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At least 19 recordsLinked to original sources
PubMed1987

Functional differentiation of alveolar type II epithelial cells in vitro: effects of cell shape, cell-matrix interactions and cell-cell interactions.

Alveolar type II epithelial cells rapidly lose characteristics of differentiated function when cultured on plastic dishes. We have attempted to circumvent this problem by culturing type II cells under conditions that might better reproduce their environment in vivo. Cell-matrix interactions were studied by culturing isolated adult rat type II cells on Engelbreth-Holm-Swarm (EHS) tumor basement membrane. Aggregates of type II cells formed on the surface of the matrix during 4 days in culture. Microscopic examination of these aggregates revealed cuboidal cells that retained more characteristics of differentiated type II cells than did cells cultured on plastic. Type II cells cultured on EHS matrix incorporated a higher percentage of acetate into phosphatidylcholine (PC) than did cells on plastic, and a higher percentage of this PC was saturated. Phosphatidylglycerol (PG) synthesis by these cells was no different from that seen in cells on plastic. The effects of cell-cell interactions and cell shape were evaluated by culturing type II cells on feeder layers that in turn were grown on collagen gels. The feeder layer cells included fetal rat lung fibroblasts, adult rat lung fibroblasts, fetal rat skin fibroblasts, bovine aortic endothelial cells, and rat mammary tumor epithelial cells. One-half of the gels remained attached to the culture dish and one-half of the gels were detached after 24 h and allowed to float free in the medium. Type II cells grown in association with any of the attached feeder layers became flattened and lost their differentiated phenotype. These cells incorporated no greater percentage of acetate into PC than did cells on plastic. Saturated PC synthesis was modestly increased. PG synthesis declined in parallel with that seen in cells cultured on plastic. Type II cells cultured on feeder layers that were detached assumed their native cuboidal shape and also exhibited many morphological characteristics of differentiated function. These cells incorporated a significantly greater percentage of acetate into PC compared to cells on either plastic or attached feeder layers. Saturated PC synthesis also increased markedly. These cells, however, incorporated no greater percentage of acetate into PG than did cells on plastic or attached feeder layers. These data suggest an important role for cell shape and cell-matrix interactions and maintenance of type II cell differentiation. The effects of cell-cell interactions, while beneficial, appear to be non-specific.

Animals↗
PubMed1988

Comparison of the facilitative roles of insulin and insulin-like growth factor I in the functional differentiation of granulosa cells: in vitro studies with the porcine model.

The facilitative effects of insulin and IGF-I were compared in vitro with regard to induction of differentiated functions of porcine granulosa cells. The monolayers were maintained under serum-free conditions in the absence or presence of porcine FSH (20 micrograms/l), with or without graded doses of insulin or IGF-I. Concurrent treatment with IGF-I and FSH produced morphological differentiation and augmented LH/hCG receptor binding together with an enhancement in progesterone and estradiol secretion relative to treatment with FSH alone. IGF-I alone was incapable of exhibiting these effects. Insulin synergized with FSH to facilitate the granulosa cell functions except estradiol secretion. Maximal effective dose of IGF-I was 100 micrograms/l which is within the physiological concentration in vivo, whereas that of insulin was 1.0 mg/l, which is 1000-fold higher than the physiological level. Although the maximal effective doses of IGF-I and insulin produced a comparable increment in progesterone secretion and LH/hCG receptor induction, combined treatment with IGF-I and insulin did not prove additive. [125I]IGF-I binding revealed that specific IGF-I receptors with two classes of binding sites are present on porcine granulosa cells. No distinct differences were detected between IGF-I receptors of granulosa cells from small, medium and large follicles. Insulin was approximately 100-fold less active than IGF-I in competing for [125I]IGF-I binding. These findings suggest that porcine granulosa cells possess specific IGF-I binding sites which may mediate the cytodifferentiative actions of insulin-like peptides. Since IGF-I is more potent than insulin in amplifying the actions of FSH and maximally exerts the cytodifferentiative effects at the physiological concentration, it is likely that IGF-I plays the more important role in granulosa cell differentiation in synergy with FSH.

Animals↗
PubMed1989

Cellular senescence involves stochastic processes causing loss of expression of differentiated function genes: transfection with SV40 as a means for dissociating effects of senescence on growth and on differentiated function gene expression.

