scholarly journals Heterogeneity of chromogranin A-derived peptides in bovine gut, pancreas and adrenal medulla

1991 ◽  
Vol 276 (2) ◽  
pp. 471-479 ◽  
Author(s):  
A Watkinson ◽  
A C Jönsson ◽  
M Davison ◽  
J Young ◽  
C M Lee ◽  
...  
Keyword(s):  
Endocrine Cell ◽  
Cell Biology ◽  
Chromogranin A ◽  
Endocrine Cells ◽  
Cell Types ◽  
Intact Protein ◽  
Pancreatic Endocrine Cells ◽  
Gastric Corpus ◽  
Adrenal Chromaffin ◽  
Bovine Pancreas

Chromogranin A is produced in many endocrine cell types, and is widely used as a marker in endocrine-cell pathology and secretory-cell biology. There is some evidence that it may be proteolytically processed to yield the putative pancreatic regulatory peptide, pancreastatin, and, in order to characterize the relevant pathways in gastrointestinal and pancreatic endocrine cells, we have used, in radioimmunoassay, site-directed antibodies to pancreastatin itself (L331) and to a sequence of chromogranin A immediately C-terminal to pancreastatin (L300). The latter antibody revealed three major forms of immunoreactivity of 8 kDa and five peptides of approx. 3 kDa in bovine pancreas and gut extracts. The 8 kDa peptides were characterized as chromogranin A-(248-313)-peptides, i.e. C-terminally extended forms of pancreastatin; two of the 8 kDa variants differed in two positions, confirming a polymorphism predicted from cDNA sequencing. One of the 3 kDa peptides was characterized as chromogranin A-(297-313)-peptide, i.e. the C-terminal heptadecapeptide of the 8 kDa peptide that would be liberated after cleavage to yield pancreastatin. On the basis of chromatographic studies, immunohistochemistry and the stoichiometry of different immunoreactive peptides, three different pathways of chromogranin A processing were identified: in adrenal chromaffin cells chromogranin A existed mainly as the unmodified intact protein, in pancreatic islet and gastric antral endocrine cells pancreastatin and the 3 kDa peptides were major products, but in small intestine and gastric corpus endocrine cells there was little nor no pancreastatin and the 8 kDa cleavage product predominated. There are therefore important differences in the distribution of chromogranin A-derived peptides between quite closely related populations of endocrine cells that are attributable not only to variable post-translational cleavage but also to the expression of different primary sequences. It seems possible that in different cell types chromogranin A-derived peptides might subserve a variety of different functions.

The effect of pancreatic mesenchyme on the differentiation of endocrine cells from gastric endoderm

Development ◽  
1987 ◽  
Vol 100 (4) ◽  
pp. 661-671 ◽  
Author(s):  
B. Kramer ◽  
A. Andrew ◽  
B.B. Rawdon ◽  
P. Becker
Keyword(s):  
Endocrine Cell ◽  
Endocrine Cells ◽  
Cell Types ◽  
The Other ◽  
Chick Embryos ◽  
Cell Type ◽  
Pancreatic Insulin ◽  
Somatostatin Cells ◽  
Regional Specificity ◽  
Gut Endocrine Cells

To determine whether mesenchyme plays a part in the differentiation of gut endocrine cells, proventricular endoderm from 4- to 5-day chick or quail embryos was associated with mesenchyme from the dorsal pancreatic bud of chick embryos of the same age. The combinations were grown on the chorioallantoic membranes of host chick embryos until they reached a total incubation age of 21 days. Proventricular or pancreatic endoderm of the appropriate age and species reassociated with its own mesenchyme provided the controls. Morphogenesis in the experimental grafts corresponded closely to that in proventricular controls, i.e. the pancreatic mesenchyme supported the development of proventricular glands from proventricular endoderm. Insulin, glucagon and somatostatin cells and cells with pancreatic polypeptide-like immunoreactivity differentiated in the pancreatic controls. The latter three endocrine cell types, together with neurotensin and bombesin/gastrin-releasing polypeptide (GRP) cells, developed in proventricular controls and experimental grafts. The proportions of the major types common to proventriculus and pancreas (somatostatin and glucagon cells) were in general similar when experimental grafts were compared with proventricular controls but different when experimental and pancreatic control grafts were compared. Hence pancreatic mesenchyme did not materially affect the proportions of these three cell types in experimental grafts, induced no specific pancreatic (insulin) cell type and allowed the differentiation of the characteristic proventricular endocrine cell types, neurotensin and bombesin/GRP cells. However, an important finding was a significant reduction in the proportion of bombesin/GRP cells, attributable in part to a decrease in their number and in part to an increase in the numbers of endocrine cells of the other types. This indicates that mesenchyme may well play a part in determining the regional specificity of populations of gut endocrine cells.

