scholarly journals Induction of pancreatic acinar cell proliferation by thyroid hormone

2005 ◽  
Vol 185 (3) ◽  
pp. 393-399 ◽  
Author(s):  
G M Ledda-Columbano ◽  
A Perra ◽  
M Pibiri ◽  
F Molotzu ◽  
A Columbano
Keyword(s):  
Cell Proliferation ◽  
Thyroid Hormone ◽  
Dna Synthesis ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Labeling Index ◽  
Metabolic Effects ◽  
Brdu Incorporation ◽  
Pancreatic Cell

Thyroid hormone is known to elicit diverse cellular and metabolic effects in various organs, including mitogenesis in the rat liver. In the present study, experiments were carried out to determine whether thyroid hormone is able to stimulate cell proliferation in another quiescent organ such as the pancreas. 3,5,3′-l-tri-iodothyronine (T3) added to the diet at a concentration of 4 mg/kg caused a striking increase in nuclear bromodeoxyuridine (BrdU) incorporation of rat acinar cells 7 days after treatment (the labeling index was 46.7% in T3-treated rats vs 7.1% in controls). BrdU incorporation was limited to the acinar cells, with duct cells and islet cells being essentially negative. The increase in DNA synthesis was accompanied by the presence of several mitotic figures. Histological examination of the pancreas did not exhibit any sign of T3-induced toxicity. Determination of the apoptotic index, measurement of the serum levels of α-amylase and lipase, and glycemia determination did not show any increase over control values, suggesting that the enhanced proliferation of acinar cells was a direct effect induced by T3 and not a regenerative response consequent to acinar or β-cell injury. Additional experiments showed that DNA synthesis was induced as early as 2 days after T3 treatment (the labeling index was 9.4 vs 1.9% in controls) and was associated with increased protein levels of cyclin D1, cyclin A and proliferating cell nuclear antigen, with no substantial differences in the expression of the cyclin-dependent kinase inhibitor p27. The mitogenic effect of T3 on the pancreas was not limited to the rat, since extensive acinar cell proliferation was also observed in the pancreas of mice treated with T3 for 1 week (the labeling index was 28% in T3-treated mice vs 1.8% in controls). Treatment with three other ligands of nuclear receptors, ciprofibrate, all-trans retinoic acid and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, induced little or no pancreatic cell proliferation. These results demonstrated that T3 is a powerful inducer of cell proliferation in the pancreas and suggested that pancreatic acinar cell proliferation by selected agents may have potential for therapeutic use.

Short-term effects of feeding raw soya flour on pancreatic cell turnover in the rat

1984 ◽  
Vol 247 (6) ◽  
pp. G667-G673
Author(s):  
P. S. Oates ◽  
R. G. Morgan
Keyword(s):  
Dna Synthesis ◽  
Cell Damage ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Soya Flour ◽  
Cell Turnover ◽  
Tissue Necrosis ◽  
Short Term ◽  
Pancreatic Cell ◽  
Duct Cells

Pancreatic acinar cell turnover was studied after a 48-h fast and in rats fed raw soya flour (RSF) for up to 28 days. Feeding RSF for 2 days resulted in a significant increase in pancreatic weight and RNA content while protein was increased by the 4th day compared with rats fasted for 48 h. RSF also resulted in a significant increase in RNA by the 4th day and weight and protein by the 7th day compared with rats fed heated soya flour (HSF). This pancreatic hypertrophy was maintained for the rest of the study period. Two days after starting RSF, pancreatic DNA synthesis, measured bythe rate of incorporation of [3H]thymidine into pancreatic DNA, had increased sixfold compared with that in animals fedHSF but returned to control values again by the 4th day on the diet. Autoradiography showed that this increase in DNA synthesis occurred in both acinar and duct cells, with turnover in acinar cells preceding that in duct cells. A second moregradual rise in DNA synthesis was seen from the 7th to 28th day. This peak in DNA synthesis was associated with an increased total pancreatic DNA content and occurred predominately in duct cells with a smaller contribution from acinar cells. Histological studies of the pancreas during the 1st wk showed cell damage and tissue necrosis, possibly due to exposure to high levels of cholecystokinin released by RSF. The first peak in DNA synthesis may be a regenerative response to this damage. The second more delayed peak appears to be hyperplasia in response to a trophic stimulus, again possibly mediated by cholecystokinin.