In the accompanying work we demonstrated that the decline in expression of steroid 17 alpha-hydroxylase in mass cultures and clones of adrenocortical cells is the result of a stochastic switching process which yields mixtures of expressing and nonexpressing cells. There is an apparent positive correlation between the replicative potential of adrenocortical cell cultures and the number of cells in the culture that can express 17 alpha-hydroxylase. We investigated this by extending the cells' replicative potential by transfecting them with cloned SV40 virus. Cells from a senescent subclone, with very limited remaining replicative potential, were transfected. The cell population showed a progressive increase in growth rate and gave rise to a line of cells that expressed T antigen and which was apparently immortalized. Induction of mRNA for 17 alpha-hydroxylase by cyclic AMP was absent in this line of cells, as it was in the senescent cells prior to transfection. The cells remained responsive to gene induction by cyclic AMP as evidenced by increases in mRNA and activity for cholesterol side-chain cleavage. The absence of 17 alpha-hydroxylase expression in this line was not the result of interference by SV40 T antigen. When early passage cells were transfected with pSV3neo, which contains the early region of SV40 and neo, and were selected with G418, SV40 T antigen-expressing lines were derived which showed high levels of expression of 17 alpha-hydroxylase after induction with cyclic AMP. These cells maintained high levels of expression of 17 alpha-hydroxylase through four successive recloning events, over a period of replication much longer than that achievable by nontransfected cells. Thus, transfection by SV40 can be used to dissociate effects of senescence on growth and differentiated gene expression. T antigen expression selectively affects growth, but preserves the state of expression of a differentiated function gene as it was prior to transfection.

Adrenal Cortex↗
PubMed1987

Induction of morphological and functional differentiation of human myeloid leukemia cells (HL-60 and LK) by a benzoic acid derivative of retinoic acid.

In previous studies we have shown that the synthetic retinoid (E)-4[2-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl-1- propenyl]benzoic acid (TTNPB) stimulates the growth of myeloid progenitors from normal and myelodysplastic patients. In the present study we compared TTNPB with 13-cis-retinoic acid (RA) in its potential to inhibit cell growth and to induce morphological differentiation and functional activity in two cell lines established in vitro from either acute promyelocytic (HL-60) or acute myelomonocytic (LK) patients. Both agents, 10(-6) M, were found to effectively inhibit cell growth and cause a significant decrease in number of immature granulocytes in both cell lines. However, while in HL-60 cells this decrease was associated with a concomitant increase in fully mature granulocytes (neutrophil-like cells) the maturation of LK cells was blocked at the metamyelocyte stage. Study of the functional activity of the induced cells revealed that the rate of superoxide (O-2) production, as assayed by superoxide dismutase-inhibitable ferricytochrome c reduction, was faster in RA treated HL-60 cells than in TTNPB treated cells (0.41 vs. 0.25 nmol. O2-/10(6) cells/60 min). Superoxide production by LK cells treated by either TTNPB or RA was negligible. The percentage of O2(-)-producing cells was determined cytochemically by their ability to reduce the dye nitroblue tetrazolium (NBT). The results showed that production of O2-by LK cells exposed to TTNPB or RA was negligible by this method as well. A higher percentage of HL-60 cells reduced NBT following incubation with RA than with TTNPB (93 +/- 4% vs 26 +/- 2%), but neither of the two retinoids affected the ability of LK cells to reduce NBT. TTNPB thus proved less effective than RA in inducing morphological and functional differentiation in HL-60 cells, whereas in LK cells both agents inhibited cell growth but induced only partial cell differentiation.

Benzoates↗
PubMed1987

Cell contact but not junctional communication (dye coupling) with biliary epithelial cells is required for hepatocytes to maintain differentiated functions.

