Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1994-06-23
1998-04-28
Hutzell, Paula K.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
435 691, 435 703, C12P 2102, C12N 1500
Patent
active
057443270
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates generally to the preparation, culture and use of engineered cells having the ability to secrete insulin in response to glucose, to methods for the detection of diabetes-associated antigens, and to methods employing engineered cells in the production of human insulin for use in, for example, type I diabetes mellitus. In particular aspects, the present invention relates to the growth of engineered cells in liquid culture and the increase in glucose-mediated insulin release by such cells.
DESCRIPTION OF THE RELATED ART
Insulin-dependent diabetes mellitus (IDDM, also known as Juvenile-onset, or Type I diabetes) represents approximately 15% of all human diabetes. IDDM is distinct from non-insulin dependent diabetes (NIDDM) in that only IDDM involves specific destruction of the insulin producing .beta.-cells of the islets of Langerhans in the pancreas. The destruction of .beta.-cells in IDDM appears to be a result of specific autoimmune attack, in which the patient's own immune system recognizes and destroys the .beta.-cells, but not the surrounding .alpha. (glucagon producing) or .delta. (somatostatin producing) cells that comprise the islet.
The precise events involved in .beta.-cell recognition and destruction in IDDM are currently unknown, but involve both the "cellular" and "humoral" components of the immune system. In IDDM, islet .beta.-cell destruction is ultimately the result of cellular mechanisms, in which "killer T-cells" destroy .beta. cells which are erroneously perceived as foreign or harmful. The humoral component of the immune system, comprised of the antibody-producing B cells, is also inappropriately active in IDDM patients, who have serum antibodies against various .beta. cell proteins. Antibodies directed against intracellular proteins probably arise as a consequence of .beta.-cell damage which releases proteins previously "unseen" by the immune system. However, the appearance of antibodies against several cell surface epitopes such as insulin, proinsulin, the "38kD protein", immunoglobulins, the 65kD heat shock protein and the 64kD and 67kD forms of glutamic acid decarboxylase (GABA) are believed to be linked to the onset of IDDM (Lernmark, 1982). Antibodies in diabetic sera may also interact with the islet GLUT-2 glucose transporter (Johnson, et al., 1990c).
A progressive loss of .beta.-cell function is observed in the early stages of NIDDM and IDDM, even prior to the autoimmune .beta. cell destruction in IDDM. The specific function of glucose-stimulated insulin release is lost in islets of diabetic patients, despite the fact that such islets continue to respond to non-glucose secretagogues such as amino acids and isoproterenol (Srikanta, et al., 1983).
The participation of the pancreatic islets of Langerhans in fuel homeostasis is mediated in large part by their ability to respond to changes in circulating levels of key metabolic fuels by secreting peptide hormones. Accordingly, insulin secretion from islet .beta.-cells is stimulated by amino acids, three-carbon sugars such as glyceraldehyde, and most prominently, by glucose. The capacity of normal islet .beta.-cells to "sense" a rise in blood glucose concentration, and to respond to elevated levels of glucose (as occurs following ingestion of a carbohydrate containing meal) by secreting insulin is critical to control of blood glucose levels. Increased insulin secretion in response to a glucose load prevents chronic hyperglycemia in normal individuals by stimulating glucose uptake into peripheral tissues, particularly muscle and adipose tissue.
Mature insulin consists of two polypeptide chains, A and B, joined in a specific manner. However, the initial protein product of the insulin gene in .beta.-cells is not insulin, but preproinsulin. This precursor differs from mature insulin in two ways. Firstly, it has a so-called N-terminal "signal" or "pre" sequence which directs the polypeptide to the rough endoplasmic reticulum, where it is proteolytically processed. The product, proinsulin
REFERENCES:
patent: 4195125 (1980-03-01), Wacker
patent: 5073491 (1991-12-01), Familletti
patent: 5175085 (1992-12-01), Johnson et al.
patent: 5427940 (1995-06-01), Newgard
Cullen et al., Endocrinology, vol. 125, pp. 1774-1782, 1989.
Ullrich et al. JRC, vol. 259, pp. 4111-4115, 1984.
Hassid, American J. Physiology, vol. 244, pp. C369-C376, 1983.
