scholarly journals The effect of sugars on (pro)insulin biosynthesis

1978 ◽  
Vol 174 (2) ◽  
pp. 517-526 ◽  
Author(s):  
Stephen J. H. Ashcroft ◽  
Judy Bunce ◽  
Martin Lowry ◽  
Svend E. Hansen ◽  
Carl J. Hedeskov
Keyword(s):  
Cyclic Amp ◽  
Insulin Release ◽  
Total Protein ◽  
Glucose Sensor ◽  
Protein Biosynthesis ◽  
Insulin Biosynthesis ◽  
Site Model ◽  
Low Concentrations ◽  
Glucose Analogues ◽  
Stimulation Of

Rates of incorporation of [4,5-3H]leucine into insulin plus proinsulin, designated ‘(pro)insulin’, and total protein in rat pancreatic islets were measured. Glucose stimulates rates of total protein and (pro)insulin biosynthesis, but (pro)insulin biosynthesis is stimulated preferentially. Mannose and N-acetylglucosamine also stimulate (pro)insulin and total protein biosynthesis; inosine and dihydroxyacetone stimulate (pro)insulin biosynthesis specifically. Fructose does not stimulate (pro)insulin biosynthesis when tested alone, but does so in the presence of low concentrations of glucose, mannose or N-acetylglucosamine. Many glucose analogues do not stimulate (pro)insulin biosynthesis. Mannoheptulose inhibits synthesis of (pro)insulin and total protein stimulated by glucose or mannose but not by dihydroxyacetone, inosine or N-acetylglucosamine; phloretin (9μm) inhibits N-acetylglucosamine-stimulated (pro)insulin biosynthesis preferentially. The data are in agreement with the view that the same glucose-sensor mechanism may control both insulin release and biosynthesis, and ‘substrate-site’ model is suggested. The threshold for stimulation of biosynthesis of (pro)insulin and total protein is lower than that found for glucose-stimulated insulin release; moreover the biosynthetic response to an elevation of glucose concentration is slower than that found for insulin release. The physiological implication of these findings is discussed. Caffeine and isobutylmethylxanthine, at concentrations known to increase islet 3′:5′-cyclic AMP and potentiate glucose-induced insulin release, were without effect on rates of glucose-stimulated (pro)insulin biosynthesis.

scholarly journals Effect of interferon and double-stranded RNA on B-cell function in mouse islets of Langerhans

1985 ◽  
Vol 228 (1) ◽  
pp. 87-94 ◽  
Author(s):  
C J Rhodes ◽  
K W Taylor
Keyword(s):  
Insulin Release ◽  
Cell Function ◽  
Protein Biosynthesis ◽  
Insulin Biosynthesis ◽  
Double Stranded Rna ◽  
Mouse Pancreatic Islets ◽  
Mouse Islets ◽  
Stimulation Of ◽  
Slight Inhibition

The direct effects of alpha- and beta-interferons on isolated mouse pancreatic islets were investigated in vitro and found to be similar. After 7 h incubation with interferon concentrations above 350 units/ml, glucose-stimulated (pro)insulin biosynthesis was significantly inhibited, with only a slight inhibition of total protein biosynthesis. Inhibition could be abolished in the additional presence of an anti-interferon antibody. Interferon did not affect insulin release, total insulin content, or glucose oxidation of the islets. The stimulation of (pro)insulin biosynthesis by adenosine, D-glyceraldehyde, mannose, N-acetylglucosamine and leucine was also inhibited by interferon, with no effect on insulin release. At concentrations of dsRNA (double-stranded RNA) said to induce interferon (1-100 micrograms/ml), glucose-stimulated (pro)insulin biosynthesis was inhibited without significantly affecting insulin release. The dsRNA may itself inhibit stimulated (pro)insulin biosynthesis or may function indirectly by the induction of interferon.