scholarly journals SEC23B is required for pancreatic acinar cell function in adult mice

2017 ◽  
Vol 28 (15) ◽  
pp. 2146-2154 ◽  
Author(s):  
Rami Khoriaty ◽  
Nancy Vogel ◽  
Mark J. Hoenerhoff ◽  
M. Dolors Sans ◽  
Guojing Zhu ◽  
...  
Keyword(s):  
Acinar Cell ◽  
Cell Function ◽  
Acinar Cells ◽  
Cell Loss ◽  
Normal Function ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Total Protein Content ◽  
Pancreatic Cell ◽  
Adult Mice

Mice with germline absence of SEC23B die perinatally, exhibiting massive pancreatic degeneration. We generated mice with tamoxifen-inducible, pancreatic acinar cell–specific Sec23b deletion. Inactivation of Sec23b exclusively in the pancreatic acinar cells of adult mice results in decreased overall pancreatic weights from pancreatic cell loss (decreased pancreatic DNA, RNA, and total protein content), as well as degeneration of exocrine cells, decreased zymogen granules, and alterations in the endoplasmic reticulum (ER), ranging from vesicular ER to markedly expanded cisternae with accumulation of moderate-density content or intracisternal granules. Acinar Sec23b deletion results in induction of ER stress and increased apoptosis in the pancreas, potentially explaining the loss of pancreatic cells and decreased pancreatic weight. These findings demonstrate that SEC23B is required for normal function of pancreatic acinar cells in adult mice.

scholarly journals c-Jun/AP-1 is required for CCK-induced pancreatic acinar cell dedifferentiation and DNA synthesis in vitro

2012 ◽  
Vol 302 (12) ◽  
pp. G1381-G1396 ◽  
Author(s):  
Lili Guo ◽  
Maria Dolors Sans ◽  
Yanan Hou ◽  
Stephen A. Ernst ◽  
John A. Williams
Keyword(s):  
Dna Synthesis ◽  
Cyclin D1 ◽  
Signaling Pathways ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Dominant Negative ◽  
Cell Dedifferentiation ◽  
Cell Markers

Endogenous CCK plays an important role in pancreatic regeneration after pancreatitis. We used primary culture of mouse pancreatic acinar cells to evaluate the effect of CCK on acinar cell morphology and gene expression and to determine signaling pathways required for proliferation of acinar cells in vitro. Over 4 days in culture, cells grew out from acini and formed patches of monolayer, which displayed a reduced expression of acinar cell markers including digestive enzymes and Mist1 and an increased expression of ductal and embryonic markers, including cytokeratin 7, β-catenin, E-cadherin, pdx-1, and nestin. There was no appearance of stellate cell markers. CCK enhanced cellular spreading, DNA synthesis, and cyclin D1 expression. When signaling pathways were evaluated, CCK stimulation increased c-Jun expression, JNK and ERK activity, and AP-1 activation. Chemical inhibitors of JNK and ERK pathways, dominant-negative JNK and c-Jun, and c-Jun shRNA significantly inhibited CCK-induced DNA synthesis, CCK-induced AP-1 activation, and cyclin D1 expression. Furthermore, dominant-negative c-Jun reduced the increased expression of β-catenin and the decreased expression of amylase during culture. These results show that MAPK/c-Jun/AP-1 pathway plays an important role in pancreatic acinar cell dedifferentiation and proliferation in culture. Monolayer culture can serve as a model to study acinar cell proliferation similar to regeneration after pancreatitis in vivo.