Becker, et al., "Use of Recombinant Adenovirus Vectors for High-Efficiency Gene Transfer into the Islets of Langerhans," abstract No. 29, Diabetes, Abstract book, 53rd Annual Meeting, Jun. 12-15, 1993, Las Vegas, NV.
Ferber, et al., "Molecular Strategies for the Treatment of Diabetes," Transplant. Proc., 26(2):363-365 (Apr. 1994).
Mastrangeli, et al., "Diversity of Airway Epithelial Cell Targets for In Vivo Recombinant Adenovirus-mediated Gene Transfer," J. Clin. Invest., 91(1):225-234 (1993).
Newgard, C., "Cellular Engineering for the Treatment of Metabolic Disorders: Prospects for Therapy in Diabetes," Biotechnology, 10:1112-1120 (Oct. 1992).
Shih, et al., "An Adenoviral Vector System for Functional Identification of Nuclear Receptor Ligands," Mol. Endo., 5(2):300-309 (1991).
Chen et al., "Regulation of .beta.-cell glucose transporter gene expression," Proc. Natl. Acad. Sci., 87:4088-4092, 1990.
Shibasaki et al., "Overexpression of glucose transporter modulates insulin biosynthesis in insulin producing cell line," FEBS Lett., 270(1,2):105-107, 1990.
Johnson et al., "Underexpression of .beta. Cell High Km Glucose Transporters in Noninsulin-Dependent Diabetes," Science, 250:546-549, 1990.
Orci et al., "Evidence that down-regulation of .beta.-cell glucose transporters in non-insulin-dependent diabetes may be the cause of diabetic hyperglycemia," Proc. Natl. Acad. Sci., 87:9953-9957, 1990.
Johnson et al., "The High Km Glucose Transporter of Islets of Langerhans Is Functionally Similar to the Low Affinity Transporter of Liver and Has an Identical Primary Sequence," J. Biol. Chem., 265(12):6548-6551, 1990.
Newgard et al., "Glucokinase and glucose transporter expression in liver and islets: implications for control of glucose homeostasis," Biochem. Soc. Trans., 18:851-853, 1990.
Newgard et al., "Analysis of glucokinase and glucose transporter gene products in islet, liver, and anterior pituitary cells and their role in glucose sensing," FASEB J. 4(7):A2008, Abstract # 1827.
Matsutani et al., "Polymorphisms of GLUT2 and GLUT4 Genes," Diabetes, 39:1534-1542, 1990.
B.ae butted.kkeskov et al., "Antibodies to a 64,000 M.sub.r Human Islet Cell Antigen Precede the Clinical Onset of Insulin-dependent Diabetes," J. Clin. Invest., 79:926-934, 1987.
B.ae butted.kkeskov et al., "Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase," Nature, 347:151-156, 1990.
Kaufman et al., "Brain Glutamate Decarboxylase Cloned in .lambda.gt-11: Fusion Protein Produces .gamma.-Aminobutyric Acid," Science, 232:1138-1140, 1986.
Johnson et al., "Inhibition of glucose transport into rat islet cells by immunoglobulins from patients with new-onset insulin-dependent diabetes mellitus," N. Engl. J. Med., 322(10):653-659.
Permutt et al., "Cloning and functional expression of a human pancreatic islet glucose-transporter cDNA," Proc. Natl. Acad. Sci., 86:8688-8692, 1989.
Iynedjian et al., "Differential expression and regulation of the glucokinase gene in liver and islets of Langerhans," Proc. Natl. Acad. Sci., 86:7838-7842, 1989.
Maclaren, N.K., "Perspectives in Diabetes: How, When, and Why to Predict IDDM," Diabetes, 37:1591-1593, 1988.
Thorens et al., "Cloning and Functional Expression in Bacteria of a Novel Glucose Transporter Present in Liver, Intestine, Kidney, and .beta.-Pancreatic Islet Cells," Cell, 55:281-290, 1988.
Selden et al., "Regulation of insulin-gene expression: Implications for gene therapy," N. Engl. J. Med., 317(17):1067-1076, 1987.
Kuwajima et al., "The glucose-phosphorylating capacity of liver as measured by three independent assays," J. Biol. Chem., 261(19):8849
Board of Regents , The University of Texas System
Gucker Stephen
Hutzell Paula K.
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