Effect of lanthanum on the inotropic response of isoproterenol: role of the superficially bound calcium

1985 ◽  
Vol 63 (9) ◽  
pp. 1106-1112 ◽  
Author(s):  
Ahmad B. Fawzi ◽  
John H. McNeill
Keyword(s):  
Cyclic Amp ◽  
Positive Inotropic Effect ◽  
Direct Action ◽  
Maximum Response ◽  
Inotropic Response ◽  
Guinea Pig Heart ◽  
Low Concentrations ◽  
Stimulation Of ◽  
Calcium Pool

Mammalian myocardial contractility is believed to be related to the amount of calcium contained in a highly labile superficial calcium pool. The purpose of this study was to determine the role of such sites in the positive inotropic effect of isoproterenol. Lanthanum, an ion that is restricted to the extracellular space and that displaces the superficially bound calcium, was selected as a tool for this investigation. In Langendorff preparations of the guinea pig heart, lanthanum decreased the basal contractility index (+ dP/dtmax) in a concentration-dependent fashion (0.05–3μM) and blocked the inotropic response of isoproterenol in a noncompetitive manner (0.25–3 μM). Three-micromolar lanthanum (i) reduced basal contractility and the maximum response to isoproterenol by 97 and 95%, respectively, (ii) had no significant effect (p > 0.05) on basal and isoproterenol-induced cyclic AMP levels, and (iii) had no effect on the Kd of [3H]nitrendipine binding, but reduced the Bmax by 31%. While 1 μM lanthanum reduced basal contractility and the maximum response to isoproterenol by 90 and 70%, respectively, it had no effect on [3H]nitrendipine binding. These results suggest that the effects of such low concentrations of lanthanum (≤3 μM) are not related to a direct action on the calcium channels and are not mediated by an inhibition of isoproterenol stimulation of the enzyme adenylate cyclase. Therefore, one interpretation of these results suggests that superficially bound calcium is required for the inotropic response of isoproterenol.

Low concentrations of interleukin-1 stimulate and high concentrations inhibit insulin release from isolated rat islets of Langerhans

1986 ◽  
Vol 113 (4) ◽  
pp. 551-558 ◽  
Author(s):  
Giatgen A. Spinas ◽  
Thomas Mandrup-Poulsen ◽  
Jens Mølvig ◽  
Leif Bæk ◽  
Klaus Bendtzen ◽  
...  
Keyword(s):  
Insulin Release ◽  
Interleukin 1 ◽  
Insulin Biosynthesis ◽  
Rat Islets ◽  
Low Concentrations ◽  
Isolated Rat Islets ◽  
High Concentrations ◽  
Rat Islets Of Langerhans ◽  
Isolated Rat

Abstract. Isolated rat islets were incubated either with crude, affinity-purified or recombinant human interleukin-1 for 1 to 6 days. A significant (20–60%) increase of insulin release was observed at low concentrations of all three interleukin-1-containing preparations. In contrast, higher concentrations dose-dependently inhibited the insulin release. The increased insulin secretion occurred at concentrations below those necessary to augment the mitogen response to phytohaemagglutinin of murine thymocytes in vitro. These doses (0.05-0.5 U/ml) correspond to 0.2-2 ng of recombinant interleukin-1 per ml, equal to approximately 0.01-0.1 pmol/ml. In doses of 0.6-1.8 U/ml affinitypurified interleukin-1 significantly increased the islet insulin content per ng of DNA, indicating a stimulation of insulin-biosynthesis. The data support the concept that low concentrations of interleukin-1 may play a role in priming the physiological secretion of insulin.

Morphology, yield and functional integrity of islet-like cell clusters in tissue culture of human fetal pancreata obtained after different means of abortion

1988 ◽  
Vol 118 (1) ◽  
pp. 68-76 ◽  
Author(s):  
Timo Otonkoski ◽  
Mikael Knip ◽  
Pertti Panula ◽  
Sture Andersson ◽  
Inés Wong ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Total Protein ◽  
Culture Medium ◽  
Protein Biosynthesis ◽  
Fold Increase ◽  
Insulin Biosynthesis ◽  
Cell Clusters ◽  
Different Types ◽  
Induced Abortions ◽  
And Function

