Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octreotide (SMS), a somatostatin analogue, is an established antigrowth peptide, but it does not effectively inhibit the growth of insulinoma cells. In order to study the mechanisms that underlie this apparent lack of an antiproliferative effect on insulinoma tumor cells we established the rat insulinoma cell line, RINm5F, in culture. Cells in culture were tested by incubation in media with and without SMS. To study tritiated [3H]-thymidine incorporation into extracted DNA (TTID), 2 muCi/well of 3H was added for 24 hr, and cells were harvested and assayed for TTID (cpm/microgram DNA). Insulin (IRI) and intracellular cAMP (cAMPi) were measured by RIA. To study the effects of SMS on insulin secretion, conditioned media were sampled after 24 hr. To study the effects of cAMPi, conditioned medium was used to extract cAMPi following incubation with SMS for 15 min. Increasing concentrations of SMS had no significant effect on TTID in the presence of 1% FBS. Trypan blue exclusion tests showed > 90% viable cells throughout all stages of these experiments. There were no significant differences in cell numbers and protein content in the presence of SMS. There was a significant decrease in the secretion of insulin and intracellular cAMP levels in response to 50 nM SMS. However, SMS significantly inhibited TTID in RINm5F cells following a 4-hr pretreatment with pertussis toxin (PT) (23553 +/- 1747 vs 20635 [cpm/microgram DNA] +/- 1983 [SEM], P < 0.01). We conclude that the inhibition of insulin secretion by SMS is associated with an attenuation of cAMP formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of somatostatin action in RINm5F cells in culture: preliminary evidence for possible altered G protein function. 135 94

In mammary epithelial cells (MEC) TGF-beta(1) is the auto-/paracrine growth inhibitor and inducer of apoptosis and therefore is considered as an important local regulator of mammary tissue involution. However, the mechanisms of controlled TGF-beta(1) expression in the course of bovine mammary gland remodelling are still unclear. Recent study performed in this laboratory support the evidence that TGF-beta(1) expression in bovine MEC is regulated by hormones of somatotropic axis (GH, IGF-I and somatostatin). Present study was focused on the contribution of IGF-I-induced signaling pathways in anti-TGF-beta(1) and anti-apoptotic effects of IGF-I. Laser scanning cytometry was applied for the measurement of TGF-beta(1) content and apoptotic cell number in bovine BME-UV1 MEC. Involution of the bovine mammary gland in vitro was modeled by decreasing the availability of FBS for bovine MEC. Reducing FBS content in the medium from 10% to 0.5% evoked highly significant increase of TGF-beta(1) expression and increase of apoptotic cell number. IGF-I (50 ng/ml) completely abrogated FBS deficiency-induced TGF-beta(1) expression and apoptosis in bovine MEC. In order to establish which of the IGF-I signaling pathways contributed to anti-TGF-beta(1) and anti-apoptotic effects, the inhibitors of PI3-kinase - (LY 294002) and MEK- (MAPKK for ERK) (PD 098059) mediated signaling pathways were applied to our model. The results clearly showed that inhibition of PI3-K reverses the ability of IGF-I to suppress TGF-beta(1) expression and apoptosis. An inhibition of ERK1/2 pathway even potentiated inhibitory effect of IGF-I on TGF-beta(1) expression, but partially abrogated anti-apoptotic effect of IGF-I. In conclusion, the results of the study indicate that PI3-K/Akt pathway contributed significantly to the inhibition of TGF-beta(1) expression by IGF-I, whereas both PI3-K/Akt and ERK1/2 pathways are involved in the anti-apoptotic effect of IGF-I in bovine MEC.
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PMID:Dissimilar effects of LY 294002 and PD 098059 in IGF-I-mediated inhibition of TGF-beta1 expression and apoptosis in bovine mammary epithelial cells. 1607 2