The distribution of endocrine cell progenitors in the gut of chick embryos

Development ◽  
1984 ◽  
Vol 82 (1) ◽  
pp. 131-145
Author(s):  
B. B. Rawdon ◽  
Beverley Kramer ◽  
Ann Andrew
Keyword(s):  
Gastrointestinal Tract ◽  
Progenitor Cells ◽  
Digestive Tract ◽  
Pancreatic Polypeptide ◽  
Endocrine Cell ◽  
Endocrine Cells ◽  
Chick Embryos ◽  
Intact Embryo ◽  
Pancreatic Endocrine Cells ◽  
Gut Endocrine Cells

The aim of this experiment was to find out whether or not, at early stages of development, progenitors of the various types of gut endocrine cells are localized to one or more specific regions of the gastrointestinal tract. Transverse strips of blastoderm two to four somites in length were excised between the levels of somites 5 and 27 in chick embryos at 5- to 24-somite stages and were cultured as chorioallantoic grafts. The distribution of endocrine cells in the grafts revealed confined localization of progenitor cells only in the case of insulinimmunoreactive cells. Theprogenitors of cells with somatostatin-, pancreatic polypeptide-, glucagon-, secretin-, gastrin/CCK-, motilin-, neurotensin- and serotonin-like immunoreactivity were distributed along the length of the presumptive gut at the time of explantation; indeed, in many cases they were more widespread than are their differentiated progeny in normal gut of the same age. This finding indicates that conditions in grafts must differ from those that operate in the intact embryo. Also it may explain the occurrence of ectopic gut or pancreatic endocrine cells in tumours of the digestive tract.

scholarly journals Regulation of Exocytosis by Protein Kinases and Ca2+ in Pancreatic Duct Epithelial Cells

2000 ◽  
Vol 116 (4) ◽  
pp. 507-520 ◽  
Author(s):  
Duk-Su Koh ◽  
Mark W. Moody ◽  
Toan D. Nguyen ◽  
Bertil Hille
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Pancreatic Duct ◽  
Endocrine Cells ◽  
Cell Types ◽  
Rapid Onset ◽  
Fusion Pore ◽  
Intracellular Camp ◽  
Downstream Effector ◽  
Adrenal Chromaffin

We asked if the mechanisms of exocytosis and its regulation in epithelial cells share features with those in excitable cells. Cultured dog pancreatic duct epithelial cells were loaded with an oxidizable neurotransmitter, dopamine or serotonin, and the subsequent release of these exogenous molecules during exocytosis was detected by carbon-fiber amperometry. Loaded cells displayed spontaneous exocytosis that may represent constitutive membrane transport. The quantal amperometric events induced by fusion of single vesicles had a rapid onset and decay, resembling those in adrenal chromaffin cells and serotonin-secreting leech neurons. Quantal events were frequently preceded by a “foot,” assumed to be leak of transmitters through a transient fusion pore, suggesting that those cell types share a common fusion mechanism. As in neurons and endocrine cells, exocytosis in the epithelial cells could be evoked by elevating cytoplasmic Ca2+ using ionomycin. Unlike in neurons, hyperosmotic solutions decreased exocytosis in the epithelial cells, and giant amperometric events composed of many concurrent quantal events were observed occasionally. Agents known to increase intracellular cAMP in the cells, such as forskolin, epinephrine, vasoactive intestinal peptide, or 8-Br-cAMP, increased the rate of exocytosis. The forskolin effect was inhibited by the Rp-isomer of cAMPS, a specific antagonist of protein kinase A, whereas the Sp-isomer, a specific agonist of PKA, evoked exocytosis. Thus, PKA is a downstream effector of cAMP. Finally, activation of protein kinase C by phorbol-12-myristate-13-acetate also increased exocytosis. The PMA effect was not mimicked by the inactive analogue, 4α-phorbol-12,13-didecanoate, and it was blocked by the PKC antagonist, bisindolylmaleimide I. Elevation of intracellular Ca2+ was not needed for the actions of forskolin or PMA. In summary, exocytosis in epithelial cells can be stimulated directly by Ca2+, PKA, or PKC, and is mediated by physical mechanisms similar to those in neurons and endocrine cells.