Abstract. Morphology, yield and function were studied in cultured islet-like cell clusters (ICC) from 140 human fetal pancreata obtained after abortions of different types performed at 11–23 weeks of gestation (12 by hysterotomy, 75 by mechanical dilation and extraction, and 53 induced with prostaglandin). After collagenase digestion and culture in medium supplemented with 10% human serum, up to 2000 free-floating ICC were formed from a single pancreas. Randomly scattered insulin- and glucagon-immunoreactive cells were found in the medullary part of the ICC. More than 100 ICC developed in 100% of the hysterotomies and 87% of the mechanical abortions, but in only 53% of the prostaglandin-induced abortions. Insulin and glucagon levels in the culture medium decreased rapidly during the first 7 days of culture, but then remained stable for at least 31 days. The hysterotomy-derived ICC responded to 10 mmol/l theophylline plus 20 mmol/l glucose by a 12.2 ± 3.1 (sem, N = 7) fold increase in insulin release, as compared with a 5.4 ± 0.9 fold response of the prostaglandin ICC (N = 16; P < 0.02). Despite the low proportion of B-cells, (pro)insulin biosynthesis accounted for 10% of the total protein biosynthesis in low (2 mmol/l) glucose. In conclusion, the yield and viability of the ICC were clearly better, if prostaglandin had not been used for the induction of the abortion.

scholarly journals Adenosine 3':5'-monophosphate content and actions in the division cycle of synchronized HeLa cells.

1976 ◽  
Vol 71 (2) ◽  
pp. 515-534 ◽  
Author(s):  
C E Zeilig ◽  
R A Johnson ◽  
E W Sutherland ◽  
D L Friedman
Keyword(s):  
Cell Cycle ◽  
Cyclic Amp ◽  
Hela Cells ◽  
S Phase ◽  
Intracellular Camp ◽  
Specific Effects ◽  
Low Concentrations ◽  
High Concentrations ◽  
Camp Levels ◽  
Stimulation Of

The involvement of adenosine 3':5'-monophosphate (cAMP) in the regulation of the cell cycle was studied by determining intracellular fluctuations in cAMP levels in synchronized HeLa cells and by testing the effects of experimentally altered levels on cell cycle traverse. Cyclic AMP levels were lowest during mitosis and were highest during late G-1 or early S phase. These findings were supported by results obtained when cells were accumulated at these points with Colcemid or high levels of thymidine. Additional fluctuations in cAMP levels were observed during S phase. Two specific effects of cAMP on cell cycle traverse were found. Elevation of cAMP levels in S phase or G-2 caused arrest of cells in G-2 for as long as 10 h and lengthened M. However, once cells reached metaphase, elevation of cAMP accelerated the completion of mitosis. Stimulation of mitosis was also observed after addition of CaCl2. The specificity of the effects of cAMP was verified by demonstrating that: (a) intracellular cAMP was increased after exposure to methylisobutylxanthine (MIX) before any observed effects on cycle traverse; (b) submaximal concentrations of MIX potentiated the effects of isoproterenol; and (c) effects of MIX and isoproterenol were mimicked by 8-Br-cAMP. MIX at high concentrations inhibited G-1 traverse, but this effect did not appear to be mediated by cAMP. Isoproterenol slightly stimulated G-1 traverse and partially prevented the MIX-induced delay. Moreover, low concentrations of 8-Br-cAMP (0.10-100 muM) stimulated G-1 traverse, whereas high concentrations (1 mM) inhibited. Both of these effects were also observed with the control, Br-5'-AMP, at 10-fold lower concentrations.

scholarly journals Polyamines and insulin production in isolated mouse pancreatic islets

1988 ◽  
Vol 252 (3) ◽  
pp. 701-707 ◽  
Author(s):  
N Welsh ◽  
A Sjöholm
Keyword(s):  
Insulin Release ◽  
High Glucose ◽  
Glucose Concentration ◽  
Culture Media ◽  
Protein Biosynthesis ◽  
Insulin Biosynthesis ◽  
Cell Physiology ◽  
High Glucose Concentration ◽  
Insulin Production

