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S Susini

Publications and source records attributed to S Susini.

14 recordsLinked to original sources
PubMed2000

Essentiality of intron control in the induction of c-fos by glucose and glucoincretin peptides in INS-1 beta-cells.

Glucose controls long-term processes in the pancreatic beta-cell such as metabolic enzymes gene expression, cell growth, and apoptosis. Such control is likely mediated via the expression of immediate-early response genes since several of these genes including c-fos are strongly induced by glucose in the beta-cell line INS-1, provided costimulation with cAMP-raising glucoincretin hormones. This study addresses the mechanism of c-fos gene activation by glucose. Glucose in the presence of chlorophenylthio-cAMP generated a low threefold induction of the c-fos/basic luciferase reporter gene, which includes only the c-fos promoter. In contrast, the c-fos/intron construct containing the first intron in addition to promoter elements showed a pronounced 16-fold induction, comparable to the increased c-fos mRNA accumulation. Similar observations were made with glucose in combination with the glucoincretins glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and pituitary adenylyl cyclase-activating peptide 38. Deletion of a 119 bp region in intron 1 that includes a transcriptional arrest site did not affect the inductive process. In contrast, a 534 bp deletion comprising a major part of the intron reduced the induction by 75%. At the promoter level, mutating the cAMP response element reduced by more than 60% the transcriptional activation whereas mutating the serum response element had no effect. Inhibitors of protein kinase A and Ca(2+)/calmodulin-dependent protein kinases each reduced by 50% the reporter gene activation and together fully prevented the glucose-glucoincretin effect. In conclusion, the strong induction of c-fos by glucose and glucoincretins results from Ca(2+) and cAMP signaling pathways addressing both the CRE in the promoter and essential response element(s) in the first intron that are unrelated to the transcription arrest site.

Base Sequence↗
PubMed1999

Glucagon-like peptide-1 promotes DNA synthesis, activates phosphatidylinositol 3-kinase and increases transcription factor pancreatic and duodenal homeobox gene 1 (PDX-1) DNA binding activity in beta (INS-1)-cells.

AIMS/HYPOTHESIS: Glucagon-like peptide-1 is a potent glucoincretin hormone and a potentially important drug in the treatment of Type II (non-insulin-dependent) diabetes mellitus. We have investigated whether it acts as a growth factor in beta (INS-1)-cells and have studied the signalling pathways and transcription factors implicated in this process. METHODS: Cell proliferation was assessed by tritiated thymidine incorporation measurements. We have examined the action of glucagon-like peptide-1 on the enzymatic activity of phosphatidylinositol 3-kinase. The DNA binding activity of transcription factors was investigated by electrophoretic mobility shift assay. Measurements of mRNA were done using the northern technique. RESULTS: Glucagon-like peptide-1 caused an increase in tritiated thymidine incorporation in beta (INS-1)-cells and phosphatidylinositol 3-kinase activity in a dose-dependent manner non-additively with glucose. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 blocked the effects of glucagon-like peptide-1 on DNA synthesis. Transcription factor pancreatic and duodenal homebox gene 1 (PDX-1) DNA binding activity was increased by glucagon-like peptide-1 at 3 or 11 mmol/l glucose and the phosphatidylinositol 3-kinase inhibitor LY294002 suppressed the action of glucagon-like peptide-1 on PDX-1 DNA binding activity. Glucagon-like peptide-1 and glucose alone did not change activating protein-1 DNA binding activity. They synergised, however, to increase the activity of activating protein-1. Glucagon-like peptide-1 also increased the expression of PDX-1, glucose transporter 2, glucokinase and insulin mRNAs. Finally, glucagon-like peptide-1 increased the incorporation of tritiated thymidine in isolated rat islets. CONCLUSION/INTERPRETATION: The results suggest that glucagon-like peptide-1 may act as a growth factor for the beta cell by a phosphatidylinositol 3-kinase mediated event. Glucagon-like peptide-1 could also regulate the expression of the insulin gene and genes encoding enzymes implicated in glucose transport and metabolism through the phosphatidylinositol 3-kinase/PDX-1 transduction signalling pathway.

Androstadienes↗
PubMed1998

Glucose and glucoincretin peptides synergize to induce c-fos, c-jun, junB, zif-268, and nur-77 gene expression in pancreatic beta(INS-1) cells.

To link glucose signaling to its long-term pleiotropic effects in the pancreatic beta-cell, we have investigated whether glucose regulates immediate-early response genes (IEGs) coding for transcription factors implicated in cell proliferation and differentiation. Glucose causes a coordinated transcriptional activation of the IEGs c-fos, c-jun, JunB, zif-268, and nur-77 in the pancreatic beta-cell line INS-1. This activation is entirely dependent on the presence of the cell-permeant cAMP analog chlorophenylthio-cAMP, which has only a modest effect by itself. The accumulation of c-fos, JunB, and nur-77 mRNA occurs at physiological concentrations of glucose (3 to 11 mM), requires a 1-2 h period, and is mimicked by other nutrient stimuli including mannose, leucine plus glutamine, and pyruvate. Glucose is synergistic with the glucoincretin peptides GLP-1 and PACAP-38, whereas these neurohormonal agents have no effect at low (3 mM) glucose. Mechanistically, the synergy between glucose and the glucoincretins is not based on cAMP alone as glucose does not further increase intracellular cAMP in response to GLP-1 and PACAP-38. A role for Ca2+ signaling is inferred, since the L-type Ca2+ channel blocker nifedipine markedly reduces the induction of c-fos and nur-77 by glucose and GLP-1. The induction of IEGs by glucose and chlorophenylthio-cAMP or GLP-1 and the inhibitory effect of nifedipine are also observed in the betaHC9 cell line. The results indicate that GLP-1 and PACAP-38 act as competence factors for the action of glucose on c-fos, JunB, and nur-77. It is suggested that the synergistic effect of glucose and glucoincretins on IEG expression plays an important role in the adaptive processes of the beta-cell to hyperglycemia.

