Biopolym. Cell. 1993; 9(1):39-44.
Gene-Engineering Biotechnology
Transplantation of human preproinsulin gene into the insuline dependent diabetic and normal rats
1Titok T. G., 1Kostetsky I. E., 1Tchaikovskaya T. L., 1Varzanova I. S., 1Kochubey T. P., 1Lukash L. L., 1Kordium V. A.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680

Abstract

The encapsulated into liposomes recombinant plasmid DNAs carrying the human preproinsulin gene sequences (pAINS and GINS) were injected into the liver and the intraperitoneum of streptozotocin and autoimmune insulin-dependent diabete rats. The injection of plasmids decreased glucose concentration in serum of streptozotocin diabetic rats. Maximal effect was detected in 8–10 hr after injection and glucose concentration returned in 24 h to initial levels. The injected diabetic BB rats not display a similar response. There was noticeable immunoreactive product concentration variation in raf blood serum after injection. Possible endocrine and immunological mechanisms of this.effect are discussed.

References

[1] Keller G, Paige C, Gilboa E, Wagner EF. Expression of a foreign gene in myeloid and lymphoid cells derived from multipotent haematopoietic precursors. Nature. 1985 Nov 14-20;318(6042):149-54.
[2] Garver RI Jr, Chytil A, Courtney M, Crystal RG. Clonal gene therapy: transplanted mouse fibroblast clones express human alpha 1-antitrypsin gene in vivo. Science. 1987;237(4816):762-4.
[3] Louis DSt, Verma IM. Whole animal gene transfer. Gene transfer vectors mammalian cells: Banbury conf. Cold Spring Harbor (New York, October 14-17, 1987). New York, 1987: 94-102.
[4] Selden RF, Skoskiewicz MJ, Howie KB, Russell PS, Goodman HM. Implantation of genetically engineered fibroblasts into mice: implications for gene therapy. Science. 1987;236(4802):714-8.
[5] Briand P. Animal models of gene therapy. J Genet Hum. 1989;37(4-5):289-97.
[6] Nicolau C, Le Pape A, Soriano P, Fargette F, Juhel MF. In vivo expression of rat insulin after intravenous administration of the liposome-entrapped gene for rat insulin I. Proc Natl Acad Sci U S A. 1983;80(4):1068-72.
[7] Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL. Direct gene transfer into mouse muscle in vivo. Science. 1990;247(4949 Pt 1):1465-8.
[8] Lukash LL, Neborachko LN, Podolskaya SV, Varzanova IS, Titok TG, Buzhievskaya TI, Kordyum VA. Expression of exogenic human insulin gene in subcultures and clones of cultivated fibroblasts. Doklady Akad Nauk Ukr SSR. Ser B. 1989;(8):71-4.
[9] Titok TG, Kostetsky IE, Chaikovskaya TL, Kochubej TP, Zharova LG, Kirilenko SD, Melnik IM, Silvanskaya EM, Buzhievskaya TI, Kordium VA. Transfer of human preproinsulin gene into streptozotocin diabetic rats. Biopolym Cell. 1990; 6(2):76-80.
[10] King GL, Kaher CR. Effect of insulin on growth in vivo and cell in culture. In: Control of animal cells proliferation. Eds. A. L. Boyton, H. L. Leffert. New York : Acad, press, 1985. Vol. 1: 201-49.
[11] Decker K. Biologically active products of stimulated liver macrophages (Kupffer cells). Eur J Biochem. 1990;192(2):245-61. Review.
[12] del Rey A, Besedovsky H. Antidiabetic effects of interleukin 1. Proc Natl Acad Sci U S A. 1989;86(15):5943-7.
[13] Lyashenko VA, Drozhennikov VA, Molotkovskaya IM. Mechanisms of immune cells activation. Moscow, Medicine, 1988; 239 p.
[14] Margolis LB, Bergelson LD Liposomes and their interaction with the cells. Moscow: Nauka, 1986. 240 p.
[15] Nakano K, Mordes JP, Handler ES, Greiner DL, Rossini AA. Role of host immune system in BB/Wor rat. Predisposition to diabetes resides in bone marrow. Diabetes. 1988;37(5):520-5.
[16] Poltorak VV, Blokh KO. Autoimmune genesis of the insulin dependent diabetes mellitus at the BB rat model. Immunologiya. 1989; 3: 5-10.
[17] Bendtzen K, Buschard K, Diamant M, Horn T, Svenson M. Possible role of IL-1, TNF-alpha, and IL-6 in insulin-dependent diabetes mellitus and autoimmune thyroid disease. Thyroid Cell Group. Lymphokine Res. 1989 Fall;8(3):335-40.
[18] Prud'homme GJ, Lapchak PH, Parfrey NA, Colle E, Guttmann RD. Autoimmunity-prone BB rats lack functional cytotoxic T cells. Cell Immunol. 1988;114(1):198-208.