The aim of the present study was to evaluate the role of polyamines in the metabolism and insulin production of pancreatic-islet cells. For this purpose islets were prepared from adult mice and used either immediately or after tissue culture. There was a significant decrease in the islet content of spermidine during culture, although the effect was less pronounced in a high glucose concentration. Furthermore, a stimulatory effect of a high glucose concentration, as compared with low guclose, on the content of spermine was observed. To elucidate further the role of polyamaines in beta-cell physiology, the ornithine decarboxylase inhibitors difuoromethylornithine (DFMO) and methylacetylenic putrescine (MAP) and the S-adenosylmethionine decarboxylase inhibitor ethylglyoxal bis(guanylhydrazone) (EGBG) were added to the culture media. Addition of DFMO together with MAP decreased the cellular contents of putrescine and spermidine, whereas the content of sperimine was unaffected. When EGBG was added in combination with DFMO and MAP, there was a decrease in the content of spermine also. Cell viability in the islets depleted of their polyamine contents was not impaired, as assessed by determinations of oxygen-uptake rates and ATP contents. Depletion of putescine plus spermidine by addition of DFMO+MAP was associated with decreased biosynthesis of (pro)insulin and total protein. When the content of spermine was decreased also by the further addition of EGBG, the decrease in (pro) insulin biosynthesis was more pronounced and was paralleled by a decrease in the insulin-mRNA content. Under these conditions, the glucose-stimulated insulin release, the insulin content and the rates of islet DNA synthesis were also decreased. It is concluded that putrescine and spermidine are necessary for the maintenance of normal insulin and protein biosynthesis, whereas spermine may exert a role in some other cellular processes, such as DNA replication, RNA transcription and glucose-stimulated insulin release.

scholarly journals Corticotropin regulation of the synthesis of a specific rat adrenal cytosolic protein. Effects of hypophysectomy and actinomycin D

1979 ◽  
Vol 182 (3) ◽  
pp. 717-725 ◽  
Author(s):  
Alice Dazord ◽  
Dominique Gallet ◽  
Helene Cohen ◽  
Jose M. Saez
Keyword(s):  
Protein Synthesis ◽  
Cyclic Amp ◽  
Total Protein ◽  
Actinomycin D ◽  
Polyacrylamide Gel Electrophoresis ◽  
Cytosolic Protein ◽  
And Control ◽  
Corticotropin Stimulation ◽  
Stimulation Of

The mechanism of corticotropin stimulation of the synthesis of a specific rat adrenal cytosolic protein was investigated. This protein (protein E) has a mol.wt. of approx. 30000. It is detected by polyacrylamide-gel electrophoresis of cytosol prepared from adrenal slices from rats treated with corticotropin in vivo and control rats, the slices being incubated with [3H]- and [14C]-leucine respectively. In rats 1–15 days after hypophysectomy, corticotropin, like dibutyryl cyclic AMP, induces an increase in protein E similar to that induced in control rats, even though both compounds no longer stimulate total protein synthesis. Corticotropin stimulation of protein E synthesis is mediated by cyclic AMP but not by corticosterone, since aminoglutethimide, a steroidogenic inhibitor, does not affect corticotropin stimulation, and dexamethasone alone has no effect. Actinomycin D, when injected in vivo 1h before or after corticotropin injection, prevents the effect of corticotropin on protein E synthesis, which is interpreted as evidence that mRNA synthesis is necessary for the stimulation of protein E synthesis. When injected more than 2h after corticotropin, actinomycin D does not prevent corticotropin stimulation of protein E synthesis, but completely blocks corticotropin stimulation of total protein synthesis. This is interpreted as meaning that, after stimulation of mRNA coding for protein E, corticotropin has no effect on the synthesis of protein E. On the other hand, corticotropin stimulation of protein E synthesis persists after hypophysectomy even though it no longer stimulates total protein synthesis. These data suggest that the factor(s) involved in the synthesis of protein E are more stable than those involved in total protein synthesis.