Co-expression of insulin and somatostatin genes in pancreatic endocrine cells selected for their high level of insulin gene transcription

1992 ◽  
Vol 101 (4) ◽  
pp. 795-799
Author(s):  
C. Saulnier-Michel ◽  
M. Fromont-Racine ◽  
R. Pictet
Keyword(s):  
Endocrine Cells ◽  
Selective Pressure ◽  
Cell Types ◽  
Insulin Gene ◽  
Regulatory Sequences ◽  
Endogenous Insulin ◽  
Pancreatic Endocrine Cells ◽  
Gene Regulatory ◽  
High Level ◽  
Two Populations

RW cells are pancreatic endocrine RIN cells that have been stably transfected with a chimeric gene that places the expression of the dominant selection gpt gene under the control of the insulin gene regulatory sequences. These RW cells were examined for hormone content using immunocytochemistry. This analysis shows that: first, there are cells that are negative for insulin although they were cultured under selective pressure. Second, there is a higher proportion of somatostatin-producing cells than in the parental RIN cells; these somatostatin cells form two populations: one of cells containing only somatostatin and, surprisingly, one made of cells containing both insulin and somatostatin. Thus: (1) expression of the transfected and endogenous insulin regulatory sequences is not regulated in a coordinate fashion; (2) the presence of both hormones in the same cell suggests that the regulation of the expression of insulin and somatostatin genes and the differentiation pathway of the two respective cell types may be closely related.

scholarly journals The SNAG Domain of Insm1 Regulates Pancreatic Endocrine Cell Differentiation and Represses Beta- to Delta-Cell Transdifferentiation

2021 ◽  
Author(s):  
Xuehua Liang ◽  
Hualin Duan ◽  
Yahui Mao ◽  
Ulrich Koestner ◽  
Yiqiu Wei ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Beta Cell ◽  
Endocrine Cell ◽  
Endocrine Cells ◽  
Cell Number ◽  
Pancreatic Endocrine Cell ◽  
Cell Transdifferentiation ◽  
Pancreatic Endocrine Cells ◽  
Delta Cell ◽  
Null Mutants

The allocation and specification of pancreatic endocrine lineages are tightly regulated by transcription factors. Disturbances in differentiation of these lineages contribute to the development of various metabolic diseases, including diabetes. The Insulinoma-associated protein 1 (<i>Insm1</i>), which encodes a protein containing one SNAG domain and five zinc fingers, plays essential roles in pancreatic endocrine cell differentiation and in mature beta-cell function. In the present study, we compared the differentiation of pancreatic endocrine cells between Insm1 null and Insm1 SNAG domain mutants (Insm1delSNAG) to explore the specific function of the SNAG domain of Insm1. We show that the delta-cell number is increased in Insm1delSNAG but not in Insm1 null mutants as compared to the control mice. We also show a less severe reduction of the beta-cell number in Insm1delSNAG as that in Insm1 null mutants. In addition, similar deficits are observed in alpha-, PP- and epsilon-cell in Insm1delSNAG and Insm1 null mutants. We further identified that the increased delta-cell number is due to beta- to delta-cell transdifferentiation. Mechanistically, the SNAG domain of Insm1 interacts with Lsd1, the demethylase of H3K4me1/2. Mutation in the SNAG domain of Insm1 results in impaired recruitment of Lsd1 and increased H3K4me1/2 levels at <i>H</i><i>hex</i> loci that are bound by Insm1, thereby promoting the transcriptional activity of the delta-cell-specific gene <i>Hhex</i>. Our study has identified a novel function of the SNAG domain of Insm1 in the regulation of pancreatic endocrine cells differentiation, particularly in the repression of beta- to delta-cell transdifferentiation.

scholarly journals Cellular distribution and amount of chromogranin A in bovine endocrine pancreas.