Stimulation of pancreatic acinar cell growth by CCK, epidermal growth factor, and insulin in vitro

1986 ◽  
Vol 251 (4) ◽  
pp. G487-G494 ◽  
Author(s):  
C. D. Logsdon
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Intracellular Camp ◽  
Ionophore A23187 ◽  
Epidermal Growth

Effects of regulatory molecules on growth of mouse pancreatic acinar cells in culture were examined. The cholecystokinin (CCK) analogue caerulein and cholecystokinin octapeptide (CCK-8) each led to threefold increases in incorporation of [3H]thymidine into DNA. Gastrin, which interacts weakly with the CCK receptor, stimulated DNA synthesis, but only at much higher concentrations. In contrast, other secretagogues that utilize Ca2+ as an intracellular messenger, including carbachol, bombesin, substance P, and the ionophore A23187, did not induce trophic responses. Factors that affect intracellular cAMP concentration, such as secretin, somatostatin, VIP, DBcAMP, and forskolin, did not increase DNA synthesis in cultured pancreatic cells. Insulin and epidermal growth factor induced two- and threefold increases in [3H] thymidine incorporation into DNA, respectively. The effects of insulin were mediated via insulin-like growth factor I receptors. Steroid hormones had little effect on pancreatic acinar cell DNA synthesis. The stimulatory effects of CCK, insulin, and EGF were additive. The combination of caerulein, EGF, and insulin in a hormonally defined medium led to a tenfold increase in the incorporation of [3H]thymidine into DNA. These data indicate that CCK, EGF, and insulin directly increase DNA synthesis in pancreatic acinar cells.

scholarly journals Age-dependent reduction of the PI3K regulatory subunit p85α suppresses pancreatic acinar cell proliferation

Aging Cell ◽  
2012 ◽  
Vol 11 (2) ◽  
pp. 305-314 ◽  
Author(s):  
Hitoshi Takahashi ◽  
Daiki Okamura ◽  
Marlene E. Starr ◽  
Hiroshi Saito ◽  
B. Mark Evers
Keyword(s):  
Cell Proliferation ◽  
Acinar Cell ◽  
Pancreatic Acinar Cell ◽  
Regulatory Subunit ◽  
Age Dependent

Crambene induces pancreatic acinar cell apoptosis via the activation of mitochondrial pathway

2006 ◽  
Vol 291 (1) ◽  
pp. G95-G101 ◽  
Author(s):  
Yang Cao ◽  
Sharmila Adhikari ◽  
Abel Damien Ang ◽  
Marie Véronique Clément ◽  
Matthew Wallig ◽  
...  
Keyword(s):  
Acinar Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Fas Ligand ◽  
Annexin V ◽  
Acinar Cells ◽  
Mitochondrial Pathway ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Pancreatic Acini

We investigated the apoptotic pathway activated by crambene (1-cyano-2-hydroxy-3-butene), a plant nitrile, on pancreatic acinar cells. As evidenced by annexin V-FITC staining, crambene treatment for 3 h induced the apoptosis but not necrosis of pancreatic acini. Caspase-3, -8, and -9 activities in acini treated with crambene were significantly higher than in untreated acini. Treatment with caspase-3, -8, and -9 inhibitors inhibited annexin V staining, as well as caspase-3 activity, pointing to an important role of these caspases in crambene-induced acinar cell apoptosis. The mitochondrial membrane potential was collapsed, and cytochrome c was released from the mitochondria in crambene-treated acini. Neither TNF-α nor Fas ligand levels were changed in pancreatic acinar cells after crambene treatment. These results provide evidence for the induction of pancreatic acinar cell apoptosis in vitro by crambene and suggest the involvement of mitochondrial pathway in pancreatic acinar cell apoptosis.

Effects of pancreatic acinar cell surface antibodies and complement on isolated rat acinar cells in vitro

1988 ◽  
Vol 55 (1) ◽  
Author(s):  
H. -U. Schulz ◽  
G. Letko ◽  
H. -J. Hass ◽  
H. Spormann ◽  
P. Kemnitz ◽  
...  
Keyword(s):  
Cell Surface ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Surface Antibodies ◽  
Isolated Rat

Multiple isoforms of the ryanodine receptor are expressed in rat pancreatic acinar cells

