Abstract
To extend previous observations on the mechanisms of translational regulation of insulin biosynthesis [Welsh, Scherberg, Gilmore & Steiner (1986) Biochem. J. 235, 459-467], we have now compared the intracellular distributions of insulin mRNA after stimulation of insulin biosynthesis by glucose, leucine or theophylline. In comparison with low glucose (3.3 mM) only, the presence of 10 mM-leucine + 3.3 mM-glucose resulted in the transfer of insulin mRNA from the pool of the uninitiated mRNA to the free polysome/monosome fraction and an increase in the amount of insulin mRNA associated with the microsomal fraction. Islets exposed to 5 mM-theophylline + 3.3 mM-glucose also showed a decreased content of uninitiated insulin mRNA in the cytosol, but these islets showed no increase in insulin mRNA in the microsomal fraction. These results suggest that leucine, a nutrient stimulant of insulin biosynthesis, acts essentially by the same mechanisms as those of glucose, whereas theophylline acts only to stimulate initiation rates.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andersson A., Höiriis-Nielsen J., Borg L. A. Effects of L-leucine on the insulin production, oxidative metabolism and mitochondrial ultrastructure of isolated mouse pancreatic islets in tissue culture. Diabetologia. 1977 Jan;13(1):59–69. doi: 10.1007/BF00996329. [DOI] [PubMed] [Google Scholar]
- Ashcroft S. J., Bunce J., Lowry M., Hansen S. E., Hedeskov C. J. The effect of sugars on (pro)insulin biosynthesis. Biochem J. 1978 Aug 15;174(2):517–526. doi: 10.1042/bj1740517. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ayuso M. S., Vega P., Manchón C. G., Parrilla R. Interrelation between gluconeogenesis and hepatic protein synthesis. Biochim Biophys Acta. 1986 Aug 6;883(1):33–40. doi: 10.1016/0304-4165(86)90131-5. [DOI] [PubMed] [Google Scholar]
- Bag J., Sarkar S. Cytoplasmic nonpolysomal messenger ribonucleoprotein containing actin messenger RNA in chicken embryonic muscles. Biochemistry. 1975 Aug 26;14(17):3800–3807. doi: 10.1021/bi00688a012. [DOI] [PubMed] [Google Scholar]
- Burkhard S. J., Traugh J. A. Changes in ribosome function by cAMP-dependent and cAMP-independent phosphorylation of ribosomal protein S6. J Biol Chem. 1983 Nov 25;258(22):14003–14008. [PubMed] [Google Scholar]
- Chan S. J., Noyes B. E., Agarwal K. L., Steiner D. F. Construction and selection of recombinant plasmids containing full-length complementary DNAs corresponding to rat insulins I and II. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5036–5040. doi: 10.1073/pnas.76.10.5036. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Christie M. R., Ashcroft S. J. Cyclic AMP-dependent protein phosphorylation and insulin secretion in intact islets of Langerhans. Biochem J. 1984 Feb 15;218(1):87–99. doi: 10.1042/bj2180087. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Christie M. R., Ashcroft S. J. Substrates for cyclic AMP-dependent protein kinase in islets of Langerhans. Studies with forskolin and catalytic subunit. Biochem J. 1985 May 1;227(3):727–736. doi: 10.1042/bj2270727. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gilmore R., Blobel G. Transient involvement of signal recognition particle and its receptor in the microsomal membrane prior to protein translocation. Cell. 1983 Dec;35(3 Pt 2):677–685. doi: 10.1016/0092-8674(83)90100-9. [DOI] [PubMed] [Google Scholar]
- Howell S. L., Taylor K. W. Potassium ions and the secretion of insulin by islets of Langerhans incubated in vitro. Biochem J. 1968 Jun;108(1):17–24. doi: 10.1042/bj1080017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hunt T., Herbert P., Campbell E. A., Delidakis C., Jackson R. J. The use of affinity chromatography on 2'5' ADP-sepharose reveals a requirement for NADPH, thioredoxin and thioredoxin reductase for the maintenance of high protein synthesis activity in rabbit reticulocyte lysates. Eur J Biochem. 1983 Mar 15;131(2):303–311. doi: 10.1111/j.1432-1033.1983.tb07263.x. [DOI] [PubMed] [Google Scholar]
- Hutton J. C., Malaisse W. J. Dynamics of O2 consumption in rat pancreatic islets. Diabetologia. 1980 May;18(5):395–405. doi: 10.1007/BF00276821. [DOI] [PubMed] [Google Scholar]