Animals↗
PubMed1995

Modifications in uterine and intraovarian artery impedance in cycles of treatment with exogenous gonadotropins: effects of luteal phase support.

OBJECTIVE: To determine the effects of induction of multiple ovulation and of luteal P supplementation on the impedance to blood flow in the uterine and intraovarian arteries during the luteal phase. DESIGN: A prospective study using transvaginal color flow Doppler imaging. SETTING: A university-based infertility center. PATIENTS: Fifty-six women with unexplained or male factor-related infertility undergoing IUI. INTERVENTIONS: The patients were studied either during spontaneous cycles (n = 16) or in cycles of induction of multiple follicular development with purified FSH (n = 40). In 18 treated cycles, the luteal phase was supplemented with natural P. MAIN OUTCOME MEASURES: The pulsatility index was recorded from uterine and intraovarian arteries on the day of E2 peak and 5 and 10 days thereafter. On the same days, E2 and P plasma levels were measured by RIA. RESULTS: The intraovarian pulsatility index was significantly lower in FSH-treated than in spontaneous cycles on the day of E2 peak. Also, the uterine pulsatility index was significantly lower in treated cycles than in spontaneous cycles on the day of E2 peak and 5 days thereafter. In the late luteal phase, P supplementation was correlated with a significant decrease in uterine pulsatility index as compared with both spontaneous cycles and FSH-treated cycles without luteal support. CONCLUSIONS: Multiple follicular development is associated with a significant reduction in the impedance to perifollicular blood flow. Progesterone, as well as E2, seems able to decrease the impedance to blood flow in uterine arteries in women.

Adult↗
PubMed1991

Mycobacterium xenopi isolation from clinical specimens in the Florence area: review of 46 cases.

The occurrence of Mycobacterium xenopi (MX) isolates is not homogeneous in various geographic zones. In the Florence area, between 1975-1989, strains of MX from 64 different patients have been isolated. The review of bacteriological and clinical data of 46 of them, from whose sputum MX had been grown, allowed to diagnose for 26% the commensal nature of this finding, for 41% the concomitance with a tubercular infection and for the remaining 33% the pathogenicity of this microorganism. The increased occurrence of MX isolates, their high rate of pathogenicity and the remarkable homogeneity of their biochemical, cultural and antimicrobial sensitivity patterns seem to suggest the hypothesis of an endemic focus of this species in the Florence area.

Anti-Bacterial Agents↗
PubMedDate not supplied

Calcium signalling and gene expression.

A wide variety of compounds acting as extracellular signals cause changes in the free cytosolic Ca2+ concentration. These factors include hormones, growth factors, neurotransmitters, but also nutrient and metabolic activators. Ca2+ signalling is caused by mobilization of Ca2+ from internal stores and by well controlled and timed Ca2+ influx from the extracellular space. Ca2+ signals address Ca2+ dependent enzymes, most importantly Ca2+ sensitive protein kinases and phosphatases. The profound influence of Ca2+ signalling on gene expression has been recognized a long time ago. As Ca2+ signals are short-lived when compared to alterations in differentiated gene expression, it is generally considered that genes coding for short-lived transcription factors (i.e. fos, jun) are the immediate target of Ca2+ signalling. Transcription of these immediate early genes (IEG) can be activated without the need for protein synthesis. Ca2+ signalling affects differentiated gene expression via changes in the absolute and relative abundance of IEG products, which in turn control the expression of differentiated genes. Ca2+ signals can stimulate both transcriptional initiation as well as transcriptional elongation. Initiation of transcription is stimulated by the Ca2+ dependent phosphorylation of binding proteins addressing two response elements in the promoter of IEGs: the cAMP response element, CRE, and the serum response element, SRE. Distinct protein kinases are involved in either case. We study the elongation of transcripts of the IEG c-fos beyond the first intron which is favoured by Ca2+ signals, involving mechanisms which still are poorly understood. We can show that intron sequences contribute to the control of elongation by Ca2+, and that there is a strong interrelation between the transcription control by the promoter and by the intron.

Animals↗
PubMedDate not supplied

[Histogenetic problems of a "granular cell tumor" in the trachea].

On the possible ontogeny of the cells of a "granular cell tumor" of the human trachea. In a young patient affected with pulmonary tuberculosis during bronchoscopy a "granular cell tumor" of the membranous part of trachea was occasionally evidentied. After pathologic examination, the specimen is analyzed in order to assess the kind of cells that are present in the lesion: the ultrastructural and immunohistochemical study shows Schwann cells which particularly well developed lysosomal complement.

Adult↗