scholarly journals Pancreatic duodenal homeobox-1 and islet neogenesis-associated protein: a possible combined marker of activateable pancreatic cell precursors

2003 ◽  
Vol 177 (2) ◽  
pp. 249-259 ◽  
Author(s):  
JJ Gagliardino ◽  
H Del Zotto ◽  
L Massa ◽  
LE Flores ◽  
MI Borelli
Keyword(s):  
Beta Cell ◽  
Early Stage ◽  
Cell Mass ◽  
Protein A ◽  
Beta Cell Mass ◽  
Cell Subpopulation ◽  
Pancreatic Cell ◽  
Islet Neogenesis ◽  
Stage Of Development

The aim of this work was to study the possible relationship between pancreatic duodenal homeobox-1 (Pdx-1) and islet neogenesis-associated protein (INGAP) during induced islet neogenesis. Pregnant hamsters were fed with (S) and without (C) sucrose, and glycemia, insulin secretion in vitro, and pancreas immunomorphometric parameters were measured in their 7-day-old offspring. S offspring had significantly lower glycemic levels than C animals. Insulin release in response to increasing glucose concentrations in the incubation medium (2-16 mM glucose) did not increase in pancreata from either C or S offspring. However, pancreata from S offspring released more insulin than those from C animals. In S offspring, beta-cell mass, beta-cell replication rate and islet neogenesis increased significantly, with a simultaneous decrease in beta-cell apoptotic rate. INGAP- and Pdx-1-positive cell mass also increased in the islets and among acinar and duct cells. We found two subpopulations of Pdx-1 cells: INGAP-positive and INGAP-negative. Pdx-1/INGAP-positive cells did not stain with insulin, glucagon, somatostatin, pancreatic polypeptide, or neurogenin 3 antibodies. The increment of Pdx-1/INGAP-positive cells represented the major contribution to the Pdx-1 cell mass increase. Such increments varied among pancreas subsectors: ductal>insular>extrainsular. Our results suggested that INGAP participates in the regulation of islet neogenesis, and Pdx-1/INGAP-positive cells represent a new stem cell subpopulation at an early stage of development, highly activateable in neogenesis.

scholarly journals PET Imaging of GPR44 by Antagonist [11C]MK-7246 in Pigs

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 434
Author(s):  
Pierre Cheung ◽  
Bo Zhang ◽  
Emmi Puuvuori ◽  
Sergio Estrada ◽  
Mohammad A. Amin ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Emission Tomography ◽  
Pet Tracer ◽  
Positron Emission ◽  
In Vitro Cell Lines ◽  
Membrane Spanning ◽  
New Strategies

A validated imaging marker for beta-cell mass would improve understanding of diabetes etiology and enable new strategies in therapy development. We previously identified the membrane-spanning protein GPR44 as highly expressed and specific to the beta cells of the pancreas. The selective GPR44 antagonist MK-7246 was radiolabeled with carbon-11 and the resulting positron-emission tomography (PET) tracer [11C]MK-7246 was evaluated in a pig model and in vitro cell lines. The [11C]MK-7246 compound demonstrated mainly hepatobiliary excretion with a clearly defined pancreas, no spillover from adjacent tissues, and pancreatic binding similar in magnitude to the previously evaluated GPR44 radioligand [11C]AZ12204657. The binding could be blocked by preadministration of nonradioactive MK-7246, indicating a receptor-binding mechanism. [11C]MK-7246 showed strong potential as a PET ligand candidate for visualization of beta-cell mass (BCM) and clinical translation of this methodology is ongoing.