Specific differentiated gene expression and the morphology of adult rat hepatocytes can be maintained for as long as 8 weeks in vitro only when they are cultured in the presence of biliary epithelial cells; when primary hepatocytes are cultured alone, they lose these functions within 2 to 3 days. We obtained evidence suggesting that contact between hepatocytes and biliary epithelial cells is necessary for maintaining hepatocyte functions. We examined whether junctional communication between and among hepatocytes and biliary epithelial cells is required for long-term maintenance of hepatocyte functions, using a dye-transfer method, in three co-cultures: (1) hepatocytes and biliary epithelial cells prepared from Sprague-Dawley rats; (2) hepatocytes from Sprague-Dawley rats and epithelial cells of the IAR 20 line, originally established from BDVI rats; and (3) hepatocytes from BDVI rats and IAR 20 epithelial cells. The established epithelial cell line (IAR 20) and early-passage cultures of biliary epithelial cells maintained hepatocyte-specific functions in culture for 40 and 70 days, respectively, but the latter induced more stable maintenance of albumin secretion. Hepatocytes cultured alone lost their characteristic morphology within 5 to 8 days, and almost no dye transfer was observed. In co-cultures, the capacity of biliary epithelial cells to communicate among themselves remained relatively high throughout the culture period, whereas hepatocytes showed almost no junctional communication at an early phase of culture and first began to communicate after 2 weeks, communication capacity increasing for at least the next 10 days of culture. The most notable finding was that there was no dye transfer between hepatocytes and biliary epithelial cells in any co-culture system. These results suggest that the maintenance of hepatocyte-specific functions requires intercellular contact but probably not gap-junctional communication between hepatocytes and biliary epithelial cells. This system is useful for studying heterotypic cell-cell interactions and the control of gene expression.

Albumins↗
PubMed1987

Functional differentiation of virgin mouse mammary epithelium in explant culture is dependent upon extracellular proline.

Depletion of proline from insulin, hydrocortisone, and prolactin-containing medium prior to incubating virgin mouse mammary explants prevents both DNA synthesis and functional differentiation in the mammary epithelial cells; however, DNA synthesis in the mammary stroma and total incorporation of radioactive amino acids into total protein appears to continue without hindrance. Removal of glycine instead of proline had no deleterious effect on either DNA replication in the hormone-stimulated epithelium or in its functional differentiation. Functional differentiation was determined by the induction of casein and alpha-lactalbumin synthesis in the insulin, hydrocortisone, and prolactin (IFPrl)-treated explant cultures. As a control, the induction of mouse mammary tumor virus (MMTV) gene expression, a corticosteroid-regulated function, was also measured. Neither the absence of proline or glycine prevented the glucocorticoid stimulation of MMTV gene expression. In contrast to mammary tissue from virgin mice, explants from nonpregnant primiparous mice responded fully to IFPrl stimulation with respect to DNA, casein, and alpha-lactalbumin synthesis in medium depleted of proline. These data suggest that the uncommitted epithelium of virgin mouse mammary glands requires the presence of exogenous proline in order to respond to lactogenic hormonal signals. We have demonstrated earlier that DNA synthesis is a prerequisite of functional differentiation in virgin mouse mammary explants (Smith and Vonderhaar, 1981, Dev. Biol., 88:167-179; Vonderhaar and Smith, 1982, J. Cell Sci, 53:97-114), although cytological differentiation proceeded unencumbered in explants prevented from synthesizing DNA. Here, without proline, neither cytological nor functional differentiation can be induced; this suggests that proline provides an essential metabolic interlock in the acquisition of lactogenic hormone responsiveness in uncommitted mouse mammary tissue.

Animals↗
PubMed1992

Modulation of alveolar type II cell differentiated function in vitro.

We have investigated whether the loss of differentiated function observed in adult rat alveolar type II cells cultured on a substratum that promotes cell spreading and flattening represents a reversible phenotypic change. Cells were cultured for 4 and 8 days in association with fetal rat lung fibroblast feeder layers on either attached collagen gels, which promote the loss of differentiated function, or on floating collagen gels, which support differentiation. A fifth group of cultures were maintained as attached gels for 4 days, then detached and cultured as floating gels for the remaining 4 days. Expression of mRNAs for surfactant proteins A, B, and C, patterns of phospholipid biosynthesis, rates and patterns of protein synthesis, and cell morphology were evaluated as markers of differentiation. Without exception, detaching the gels after 4 days in culture resulted in significant recovery of differentiated characteristics, demonstrating that type II cells modulate differentiated function in response to the culture environment. The results are discussed in relation to the importance of normal cell architecture to normal cell function and to the possible in vitro progression of type II cells to type I cells.

Acetates↗
PubMed1985

Dibutyryl cyclic AMP resistant MDCK cells in serum free medium have reduced cyclic AMP dependent protein kinase activity and a diminished effect of PGE1 on differentiated function.