2000 ◽  
Vol 351 (1) ◽  
pp. 265-271 ◽  
Author(s):  
Timothy J. FITZSIMMONS ◽  
Ilya GUKOVSKY ◽  
James A. McROBERTS ◽  
Edward RODRIGUEZ ◽  
F. Anthony LAI ◽  
...  
Keyword(s):  
Western Blot ◽  
Ryanodine Receptor ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Protein Band ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Rt Pcr ◽  
Pancreatic Acini ◽  
Cell Functions

Regulation of cytosolic Ca2+ is important for a variety of cell functions. The ryanodine receptor (RyR) is a Ca2+ channel that conducts Ca2+ from internal pools to the cytoplasm. To demonstrate the presence of the RyR in the pancreatic acinar cell, we performed reverse transcriptase (RT)-PCR, Western blot, immunocytochemistry and microscopic Ca2+-release measurements on these cells. RT-PCR showed the presence of mRNA for RyR isoforms 1, 2 and 3 in both rat pancreas and dispersed pancreatic acini. Furthermore, mRNA expression for RyR isoforms 1 and 2 was demonstrated by RT-PCR in individual pancreatic acinar cells selected under the microscope. Western-blot analysis of acinar cell immunoprecipitates, using antibodies against RyR1 and RyR2, showed a high-molecular-mass (> 250kDa) protein band that was much less intense when immunoprecipitated in the presence of RyR peptide. Functionally, permeablized acinar cells stimulated with the RyR activator, palmitoyl-CoA, released Ca2+ from both basolateral and apical regions. These data show that pancreatic acinar cells express multiple isoforms of the RyR and that there are functional receptors throughout the cell.

S1686 Activated Protein C Induces Pancreatic Acinar Cell Proliferation Through the PI3K/AKT Pathway

2010 ◽  
Vol 138 (5) ◽  
pp. S-253
Author(s):  
Hitoshi Takahashi ◽  
Mark Evers ◽  
Hiroshi Saito
Keyword(s):  
Cell Proliferation ◽  
Acinar Cell ◽  
Protein C ◽  
Activated Protein C ◽  
Pancreatic Acinar Cell ◽  
Akt Pathway

scholarly journals Insulin Stimulates Goose Liver Cell Growth by Activating PI3K-AKT-mTOR Signal Pathway

2016 ◽  
Vol 38 (2) ◽  
pp. 558-570 ◽  
Author(s):  
Chunchun Han ◽  
Shouhai Wei ◽  
Qi Song ◽  
Fang He ◽  
Xiangping Xiong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Synthesis ◽  
Protein Content ◽  
Mrna Level ◽  
Signal Pathway ◽  
Mtor Pathway ◽  
Brdu Incorporation ◽  
Primary Hepatocytes

Background/Aims: Recent studies have suggested a crucial role for PI3K-Akt-mTOR pathway in regulating cell proliferation, so we hypothesize that insulin acts goose hepatocellular growth by PI3K-Akt-mTOR signal pathway. Because the physiological status of liver cells in vitro is different from that in vivo, a simplified cell model in vitro was established. Methods: Goose primary hepatocytes were isolated and incubated in either no addition as a control or insulin or PI3K-Akt-mTOR pathway inhibitors or co-treatment with glucose and PI3K-Akt-mTOR pathway inhibitors; Then, cell DNA synthesis and cell cycle analysis were detected by BrdU-incorporation Assay and Flow cytometric analysis; the mRNA expression and protein expression of factors involved in the cell cycle were determined by Real-Time RT-PCR, ELISA, and western blot. Results: Here we first showed that insulin evidently increased the cell DNA synthesis, the mRNA level and protein content of factors involved in the cell proliferation of goose primary hepatocytes. Meanwhile, insulin evidently increased the mRNA level and protein content of factors involved in PI3K-Akt-mTOR pathway. However, the up-regulation of insulin on cell proliferation was decreased significantly by the inhibitors of PBK-Akt-mTOR pathway, LY294002, rapamycin or NVP-BEZ235. Conclusion: These findings suggest that PI3K-Akt-mTOR pathway plays an essential role in insulin-regulated cell proliferation of goose hepatocyte.

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