Stimulation of Insulin Release Is Uncoupled from Insulin Biosynthesis in Tumoral RINmSF Cells

Pancreas ◽  
1992 ◽  
Vol 7 (2) ◽  
pp. 245-250 ◽  
Author(s):  
Bernd Swarovsky ◽  
Matthias Eisenacher ◽  
Michael E. Trautmann ◽  
Rüdiger Göke ◽  
Rudolf Arnold
Keyword(s):  
Insulin Release ◽  
Insulin Biosynthesis ◽  
Stimulation Of

Effects of cyclic AMP on DNA replication and protein biosynthesis in fetal rat islets of Langerhans maintained in tissue culture

1982 ◽  
Vol 2 (11) ◽  
pp. 867-876 ◽  
Author(s):  
I. Swenne
Keyword(s):  
Tissue Culture ◽  
Dna Replication ◽  
Cyclic Amp ◽  
Islets Of Langerhans ◽  
Protein Biosynthesis ◽  
Insulin Production ◽  
Rat Islets ◽  
Fetal Rat ◽  
Rat Islets Of Langerhans ◽  
Stimulation Of

The regulatory role of cyclic AMP (cAMP) in the growth and insulin production of the islet organ in vitro has been investigated. The effects of dibutyryl cyclic AMP (dbcAMP), theophylline, and 3-isobutyl-1-methylxanthine (IBMX) on DNA replication and on the biosynthesis of RNA and insulin in fetal rat islets of Langerhans maintained in tissue culture have been studied. Raising the glucose concentration from 2.7 mM to 16.7 mM caused a two-fold increase in DNA replication. Both dbcAMP and theophylline markedly inhibited the DNA replication at all glucose Concentrations studied. Low concentrations of IBMX stimulated DNA synthesis. However, at higher concentrations of this drug, known to considerably increase the islet cAMP levels, a marked inhibition of islet DNA replication was observed. Both (pro)insulin and total protein biosynthesis were stimulated by glucose, whereas dbcAMP stimulated only the (pro)insulin biosynthesis. Since glucose is known to raise islet intracellular levels of cAMP, which is known to be an inhibitor of cellular proliferation, the observed glucose stimulation of both islet-cell DNA replication and insulin production appeared conflicting. It is suggested that this dual effect of glucose may depend on a stimulation of proliferation in a limited pool of islet cells which may not exhibit an increase in cAMP.

scholarly journals Mechanisms of the stimulation of insulin release by oxytocin in normal mouse islets

1991 ◽  
Vol 276 (1) ◽  
pp. 169-174 ◽  
Author(s):  
Z Y Gao ◽  
G Drews ◽  
J C Henquin
Keyword(s):  
B Cells ◽  
Cyclic Amp ◽  
Insulin Release ◽  
Islet Cells ◽  
Inositol Phosphate ◽  
Resting Potential ◽  
Phosphoinositide Metabolism ◽  
Mouse Islets ◽  
45Ca Efflux ◽  
Stimulation Of

Oxytocin (OT) produced a dose-dependent increase in somatostatin, glucagon and insulin release by isolated mouse islets. A small effect on somatostatin release was observed with 0.1 nM-OT, but 1-10 nM-OT was required to affect A- and B- cells significantly. The effects of OT on somatostatin and glucagon release were similar in the presence of 3 mM- and 10 mM-glucose. No change in insulin release was produced by OT in 3 mM-glucose, but a stimulation was still observed in the presence of a maximally effective concentration of glucose (30 mM). The increase in insulin release produced by OT (in 15 mM-glucose) was accompanied by small accelerations of 86Rb and 45Ca efflux from islet cells. Omission of extracellular Ca2+ accentuated the effect of OT on 86Rb efflux, attenuated that on 45Ca efflux, and abolished that on release. OT never inhibited 86Rb efflux. It did not affect the resting potential of B-cells, but slightly increased the Ca2(+)-dependent electrical activity induced by 15 mM-glucose. OT did not affect cyclic AMP levels, but increased inositol phosphate levels in islet cells. It is suggested that the amplification of glucose-induced insulin release that OT produces is due to a stimulation of phosphoinositide metabolism, and presumably an activation of protein kinase C, rather than to a change in cyclic AMP levels or a direct action on the membrane potential. Since OT is present in the pancreas, it is possible that it exerts a neuropeptidergic control of the islet function.

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