1988 ◽  
Vol 36 (5) ◽  
pp. 467-472 ◽  
Author(s):  
M Ehrhart ◽  
A Jörns ◽  
D Grube ◽  
M Gratzl
Keyword(s):  
Chromogranin A ◽  
Endocrine Cells ◽  
Endocrine Pancreas ◽  
Molar Ratio ◽  
Computer Assisted ◽  
Cellular Distribution ◽  
Tissue Extracts ◽  
Wet Weight ◽  
Pancreatic B Cells ◽  
Bovine Pancreas

We determined the cellular distribution and the amount of chromogranin A in endocrine cells of bovine pancreas using a polyclonal antibody against bovine adrenomedullary chromogranin A. The relative amounts of chromogranin A in the different cells of the endocrine pancreas were determined by computer-assisted analyses of the optical densities of the immunoreactivities in the stained sections. More than 80% of the immunoreactive chromogranin A was located in the pancreatic B-cells. In immunoblots of acid tissue extracts, only one chromogranin A band (MW 74 KD) was observed. Quantification of the immunoblots revealed that 3 micrograms of chromogranin A and 918 micrograms of insulin were present per gram pancreas (wet weight), equivalent to a molar ratio of 460 mumol chromogranin A per mol insulin.

scholarly journals The SNAG Domain of Insm1 Regulates Pancreatic Endocrine Cell Differentiation and Represses Beta- to Delta-Cell Transdifferentiation

2021 ◽  
Author(s):  
Xuehua Liang ◽  
Hualin Duan ◽  
Yahui Mao ◽  
Ulrich Koestner ◽  
Yiqiu Wei ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Beta Cell ◽  
Endocrine Cell ◽  
Endocrine Cells ◽  
Cell Number ◽  
Pancreatic Endocrine Cell ◽  
Cell Transdifferentiation ◽  
Pancreatic Endocrine Cells ◽  
Delta Cell ◽  
Null Mutants

The allocation and specification of pancreatic endocrine lineages are tightly regulated by transcription factors. Disturbances in differentiation of these lineages contribute to the development of various metabolic diseases, including diabetes. The Insulinoma-associated protein 1 (<i>Insm1</i>), which encodes a protein containing one SNAG domain and five zinc fingers, plays essential roles in pancreatic endocrine cell differentiation and in mature beta-cell function. In the present study, we compared the differentiation of pancreatic endocrine cells between Insm1 null and Insm1 SNAG domain mutants (Insm1delSNAG) to explore the specific function of the SNAG domain of Insm1. We show that the delta-cell number is increased in Insm1delSNAG but not in Insm1 null mutants as compared to the control mice. We also show a less severe reduction of the beta-cell number in Insm1delSNAG as that in Insm1 null mutants. In addition, similar deficits are observed in alpha-, PP- and epsilon-cell in Insm1delSNAG and Insm1 null mutants. We further identified that the increased delta-cell number is due to beta- to delta-cell transdifferentiation. Mechanistically, the SNAG domain of Insm1 interacts with Lsd1, the demethylase of H3K4me1/2. Mutation in the SNAG domain of Insm1 results in impaired recruitment of Lsd1 and increased H3K4me1/2 levels at <i>H</i><i>hex</i> loci that are bound by Insm1, thereby promoting the transcriptional activity of the delta-cell-specific gene <i>Hhex</i>. Our study has identified a novel function of the SNAG domain of Insm1 in the regulation of pancreatic endocrine cells differentiation, particularly in the repression of beta- to delta-cell transdifferentiation.

scholarly journals Postnatal development of intestinal endocrine cell populations in the water buffalo

1999 ◽  
Vol 195 (3) ◽  
pp. 439-446
Author(s):  
CARLA LUCINI ◽  
PAOLO DE GIROLAMO ◽  
LUIGI COPPOLA ◽  
GIUSEPPE PAINO ◽  
LUCIANA CASTALDO
Keyword(s):  
Postnatal Development ◽  
Endocrine Cell ◽  
Endocrine Cells ◽  
Water Buffalo ◽  
Regional Distribution ◽  
Gastric Inhibitory Polypeptide ◽  
Cell Types ◽  
Proximal Colon ◽  
Cell Populations ◽  
Adult Diet