Prostaglandin E1 (PGE1) has a stimulatory effect both on the growth and the expression of differentiated function of Madin Darby Canine Kidney (MDCK) cells in a hormonally defined medium (Medium K-1). While the stimulatory effect of PGE1 on MDCK cell growth is observed in subconfluent cultures, the effect of PGE1 on differentiated function (i.e., dome formation) is observed at confluency. PGE1 may possibly affect growth and such differentiated functions by separate mechanisms. In order to examine this possibility, dibutyryl cyclic AMP resistant variants of MDCK were selected. All of the variants were partially resistant to the growth inhibitory effects of dibutyryl cyclic AMP and theophylline. The cyclic AMP dependent protein kinase activity of four of the five variant clones studied was significantly reduced as compared with normal MDCK cells. The dependence of the kinase activity of several of the dibutyryl cyclic AMP resistant variants (DBr2 and DBr3) on the cyclic AMP concentration in the reaction mixture was compared with that of normal MDCK cells. At all of the cyclic AMP concentrations tested DBr2 and DBr3 cells had reduced protein kinase activity as compared with normal MDCK cells. This reduced activity could be attributed to a decrease in the Vmax for kinase in the two variants, rather than to a change in the Km of kinase for cyclic AMP. The cyclic AMP phosphodiesterase activity of dibutyryl cyclic AMP resistant variants was also studied. Unlike PGE1 independent clone 1, DBr2 and DBr3 cells did not differ significantly from normal MDCK cells with regard to their ability to degrade cyclic AMP. The growth and functional responsiveness of DBr2 and DBr3 cells to PGE1 was also examined. DBr2 and DBr3 cells were shown to retain a normal growth response to PGE1. However the capacity of DBr2 and DBr3 cells to form domes in response to PGE1 was dramatically reduced as compared with normal MDCK cells. Nevertheless DBr3 cells were shown to still retain the capacity to form domes in response to other inducers. The effect of PGE1 on one of the functional parameters involved in dome formation (the activity of the Na+/K+ATPase) was examined. The rate of ouabain-sensitive Rb+ uptake was observed to be elevated in confluent monolayers of normal MDCK cells maintained in Medium K-1, as compared with monolayers maintained in Medium K-1 minus PGE1.(ABSTRACT TRUNCATED AT 400 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

99mTc-glucoheptonate for quantitation of differential renal function.

Differential renal function was calculated by using 99mTc-glucoheptonate (Tc-GH) in 51 patients. Computer-acquired background-corrected individual renal function was calculated by using both the 1-3-min uptake counts and the 2-4-hr delayed static counts. The degree of correlation between the two was high (r = .96). An equally high correlation was noted in 16 children who were 12 years old or younger, in 15 patients with renal size disparity greater than 60/40%, and in six patients with abnormal creatinine clearances. Ten patients had a 30-min dynamic 99mTc-DTPA study followed immediately by the injection of Tc-GH and acquisition of delayed static images 2-4 hr later. A high degree of correlation (r = .99) was seen between the 1-3-min differential function obtained by using Tc-DTPA and the 2-4-hr delayed differential function obtained by using Tc-GH. This study shows that Tc-GH is a clinically useful and valid tool for calculation of differential renal function and that Tc-GH combines many of the best aspects of Tc-DTPA and Tc-DMSA.

Adolescent↗
PubMed1991

Regulation by growth factors of Leydig cell differentiated functions.

In this paper the effects of growth factors on the differentiated function of pig Leydig cells and other steroidogenic cells are reviewed. Two types of action have been observed, i.e. positive or negative acute effects on testosterone secretion, and long-term trophic effects of hCG receptor and responsiveness to hCG. Among the growth factors, insulin-like growth factor I (IGF-I) and transforming growth factor beta (TGF beta-1) are of particular interest. IGF-I is required for the maintenance and probably the expression of differentiated functions of several steroidogenic cells, including the Leydig cells. TGF beta-1 has effects opposite to IGF-I on Leydig cell functions. When considering effects of growth factors on Leydig cells, caution should be taken in extrapolating results obtained in one species to another.

Animals↗
PubMed1985

Induction of functional differentiation of a human monocytic leukemia cell line (THP-1) by retinoic acid and cholera toxin.