- Itoh N., Okamoto H. Translational control of proinsulin synthesis by glucose. Nature. 1980 Jan 3;283(5742):100–102. doi: 10.1038/283100a0. [DOI] [PubMed] [Google Scholar]
- Jackson R. J., Herbert P., Campbell E. A., Hunt T. The roles of sugar phosphates and thiol-reducing systems in the control of reticulocyte protein synthesis. Eur J Biochem. 1983 Mar 15;131(2):313–324. doi: 10.1111/j.1432-1033.1983.tb07264.x. [DOI] [PubMed] [Google Scholar]
- Jagus R., Safer B. Activity of eukaryotic initiation factor 2 is modified by processes distinct from phosphorylation. I. Activities of eukaryotic initiation factor 2 and eukaryotic initiation factor 2 alpha kinase in lysate gel filtered under different conditions. J Biol Chem. 1981 Feb 10;256(3):1317–1323. [PubMed] [Google Scholar]
- Lernmark A., Nathans A., Steiner D. F. Preparation and characterization of plasma membrane-enriched fractions from rat pancreatic islets. J Cell Biol. 1976 Nov;71(2):606–623. doi: 10.1083/jcb.71.2.606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malaisse W. J., Hutton J. C., Carpinelli A. R., Herchuelz A., Sener A. The stimulus-secretion coupling of amino acid-induced insulin release: metabolism and cationic effects of leucine. Diabetes. 1980 Jun;29(6):431–437. doi: 10.2337/diab.29.6.431. [DOI] [PubMed] [Google Scholar]
- Malaisse W. J., Pipeleers D. G., Levy J. The stimulus-secretion coupling of glucose-induced insulin release. XVI. A glucose-like and calcium-independent effect of cyclic AMP. Biochim Biophys Acta. 1974 Aug 7;362(1):121–128. doi: 10.1016/0304-4165(74)90033-6. [DOI] [PubMed] [Google Scholar]
- Meyer D. I., Krause E., Dobberstein B. Secretory protein translocation across membranes-the role of the "docking protein'. Nature. 1982 Jun 24;297(5868):647–650. doi: 10.1038/297647a0. [DOI] [PubMed] [Google Scholar]
- Nielsen J. H. Dissociation between insulin secretion and DNA synthesis in cultured pancreatic islets. Biomed Biochim Acta. 1985;44(1):161–166. [PubMed] [Google Scholar]
- Ramsey J. C., Steele W. J. A procedure for the quantitative recovery of homogeneous populations of undegraded free and bound polysomes from rat liver. Biochemistry. 1976 Apr 20;15(8):1704–1712. doi: 10.1021/bi00653a018. [DOI] [PubMed] [Google Scholar]
- Sandler S., Welsh M., Andersson A. Streptozotocin-induced impairment of islet B-cell metabolism and its prevention by a hydroxyl radical scavenger and inhibitors of poly(ADP-ribose) synthetase. Acta Pharmacol Toxicol (Copenh) 1983 Nov;53(5):392–400. doi: 10.1111/j.1600-0773.1983.tb03440.x. [DOI] [PubMed] [Google Scholar]
- Schatz H., Maier V., Hinz M., Nierle C., Pfeiffer E. F. Stimulation of H-3-leucine incorporation into the proinsulin and insulin fraction of isolated pancreatic mouse islets in the presence of glucagon, theophylline and cyclic AMP. Diabetes. 1973 Jun;22(6):433–441. doi: 10.2337/diab.22.6.433. [DOI] [PubMed] [Google Scholar]
- Sharp G. W. The adenylate cyclase-cyclic AMP system in islets of Langerhans and its role in the control of insulin release. Diabetologia. 1979 May;16(5):287–296. doi: 10.1007/BF01223617. [DOI] [PubMed] [Google Scholar]
- Suzuki H., Mukouyama E. B. Mechanism of stimulation of globin synthesis by adenosine-3',5'-monophosphate and guanosine 5'-triphosphate in a rabbit reticulocyte lysate system. J Biochem. 1985 May;97(5):1289–1300. doi: 10.1093/oxfordjournals.jbchem.a135180. [DOI] [PubMed] [Google Scholar]
- Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Welsh M., Hammer R. E., Brinster R. L., Steiner D. F. Stimulation of growth hormone synthesis by glucose in islets of Langerhans isolated from transgenic mice. J Biol Chem. 1986 Oct 5;261(28):12915–12917. [PubMed] [Google Scholar]
- Welsh M., Scherberg N., Gilmore R., Steiner D. F. Translational control of insulin biosynthesis. Evidence for regulation of elongation, initiation and signal-recognition-particle-mediated translational arrest by glucose. Biochem J. 1986 Apr 15;235(2):459–467. doi: 10.1042/bj2350459. [DOI] [PMC free article] [PubMed] [Google Scholar]
- White B. A., Bancroft F. C. Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. J Biol Chem. 1982 Aug 10;257(15):8569–8572. [PubMed] [Google Scholar]