The frequency and distribution of 11 endocrine cell populations were studied in the intestine of differently aged buffalo, grouped on the basis of diet: 2-d-olds (suckling), 5-mo-olds (weaning) and 5-y-olds (ruminant adult diet). The endocrine cell populations were identified immunocytochemically using antisera against 5-hydroxytryptamine (5-HT), somatostatin, gastrin, cholecystokinin (CCK), COOH-terminal octapeptide of gastrin/CCK, neurotensin, motilin, gastric inhibitory polypeptide (GIP), secretin, glucagon/glicentin (GLU/GLI) and polypeptide YY (PYY). In adult buffalos the regional distribution of endocrine cells is similar to that of other adult ruminants. During postnatal development, these cell types showed the following changes in their frequency and distribution: (1) 5-HT, neurotensin and gastrin/CCK immunoreactive cells (i.c.) showed a decrease in frequency with age; (2) somatostatin i.c. frequency remained stable with age; (3) motilin, GIP, secretin and CCK i.c. showed a slight increase in frequency with age; (4) GLU/GLI and PYY i.c. decreased in frequency with age in the small intestine, caecum and proximal colon and an increase in frequency in the rectum. It was hypothesised that the endocrine cell types, whose presence and localisation is substantially stable in all examined ages, probably contain substances that are strictly necessary for intestinal function. In contrast the hormones contained in the cell populations that decreased with age, are probably involved in physiological needs during the milk and weaning diet or play a role in intestinal growth.

scholarly journals Ontogeny of Cells Containing Insulin, Glucagon, Pancreatic Polypeptide Hormone and Somatostatin in the Bovine Pancreas

1985 ◽  
Vol 38 (3) ◽  
pp. 237 ◽  
Author(s):  
SN Reddy ◽  
RB Elliott
Keyword(s):  
Pancreatic Polypeptide ◽  
Endocrine Cells ◽  
Fetal Life ◽  
Cell Type ◽  
Polypeptide Hormone ◽  
Islet Metabolism ◽  
Pancreatic Endocrine Cells ◽  
Endocrine Cell Type ◽  
Bovine Pancreas ◽  
Histochemical Procedure

Antibodies to insulin, glucagon, pancreatic polypeptide hormone (pPj and somatostatin were used in the immunofluorescence histochemical procedure to study the ontogeny of pancreatic endocrine cells containing the four hormones in the bovine fetus of approximately 100 days gestation to term. Pancreatic sections from the bovine neonate and adult were also examined for the cellular distribution of the four hormones. Immunoreactive cells staining for insulin, glucagon, PP and somatostatin were present in the pancreas of all fetuses studied. Each endocrine cell type displayed a characteristic distribution within the developing pancreas and in the neonate and adult. The presence of the four islet hormones relatively early in bovine fetal life suggests that they may be important in intra- and extra-islet metabolism in the fetus.

scholarly journals β-Cell Deficit in Obese Type 2 Diabetes, a Minor Role of β-Cell Dedifferentiation and Degranulation

2016 ◽  
Vol 101 (2) ◽  
pp. 523-532 ◽  
Author(s):  
Alexandra E. Butler ◽  
Sangeeta Dhawan ◽  
Jonathan Hoang ◽  
Megan Cory ◽  
Kylie Zeng ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Endocrine Cell ◽  
Endocrine Cells ◽  
Cell Types ◽  
Minor Role ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
The Impact

Abstract Context: Type 2 diabetes is characterized by a β-cell deficit and a progressive defect in β-cell function. It has been proposed that the deficit in β-cells may be due to β-cell degranulation and transdifferentiation to other endocrine cell types. Objective: The objective of the study was to establish the potential impact of β-cell dedifferentiation and transdifferentiation on β-cell deficit in type 2 diabetes and to consider the alternative that cells with an incomplete identity may be newly forming rather than dedifferentiated. Design, Setting, and Participants: Pancreata obtained at autopsy were evaluated from 14 nondiabetic and 13 type 2 diabetic individuals, from four fetal cases, and from 10 neonatal cases. Results: Whereas there was a slight increase in islet endocrine cells expressing no hormone in type 2 diabetes (0.11 ± 0.03 cells/islet vs 0.03 ± 0.01 cells/islet, P &lt; .01), the impact on the β-cell deficit would be minimal. Furthermore, we established that the deficit in β-cells per islet cannot be accounted for by an increase in other endocrine cell types. The distribution of hormone negative endocrine cells in type 2 diabetes (most abundant in cells scattered in the exocrine pancreas) mirrors that in developing (embryo and neonatal) pancreas, implying that these may represent newly forming cells. Conclusions: Therefore, although we concur that in type 2 diabetes there are endocrine cells with altered cell identity, this process does not account for the deficit in β-cells in type 2 diabetes but may reflect, in part, attempted β-cell regeneration.

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