Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Formation and secretion of insulin during administration of tetracycline hydrochloride in vivo and in vitro were studied in experimental rat Langerhans islets isolated by enzymatic digestion with collagenase. Insulin secretion was determined by radioimmunoassay, insulin biosynthesis was assessed from 3H-leucin incorporation into the de novo formed proteins of the islets with insulin immunoreactivity (proinsulin plus insulin). Injection of the antibiotic in a dose of 25 mg/kg intraperitoneally for 10 days did not change the functional activity of beta-cells--the rate of insulin formation and secretion at low and high glucose concentrations in the incubation medium. Higher doses of the antibiotic applied in vivo (100 mg/kg intraperitoneally for 10 days) and in vitro (100 mumol, 2-hour incubation) inhibited the glucose-stimulated (15 mmol) insulin secretion but exerted no effect on insulin biosynthesis. The possible importance of ionophore properties of the antibiotic, that changes the concentration of intracellular Ca2+ in the mechanism of dissociated action of tetracycline hydrochloride on insulin formation and secretion, as well as the practical significance of the data obtained are discussed.
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PMID:[Biosynthesis and secretion of insulin under the effect of an antibiotic of the tetracycline group]. 636 1

HB 699 belongs to a new class of hypoglycaemic agents, the acyl-amino-alcyl-benzoic acids. Its influence on bion-synthesis and secretion of insulin was studied in collagenase-isolated rat islets. During incubations for 3 hours together with 3H-leucine at 1 and 2 mg/ml glucose, HB 699 (10 micrograms/ml) reduced biosynthesis of proinsulin and insulin (3H-leucine incorporation), whereas insulin release was stimulated. During an incubation period of 2 hours in the absence of glucose, insulin release was enhanced both by HB 699 (50 micrograms/ml) and glibenclamide (10 micrograms/ml). At 1 mg/ml glucose, no additive or potentiating effect of HB 699 to that of glibenclamide was found regarding insulin release. When calcium ions were omitted insulin output in the presence of HB 699 and glucose was reduced. In conclusion, HB 699, although not belonging to the class of sulfonylureas, behaves very similar to these drugs concerning its influence on insulin biosynthesis and secretion in vitro. It acts as an initiator of insulin release, involving probably similar mechanisms as sulfonylureas do.
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PMID:The influence off an acyl-amino-alcyl-benzoic acid (HB 699) on biosynthesis and secretion of insulin in isolated rat islets of Langerhans. 678 16

Activation of protein kinase C (PKC) by the phorbol ester 4 beta-phorbol myristate acetate (4 beta-PMA) stimulated (pro)insulin biosynthesis in collagenase-isolated rat islets of Langerhans, as assessed by measuring the incorporation of [35S]cysteine into proinsulin and insulin after fractionation by high performance liquid chromatography. The stimulatory effects of 4 beta-PMA were observed at a substimulatory concentration of glucose (2 mM) but were not additive to the stimulatory effects of 20 mM glucose on insulin biosynthesis. Prolonged exposure to 4 beta-PMA caused a marked down-regulation of PKC activity in islets. PKC-depleted islets showed a much reduced biosynthetic response to 20 mM glucose, but this was caused, at least in part, by an enhanced basal rate of (pro)insulin synthesis. These elevations in the basal rate of insulin synthesis were not secondary to an increase in the amount of preproinsulin mRNA in PKC-depleted islets since Northern blot analysis showed that prolonged exposure to 4 beta-PMA, and the subsequent loss of PKC activity, did not detectably alter basal levels of preproinsulin mRNA. These results suggest that the activation of PKC stimulates (pro)insulin synthesis in rat islets by enhancing translation of existing preproinsulin mRNA, and that this may play some part in the biosynthetic responses of beta-cells to glucose.
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PMID:The role of protein kinase C in insulin biosynthesis. 821 66