Differentiation and Expansion of Beta Cell Mass in Porcine Neonatal Pancreatic Cell Clusters Transplanted into Nude Mice

1999 ◽  
Vol 8 (6) ◽  
pp. 673-689 ◽  
Author(s):  
Kun-Ho Yoon ◽  
Robert R. Quickel ◽  
Krystyna Tatarkiewicz ◽  
Thomas R. Ulrich ◽  
Jennifer Hollister-Lock ◽  
...  
Keyword(s):  
Beta Cell ◽  
Nude Mice ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Pancreatic Cell ◽  
Cell Clusters

In vivo and in vitro characterization of [18F]-FE-(+)-DTBZ as a tracer for beta-cell mass

2010 ◽  
Vol 37 (3) ◽  
pp. 357-363 ◽  
Author(s):  
Olof Eriksson ◽  
Mahabuba Jahan ◽  
Peter Johnström ◽  
Olle Korsgren ◽  
Anders Sundin ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
In Vitro Characterization

scholarly journals The Bile Acid TUDCA Improves Beta-Cell Mass and Reduces Insulin Degradation in Mice With Early-Stage of Type-1 Diabetes

2019 ◽  
Vol 10 ◽  
Author(s):  
Gabriela Alves Bronczek ◽  
Jean Franciesco Vettorazzi ◽  
Gabriela Moreira Soares ◽  
Mirian Ayumi Kurauti ◽  
Cristiane Santos ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Bile Acid ◽  
Beta Cell ◽  
Early Stage ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Insulin Degradation

scholarly journals Possible relationship between changes in islet neogenesis and islet neogenesis-associated protein-positive cell mass induced by sucrose administration to normal hamsters

2000 ◽  
Vol 165 (3) ◽  
pp. 725-733 ◽  
Author(s):  
H Del Zotto ◽  
L Massa ◽  
R Rafaeloff ◽  
GL Pittenger ◽  
A Vinik ◽  
...  
Keyword(s):  
Beta Cell ◽  
Endocrine Pancreas ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Serum Glucose ◽  
Islet Neogenesis ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Ductal Cells ◽  
Islet Volume

The possible relationship between changes in islet cell mass and in islet neogenesis-associated protein (INGAP)-cell mass induced by sucrose administration to normal hamsters was investigated. Normal hamsters were given sucrose (10% in drinking water) for 5 (S8) or 21 (S24) weeks and compared with control (C) fed hamsters. Serum glucose and insulin levels were measured and quantitative immunocytochemistry of the endocrine pancreas was performed. Serum glucose levels were comparable among the groups, while insulin levels were higher in S hamsters. There was a significant increase in beta-cell mass (P<0.02) and in beta-cell 5-bromo-2'-deoxyuridine index (P<0.01), and a significant decrease in islet volume (P<0.01) only in S8 vs C8 hamsters. Cytokeratin (CK)-labelled cells were detected only in S8 hamsters. INGAP-positive cell mass was significantly larger only in S8 vs C8 hamsters. Endocrine INGAP-positive cells were located at the islet periphery ( approximately 96%), spread within the exocrine pancreas ( approximately 3%), and in ductal cells (<1%) in all groups. INGAP positivity and glucagon co-localization varied according to topographic location and type of treatment. In C8 hamsters, 49.1+/-6. 9% cells were INGAP- and glucagon-positive in the islets, while this percentage decreased by almost half in endocrine extra-insular and ductal cells. In S8 animals, co-expression increased in endocrine extra-insular cells to 36.3+/-9.5%, with similar figures in the islets, decreasing to 19.7+/-6.9% in ductal cells. INGAP-positive cells located at the islet periphery also co-expressed CK. In conclusion, a significant increase of INGAP-positive cell mass was only observed at 8 weeks when neogenesis was present, suggesting that this peptide might participate in the control of islet neogenesis. Thus, INGAP could be a potentially useful tool to treat conditions in which there is a decrease in beta-cell mass.

scholarly journals Insulin-positive ductal cells do not migrate into preexisting islets during pregnancy

2021 ◽  
Author(s):  
Qun Liu ◽  
Yinan Jiang ◽  
Lingyan Zhu ◽  
Jieqi Qian ◽  
Chaoban Wang ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Gene Expression Omnibus ◽  
Glucose Response ◽  
Ductal Cells ◽  
Duct Cells ◽  
And Migration