The human monocytic leukemia cell line, THP-1, is induced to differentiate into more functionally mature monocyte (macrophage)-like cells by incubation with retinoic acid at concentrations of 10nM or higher. There is no apparent morphological change accompanying this functional maturation. These induced cells show increases in nitroblue tetrazolium reduction, immunoerythrophagocytosis, hexose monophosphate shunt activity, and 5'-nucleotidase and NAD+-glycohydrolase activities. Prostaglandin E2, dibutyryl cyclic adenosine 3':5'-monophosphate, or T-lymphocyte-derived differentiation-inducing activity, all inactive or less active alone, increase the extent of differentiation of THP-1 in combination with 10nM retinoic acid. THP-1 is also induced to differentiate by 0.1nM or higher concentrations of cholera toxin. Furthermore, 24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 induces less differentiation of THP-1 compared to retinoic acid. Dimethyl sulfoxide and 12-O-tetradecanoylphorbol-13-acetate show no induction of functional differentiation. THP-1 thus joins the list of leukemic myelomonocytic cell lines (e.g., the promyelocytic HL-60 and the monoblast-like U-937) that are blocked at a relatively late stage of maturation and which differentiate in response to retinoic acid.

5'-Nucleotidase↗
PubMed1986

Expression of differentiated functions in kidney epithelial cell lines.

The expression of differentiated functions in long-term cell lines MDCK and LLC-PK1 derived from renal epithelia is briefly summarized. Topics include differentiated transport properties and enzymatic functions expressed by these cell lines, modulation of a differentiated phenotype by exogenous inducers, substratum and cell-cell contact, and possible mechanisms of inducer action.

Acetamides↗
PubMed1990

Phenotypical and functional differentiation of CD4+ CD45RA+ human T cells following polyclonal activation.

Human CD4+ T cells differ in their expression of the leucocyte common antigen. Antibodies detecting certain forms (CD45RA and CD45RO) of this antigen have been used to identify and isolate subpopulations of the CD4+ T cells. These isolated subsets have been shown to have different abilities concerning lymphokine production and provision of help to B cells for Ig production. When these T-cell subsets were activated in vitro with polyclonal activators, the production. When these T-cell subsets were activated in vitro with polyclonal activators, the CD45RA+ cells lost this marker and gained the expression of CD45RO. This was true for all mitogens used in this report, i.e. accessory cell-dependent stimulation with SEA and accessory cell-independent activation with PMA or PHA. A correlation between proliferation and differentiation was observed, but this was probably not causative as stimulation with PMA in the absence of DNA synthesis resulted in the acquisition of CD45RO and loss of the CD45RA antigen. Moreover, cells proliferating vigorously for long periods of time expressed both markers at significant levels, which suggests that proliferation did not automatically result in complete loss of the CD45RA marker. The phenotypical differentiation was associated with a functional differentiation which induced the stimulated cells' ability to act as helper cells for Ig production and to produce gamma interferon (IFN-gamma). The results obtained in this study support the contention that the CD45RA+ cells are precursors of the CD45RO+ cells and that the two subsets represent different maturational stages of the same lineage.

Antigens, Differentiation↗
PubMed1989

Cultivation of adult rat hepatocytes on 3T3 cells: expression of various liver differentiated functions.

Adult rat hepatocytes were maintained in culture for at least 1 month without losing the expression of their differentiated functions; they were cultured on lethally treated 3T3 fibroblasts inoculated at 35,000 cells/cm2 with medium containing 10-25 micrograms/ml hydrocortisone. Hepatocytes showed their typical morphology; they formed bile canaliculi, microvilli, and intercellular junctions with desmosomes and nexus; some formed structures that may resemble the perisinusoidal space of Disse. In addition, they showed DNA synthesis and expressed some liver-specific functions. They synthesized albumin and other proteins, which were exported to the culture medium. Like parenchymal liver cells in vivo, de novo fatty acid synthesis and esterification took place, and more than 80% of the lipids synthesized by the hepatocytes were secreted into the medium as triglycerides; they also showed cytochrome-P450 activity that was inducible with phenobarbital, suggesting that the hepatocytes have the capacity to metabolize drugs. These culture conditions allow the study of various hepatocyte differentiated functions, and they may provide the means to analyze the effect on liver of hormones, viruses and hepatotoxic chemicals and drugs; they may also indicate conditions adequate for serial growth of hepatocytes.

Animals↗
PubMed1991

CCl4 cirrhosis in rats: irreversible histological changes and differentiated functional impairment.

