing cells when combined with Act.A. We have used primary cultures of human fetal pancreatic tissue to identify the effects of Act.A and/or BTC on islet development and growth. Exposure to Act.A resulted in a 1.5-fold increase in insulin content (P < 0.005) and a 2-fold increase in the number of cells immunopositive for insulin (P < 0.005). The formation of islet-like cell clusters, containing mainly epithelial cells, during a 5-day culture, was stimulated 1.4-fold by BTC (P < 0.05). BTC alone caused a 2.6-fold increase in DNA synthesis (P < 0.005). These data suggest that Act.A induces endocrine differentiation, whereas BTC has a mitogenic effect on human undifferentiated pancreatic epithelial cells.

scholarly journals KSA Antigen Ep-CAM Mediates Cell–Cell Adhesion of Pancreatic Epithelial Cells: Morphoregulatory Roles in Pancreatic Islet Development

1998 ◽  
Vol 140 (6) ◽  
pp. 1519-1534 ◽  
Author(s):  
V. Cirulli ◽  
L. Crisa ◽  
G.M. Beattie ◽  
M.I. Mally ◽  
A.D. Lopez ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Growth ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Fate ◽  
Pancreatic Islet ◽  
Pancreatic Cell ◽  
Cell Clusters ◽  
Endocrine Differentiation ◽  
Cell Cell

Cell adhesion molecules (CAMs) are important mediators of cell–cell interactions and regulate cell fate determination by influencing growth, differentiation, and organization within tissues. The human pancarcinoma antigen KSA is a glycoprotein of 40 kD originally identified as a marker of rapidly proliferating tumors of epithelial origin. Interestingly, most normal epithelia also express this antigen, although at lower levels, suggesting that a dynamic regulation of KSA may occur during cell growth and differentiation. Recently, evidence has been provided that this glycoprotein may function as an epithelial cell adhesion molecule (Ep-CAM). Here, we report that Ep-CAM exhibits the features of a morphoregulatory molecule involved in the development of human pancreatic islets. We demonstrate that Ep-CAM expression is targeted to the lateral domain of epithelial cells of the human fetal pancreas, and that it mediates calcium-independent cell–cell adhesion. Quantitative confocal immunofluorescence in fetal pancreata identified the highest levels of Ep-CAM expression in developing islet-like cell clusters budding from the ductal epithelium, a cell compartment thought to comprise endocrine progenitors. A surprisingly reversed pattern was observed in the human adult pancreas, displaying low levels of Ep-CAM in islet cells and high levels in ducts. We further demonstrate that culture conditions promoting epithelial cell growth induce upregulation of Ep-CAM, whereas endocrine differentiation of fetal pancreatic epithelial cells, transplanted in nude mice, is associated with a downregulation of Ep-CAM expression. In addition, a blockade of Ep-CAM function by KS1/4 mAb induced insulin and glucagon gene transcription and translation in fetal pancreatic cell clusters. These results indicate that developmentally regulated expression and function of Ep-CAM play a morphoregulatory role in pancreatic islet ontogeny.

scholarly journals Alpha cell regulation of beta cell function

Diabetologia ◽  
2020 ◽  
Vol 63 (10) ◽  
pp. 2064-2075
Author(s):  
Tilo Moede ◽  
Ingo B. Leibiger ◽  
Per-Olof Berggren
Keyword(s):  
Blood Glucose ◽  
Beta Cell ◽  
Beta Cells ◽  
Endocrine Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Cell Types ◽  
Alpha Cell ◽  
Alpha Cells

Abstract The islet of Langerhans is a complex endocrine micro-organ consisting of a multitude of endocrine and non-endocrine cell types. The two most abundant and prominent endocrine cell types, the beta and the alpha cells, are essential for the maintenance of blood glucose homeostasis. While the beta cell produces insulin, the only blood glucose-lowering hormone of the body, the alpha cell releases glucagon, which elevates blood glucose. Under physiological conditions, these two cell types affect each other in a paracrine manner. While the release products of the beta cell inhibit alpha cell function, the alpha cell releases factors that are stimulatory for beta cell function and increase glucose-stimulated insulin secretion. The aim of this review is to provide a comprehensive overview of recent research into the regulation of beta cell function by alpha cells, focusing on the effect of alpha cell-secreted factors, such as glucagon and acetylcholine. The consequences of differences in islet architecture between species on the interplay between alpha and beta cells is also discussed. Finally, we give a perspective on the possibility of using an in vivo imaging approach to study the interactions between human alpha and beta cells under in vivo conditions.

scholarly journals Detection of Amplifiable mRNA Extracellular to Insulin-Producing Cells: Potential for Predicting Beta Cell Mass and Function

2007 ◽  
Vol 53 (11) ◽  
pp. 1936-1944 ◽  
Author(s):  
Sweta Rani ◽  
Martin Clynes ◽  
Lorraine O’Driscoll
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Cell Types ◽  
Cell Number ◽  
Reverse Transcription Pcr ◽  
Insulin Producing Cells ◽  
And Function ◽  
B1 Cells

Abstract Background: Detecting extracellular nucleic acids in the serum/plasma of cancer patients may help in cancer diagnosis. We investigated whether extracellular mRNAs are reproducibly detectable in conditioned medium (CM) from insulin-producing cell cultures and if their presence and amounts are indicative of cell number and/or function. Methods: We isolated mRNA from medium conditioned by the culture of several insulin-producing cell types: MIN6(L) (glucose-responsive), MIN6(H) (glucose-nonresponsive), and MIN6 B1 murine beta cells and monkey kidney fibroblast cells engineered to produce human preproinsulin (PPI) (Vero-PPI). We used reverse transcription–PCR analyses to evaluate the occurrence of several mRNAs and investigated whether the presence and amounts of the various extracellular mRNAs are associated with cell mass and/or function. Results: Reproducible amplification of mRNAs encoded by Pdx1, Npy, Egr1, Pld1, Chgb, Ins1, Ins2, and Actb from MIN6(L), MIN6(H), and MIN6 B1 cells and their CM suggests that beta cells transcribe and release these mRNAs into their culture environment. Similarly, PPI mRNA was detected in samples of Vero-PPI cells and CM. The amounts of some mRNAs reflected the numbers and functional status (i.e., glucose responsiveness vs nonresponsiveness) of the cells conditioning the medium. Although Pax4 mRNA was detected in the MIN6 B1 cell line, the fact that this transcript was not amplifiable from the corresponding CM suggested that mRNA release was selective. Conclusion: mRNAs may be secreted from insulin-producing cells, are reproducibly detected in the extracellular environment, and may have potential as extracellular biomarkers for assessing beta cell mass and function.

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