Insulin-like growth factors I and II are peptides with a structural homology for proinsulin, and are involved in hepatocyte proliferation. IGF-I and IGF-II, however, have different metabolic roles, and their mechanisms of action are incompletely known. We hypothesized that IGF-I and IGF-II act by different signal transduction pathways. To test this hypothesis, hepatocytes from 200 g male Sprague-Dawley rats were isolated by a two-step collagenase perfusion technique and plated at a density of 10(5) cells/16 mm Primaria plate. Proliferation was measured by [3H]thymidine ([3H]thy) incorporation into DNA, and an autoradiographic nuclear labeling index (LI). To analyze signal transduction, cyclic AMP (cAMP) levels were measured 5 min after addition of reagents by a radioimmunoassay. Reagents (doses) used were: IGF-I (2 nM), IGF-II (2 nM), the inhibitory peptide somatostatin-14 (SS14) (10 nM), and the adenylyl cyclase antagonist dideoxyadenosine (DDA) (10 microM). A summary of the findings is as follows: (1) IGF-I stimulates [3H]thy, LI and cAMP accumulation. (2) IGF-II stimulates [3H]thy and LI but not cAMP; (3) IGF-I but not IGF-II effects are inhibited by SS14 and DDA. We conclude that the hepatotrophic effects of IGF-I and IGF-II occur by different mechanisms: IGF-I is cAMP-dependent, IGF-II is cAMP-independent.
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PMID:Divergent mechanisms of insulin-like growth factor I and II on rat hepatocyte proliferation. 857 Aug 60

In order to explore the feasibility of inducing the human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) to differentiate into insulin-secreting cells with biological products alone, hUC-MSCs were separated and purified from the whole umbilical cord by the sequent digestion of collagenase II and trypsin followed by two-step centrifugation. hUC-MSCs were induced with IMDM culture medium containing epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and Ginkgo biloba extract (GBE). Before and after the induction, the morphological changes were observed under inverse microscope; the islet-related genes were detected by RT-PCR; islet-like clusters (ILCs) were identified by dithizone (DTZ) staining; PDX-1 and immunoreactive insulin (IRI) were examined by immunofluorescence method; the quantity and quality of IRI secretion were assayed by chemiluminescence immunoassay and Western blot respectively. The results showed that the purified hUC-MSCs presented long spindle-like shape and parallel or spiral arrangement which are typical morphological features of MSCs. After the induction, hUC-MSCs changed gradually into round or oval shape and gathered together to form ILCs; there were more than one hundred clusters on the growth surface of a flask of T25; ILCs were stained into positive mauve by DTZ and positive for PDX-1 and IRI; Western blot displayed that most of the IRI was proinsulin (PI). Therefore, hUC-MSCs can rapidly differentiate into insulin-secreting cells under the sole induction of EGF, bFGF, GBE and IMDM, but ILCs are not mature enough to produce sufficient true insulin.
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PMID:[Rapid differentiation of human umbilical cord-derived mesenchymal stem cells into insulin-secreting cells under the sole induction of biological products]. 2017 92

The study was conducted to evaluate the association between MMP-1 (rs1799750)-1607 1G/2G and MMP-3 (rs3025058)-1612 5A/6A polymorphisms/haplotypes and coronary artery disease (CAD) risk among Iranian Turks. Totally, 102 patients with CAD and 102 healthy subjects joined the study. Genomic DNA isolation was carried out using "salting out" method from 3 to 4 mL of whole blood samples. The MMP-1 (-1607 2G/1G) and MMP-3 (-1612 5A/6A) promoter gene polymorphisms were detected via polymerase chain reaction restriction fragment length polymorphism. Our results indicated that the frequencies of the MMP-1 (-1607) 2G alleles and 2G/2G genotypes and the MMP-3 (-1612) 6A alleles and 6A/6A genotypes were higher in CAD patients older than 50 years than in healthy controls (P < 0.05). We failed to show statistically significant differences between the CAD patients younger than 50 years and controls concerning MMP-1 -1607 ins/delG (1G > 2 G, rs1799750) and MMP-3 -1612 ins/delA (5A/6A, rs3025058) polymorphisms (P > 0.05). The frequencies of MMP-3/MMP-1 haplotypes were not statistically different among tested groups (P > 0.05). This examination, as the first study of its own kind in Iranian Turks, reported association between MMP-1 (rs1799750) -1607 2G/2G and MMP-3 (rs3025058) -1612 6A/6A genotypes and CAD risk in patients older than 50 years.
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PMID:Association of MMP-1 (rs1799750)-1607 2G/2G and MMP-3 (rs3025058)-1612 6A/6A Genotypes With Coronary Artery Disease Risk Among Iranian Turks. 3135 34


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