Cirrhosis of the rat liver was induced by a 12 week individualized CCl4/phenobarbital treatment. After treatment, all surviving animals (81%) showed cirrhosis of the liver. The cirrhosis induced was irreversible when evaluated 24 weeks after cessation of treatment. Quantitative liver function measurements were reduced in a differentiated manner. Ranked according to the most pronounced changes they are: capacity of urea-N synthesis (CUNS), galactose elimination capacity (GEC) and antipyrine clearance (APC). Hepatic glutathione concentrations were only slightly decreased after the CCl4 treatment. It is possible to produce a high incidence of irreversible cirrhosis with differentiated functional impairment in the rat.

Animals↗
PubMed1992

The autocrine role of tumor necrosis factor in the proliferation and functional differentiation of human lymphokine-activated T killer cells (T-LAK) in vitro.

The autocrine role of tumor necrosis factor alpha (TNF) in the proliferation and functional differentiation of human lymphokine-activated T-killer cells (T-LAK) in vitro was investigated. Human peripheral blood lymphocytes initially stimulated with IL-2 and phytohemagglutinin-P (PHA) for 48 h will proliferate for long periods in vitro in the presence of IL-2. These T-LAK cells have been shown to be 95% CD3 positive. Employing ELISA techniques, greater than 500 pg/ml of TNF was found to be released in the supernatants of these cells during the first 5 days of culture. However, the levels dropped to 100-200 pg/ml by days 7-10. T-LAK cells grown from days 7 to 10 in the presence of IL-2 and rabbit anti-TNF were significantly growth inhibited (up to 23%). The cytolytic activity of T-LAK cells grown from days 0 to 7 in the presence of anti-TNF was also decreased (up to 75%). Phenotypic analysis of these anti-TNF treated T-LAK cells revealed a decrease in CD8 expression (up to 12%) and increase in CD4 expression (up to 27%) when compared with control cells. The data suggest that TNF has a regulatory role in the growth and functional differentiation of these human T-LAK cells.

CD4 Antigens↗
PubMed1991

Effects of ageing on the growth and differentiated function of transfected human thyrocytes.

Senescence in primary cultures of mammalian cells is characterised by cessation of growth after a number of cell divisions; this may be associated with loss of some differentiated functions. Recent studies on bovine adrenocortical cells have suggested that expression of simian virus-40 (SV40) early region in these cells may prevent phenotypic losses due to senescence. We report here data on growth and differentiated function of two human thyrocyte cell lines (SGHTL-34 and -45) generated by the transfection of primary thyrocytes with the plasmid pSV3neo which contains the SV40 early region. Growth was assessed by fluorometric DNA estimations and calculation of cell population doubling time; function was assessed by binding studies using 125I-bovine thyrotrophin (TSH) and measurement of cyclic adenosine 3',5'-monophosphate (cAMP) response to stimulation with TSH, forskolin and cholera toxin. After 3-12 months in stable culture there was a gradual increase in the doubling time of both cell lines over a 3-month period (SGHTL-34 cells, early 34.5 +/- 4.5 h, late 301 +/- 111.6 h; SGHTL-45 cells, early 53.4 +/- 4.4 h, late 148.3 +/- 26.3 h; mean +/- SEM). Scatchard analysis demonstrated a loss of the high affinity TSH receptor over the same time period. The increase in cAMP in response to 1000 microU/ml TSH declined until the cells became unresponsive (SGHTL-34 early, cAMP 10.3 +/- 0.7 pmol/well; late, cAMP -0.4 +/- 0.3 pmol/well; SGHTL-45 early, cAMP 11.3 +/- 1.1 pmol/well, late, cAMP 0.3 +/- 0.1 pmol/well). The cAMP responses to forskolin and cholera toxin were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1985

The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate enhances the long-term maintenance of pancreatic islet B cell differentiated function in tissue culture.

A study was undertaken to examine the effects of the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, on pancreatic islet B cell differentiated function and number. Islets from 3-day-old rats were maintained in tissue culture for up to 30 days with or without the addition of the phorbol ester. Changes in the insulin content of the media and tissue were determined at 48 hr and weekly intervals, respectively, using radioimmunoassay. The 30-day cumulative output of insulin into the medium was increased almost 2-fold and the tissue insulin content was increased 4-fold by the phorbol ester. Counts of cell smears processed for the immunocytochemical localization of insulin indicated no effect on the total numbers of B cells or non-B cells in either control or treated cultures. This enhanced maintenance of islet B cell differentiated function by 12-O-tetradecanoylphorbol-13-acetate suggests that pancreatic islets may be a useful model with which to study the mechanisms of action of this and other tumor-promoters.

Animals↗