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PMID: 6444726 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Plasminogen activator of islets of Langerhans: modulation by glucose and correlation with insulin production.

Virji MA, Vassalli JD, Estensen RD, Reich E

Abstract

Islets of Langerhans isolated from rat pancreas contain and secrete plasminogen activator (PA). Production of PA is increased up to 15-fold by culture in the presence of high concentrations of glucose, and the dose-response curves for the effect of glucose on secretion of PA and on insulin are superimposable. Alloxan, a diabetogenic agent that is selectively cytotoxic for beta cells, abolishes the PA response to glucose. Various agents and hormones that affect beta-cell function affect the secretion of PA in a manner parallel to their modulation of insulin secretion. These observations suggest that PA is produced by beta cells and that enzyme synthesis and secretion are regulated in concert with those of the hormone. The potential role of PA and of plasmin in the physiology of the islets is considered. In particular, because plasmin cleaves proinsulin to a product that is electrophoretically indistinguishable from insulin, it is suggested that the PA/plasmin system may play a part in the conversion of proinsulin to the active hormone.

MeSH Terms
Alloxan/pharmacology Animals Cells, Cultured Dose-Response Relationship, Drug Fibrinolysin/metabolism Glucose/pharmacology Insulin/metabolism Insulin Secretion Islets of Langerhans/drug effects,metabolism Male Molecular Weight Plasminogen Activators/biosynthesis Proinsulin/metabolism Rats
Chemicals
Insulin Alloxan Proinsulin Plasminogen Activators Fibrinolysin Glucose
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Virji M A
Vassalli J D
Estensen R D
Reich E
References (29)
29 references, click to expand
  1. Inhibitory effect of prednisone on insulin secretion in man: model for duplication of blood glucose concentration.
    J Clin Endocrinol Metab. 1975 Sep;41(3):600-10 PMID: 1159064
  2. The conversion of C'IS to C'1 esterase by plasmin and trypsin.
    J Exp Med. 1967 Feb 1;125(2):337-58 PMID: 4225264
  3. Proteolytic fragmentation of fibrinogen. I. Comparison of the fragmentation of human and bovine fibrinogen by trypsin or plasmin.
    Biochemistry. 1976 Nov 30;15(24):5372-81 PMID: 11813
  4. Carboxypeptidase B-like and trypsin-like activities in isolated rat pancreatic islets.
    Ciba Found Symp. 1976;41:183-95 PMID: 820528
  5. Studies on the secretion of newly synthesized proinsulin and insulin from isolated rat islets of Langerhans.
    J Clin Invest. 1972 Jun;51(6):1476-85 PMID: 4336941
  6. Size and charge distinctions between endogenous human plasma gastrin in peripheral blood and heptadecapeptide gastrins.
    Gastroenterology. 1970 May;58(5):609-15 PMID: 5444164
  7. A study of proteases and protease-inhibitor complexes in biological fluids.
    J Exp Med. 1978 Jul 1;148(1):223-34 PMID: 78958
  8. Somatostatin: hypothalamic inhibitor of the endocrine pancreas.
    Science. 1974 Apr 26;184(4135):482-4 PMID: 4594711
  9. Dynamic synthesis and release of insulin and proinsulin from perifused islets.
    Diabetes. 1973 May;22(5):354-60 PMID: 4573222
  10. Plasminogen: purification from human plasma by affinity chromatography.
    Science. 1970 Dec 4;170(3962):1095-6 PMID: 5475635
  11. Molecular weight analysis of oligopeptides by electrophoresis in polyacrylamide gel with sodium dodecyl sulfate.
    Anal Biochem. 1971 Feb;39(2):462-77 PMID: 4101989
  12. Biosynthesis of insulin and glucagon: a view of the current state of the art.
    Ciba Found Symp. 1976;41:7-30 PMID: 780079
  13. The effect of epinephrine and isoproterenol on insulin secretion and glucose utilization in isolated islets of Langerhans from mice.
    Acta Endocrinol (Copenh). 1977 Jan;84(1):105-14 PMID: 318787
  14. Cation requirements for insulin secretion in the isolated perfused pancreas.
    Diabetes. 1966 Dec;15(12):910-3 PMID: 5957483
  15. Insulin biosynthesis and secretion.
    Fed Proc. 1975 Jun;34(7):1549-55 PMID: 1093883
  16. Evidence for an inhibitor of insulin release in the pancreatic islets.
    Diabetologia. 1969 Feb;5(1):22-4 PMID: 4907150
  17. The biosynthesis of insulin and a probable precursor of insulin by a human islet cell adenoma.
    Proc Natl Acad Sci U S A. 1967 Feb;57(2):473-80 PMID: 16591494
  18. Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays.
    J Clin Endocrinol Metab. 1971 Nov;33(5):732-8 PMID: 5166455
  19. Electrophysiological evidence for the autoregulation of beta-cell secretion by insulin.
    Biochim Biophys Acta. 1977 Apr 27;497(2):408-14 PMID: 322725
  20. Method for the isolation of intact islets of Langerhans from the rat pancreas.
    Diabetes. 1967 Jan;16(1):35-9 PMID: 5333500
  21. Macrophage plasminogen activator: modulation of enzyme production by anti-inflammatory steroids, mitotic inhibitors, and cyclic nucleotides.
    Cell. 1976 Jun;8(2):271-81 PMID: 61067
  22. Less-understood aspects of the morphology of insulin secretion and binding.
    Recent Prog Horm Res. 1978;34:95-121 PMID: 366686
  23. Studies on the role of plasminogen activator in ovulation. In vitro response of granulosa cells to gonadotropins, cyclic nucleotides, and prostaglandins.
    J Biol Chem. 1976 Sep 25;251(18):5694-702 PMID: 965386
  24. Studies on the conversion of proinsulin to insulin. I. Conversion in vitro with trypsin and carboxypeptidase B.
    J Biol Chem. 1971 Nov 25;246(22):6786-91 PMID: 4942325
  25. Macrophage plasminogen activator: induction by concanavalin A and phorbol myristate acetate.
    Cell. 1977 Jul;11(3):695-705 PMID: 884740
  26. Recovery of surface membrane in anterior pituitary cells. Variations in traffic detected with anionic and cationic ferritin.
    J Cell Biol. 1978 Jun;77(3):R35-42 PMID: 567224
  27. "Big insulin": a new component of plasma insulin detected by immunoassay.
    Proc Natl Acad Sci U S A. 1968 Sep;61(1):138-45 PMID: 4301586
  28. Studies on insulin secretion in vitro from isolated islets of the rat pancreas.
    Endocrinology. 1968 Dec;83(6):1155-61 PMID: 4301830
  29. Size heterogeneity of immunoreactive human ACTH in plasma and in extracts of pituitary glands and ACTH-producing thymoma.
    Biochem Biophys Res Commun. 1971 Jul 16;44(2):439-45 PMID: 4334140
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1980-02-00
Pages
875-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC348384
Subset
IM
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