AbstractThe adult pancreatic ductal system was suggested to harbor facultative beta-cell progenitors similar to the embryonic pancreas, and the appearance of insulin-positive duct cells has been used as evidence for natural duct-to-beta-cell reprogramming. Nevertheless, the phenotype and fate of these insulin-positive cells in ducts have not been determined. Here, we used a cell-tagging dye, CFDA-SE, to permanently label pancreatic duct cells through an intraductal infusion technique. Representing a time when significant increases in beta-cell mass occur, pregnancy was later induced in these CFDA-SE-treated mice to assess the phenotype and fate of the insulin-positive cells in ducts. We found that a small portion of CFDA-SE-labeled duct cells became insulin-positive, but they were not fully functional beta-cells based on the in vitro glucose response and the expression levels of key beta-cell genes. Moreover, these insulin-positive cells in ducts expressed significantly lower levels of genes associated with extracellular matrix degradation and cell migration, which may thus prevent their budding and migration into preexisting islets. A similar conclusion was reached through analysis of the Gene Expression Omnibus database for both mice and humans. Together, our data suggest that the contribution of duct cells to normal beta-cells in adult islets is minimal at best.

scholarly journals Exendin-4 Promotes Beta Cell Proliferation via PI3k/Akt Signalling Pathway

2015 ◽  
Vol 35 (6) ◽  
pp. 2223-2232 ◽  
Author(s):  
Chaoxun Wang ◽  
Xiaopan Chen ◽  
Xiaoying Ding ◽  
Yanju He ◽  
Chengying Gu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Beta Cell ◽  
Molecular Mechanisms ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Cell Number ◽  
Beta Cell Proliferation ◽  
Proliferation In Vitro

Background/Aims: Prevention of diabetes requires maintenance of a functional beta-cell mass, the postnatal growth of which depends on beta cell proliferation. Past studies have shown evidence of an effect of an incretin analogue, Exendin-4, in promoting beta cell proliferation, whereas the underlying molecular mechanisms are not completely understood. Methods: Here we studied the effects of Exendin-4 on beta cell proliferation in vitro and in vivo through analysing BrdU-incorporated beta cells. We also analysed the effects of Exendin-4 on beta cell mass in vivo, and on beta cell number in vitro. Then, we applied specific inhibitors of different signalling pathways and analysed their effects on Exendin-4-induced beta cell proliferation. Results: Exendin-4 increased beta cell proliferation in vitro and in vivo, resulting in significant increases in beta cell mass and beta cell number, respectively. Inhibition of PI3K/Akt signalling, but not inhibition of either ERK/MAPK pathway, or JNK pathway, significantly abolished the effects of Exendin-4 in promoting beta cell proliferation. Conclusion: Exendin-4 promotes beta cell proliferation via PI3k/Akt signaling pathway.

scholarly journals A Pentadecapeptide Fragment of Islet Neogenesis-Associated Protein Increases Beta-Cell Mass and Reverses Diabetes in C57BL/6J Mice

2004 ◽  
Vol 240 (5) ◽  
pp. 875-884 ◽  
Author(s):  
Lawrence Rosenberg ◽  
Mark Lipsett ◽  
Ji-Won Yoon ◽  
Marc Prentki ◽  
Rennian Wang ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Islet Neogenesis

Investigation on the Protective Effect of Canagliflozin on Pancreatic Beta-Cell Mass Using SPECT/CT Imaging with 111In-Labeled Exendin-4

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2124-P
Author(s):  
KEITA HAMAMATSU ◽  
HIROYUKI FUJIMOTO ◽  
NAOTAKA FUJITA ◽  
TAKAAKI MURAKAMI ◽  
MASAHARU SHIOTANI ◽  
...  
Keyword(s):  
Beta Cell ◽  
Protective Effect ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Ct Imaging ◽  
Pancreatic Beta Cell Mass
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