Gene and cell-replacement therapy in the treatment of type 1 diabetes: how high must the standards be set?

Recent advances in molecular and cell biology may allow for the development of novel strategies for the treatment and cure of type 1 diabetes. In particular, it is now possible to envisage restoration of insulin secretion by gene or cell-replacement therapy. The beta-cell is, however, remarkably sophisticated, and many of the features of this highly differentiated secretory cell will have to be faithfully mimicked in surrogate cells. In particular, insulin is normally secreted in a well-regulated fashion in rapid response to the metabolic needs of the individual and most specifically (but not exclusively) to changes in circulating levels of glucose. Such regulated secretion will be indispensable in order to avoid both hyper- and hypoglycemic episodes and depends on the ability of cells to store insulin in secretory granules before exocytosis in response to physiological stimuli. Furthermore, any newly created insulin-secreting cell will have to be able to adapt to alterations in insulin requirements that accompany changes with exercise, body weight, and aging. Fine tuning of insulin secretion over the longer term will also be important to avoid "clinical shifting" that could be caused by over-insulinization, including increased adiposity and cardiovascular disease. Finally, it will be necessary to ensure that newly created or implanted (surrogate) beta-cells are protected in some way from recognition by the immune system and in particular from autoimmune destruction.

[1]  J. Itskovitz‐Eldor,et al.  Insulin production by human embryonic stem cells. , 2001, Diabetes.

[2]  B. Wicksteed,et al.  Cooperativity between the Preproinsulin mRNA Untranslated Regions Is Necessary for Glucose-stimulated Translation* , 2001, The Journal of Biological Chemistry.

[3]  B. Topp,et al.  Beta-cell mass dynamics in Zucker diabetic fatty rats. Rosiglitazone prevents the rise in net cell death. , 2001, Diabetes.

[4]  R. McKay,et al.  Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets , 2001, Science.

[5]  J F Elliott,et al.  Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. , 2001, Diabetes.

[6]  F. Levine,et al.  Gene therapy for diabetes. , 2001, Frontiers in bioscience : a journal and virtual library.

[7]  D. Drucker,et al.  Minireview: the glucagon-like peptides. , 2001, Endocrinology.

[8]  J. Bryan,et al.  Of mice and men: K(ATP) channels and insulin secretion. , 2001, Recent progress in hormone research.

[9]  D. Kendall,et al.  Prevention of diabetes for up to 13 years by autoislet transplantation after pancreatectomy for chronic pancreatitis. , 2001, Diabetes.

[10]  G. Korbutt,et al.  Glucose-dependent insulin release from genetically engineered K cells. , 2000, Science.

[11]  Hyun Chul Lee,et al.  Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue , 2000, Nature.

[12]  J. Henquin,et al.  Triggering and amplifying pathways of regulation of insulin secretion by glucose. , 2000, Diabetes.

[13]  F. Bertuzzi,et al.  Development and Characterization of Pituitary GH3 Cell Clones Stably Transfected with a Human Proinsulin cDNA , 2000, Cell transplantation.

[14]  M. Meseck,et al.  Glucose-stimulated and self-limiting insulin production by glucose 6-phosphatase promoter driven insulin expression in hepatoma cells , 2000, Gene Therapy.

[15]  M. Prentki,et al.  Metabolic control of -cell function , 2000 .

[16]  P. Halban,et al.  Trafficking/sorting and granule biogenesis in the beta-cell. , 2000, Seminars in cell & developmental biology.

[17]  M. German,et al.  Regulation of insulin gene transcription. , 2000, Seminars in cell & developmental biology.

[18]  J. Hutton,et al.  Translational regulation of proinsulin biosynthesis and proinsulin conversion in the pancreatic beta-cell. , 2000, Seminars in cell & developmental biology.

[19]  E. Ryan,et al.  Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. , 2000, The New England journal of medicine.

[20]  S. Bonner-Weir,et al.  In vitro cultivation of human islets from expanded ductal tissue. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[21]  M. Prentki,et al.  Acute Stimulation with Long Chain Acyl-CoA Enhances Exocytosis in Insulin-secreting Cells (HIT T-15 and NMRI β-Cells)* , 2000, The Journal of Biological Chemistry.

[22]  M. Rewers,et al.  Early expression of antiinsulin autoantibodies of humans and the NOD mouse: evidence for early determination of subsequent diabetes. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[23]  L. Phillips,et al.  Glucose regulated production of human insulin in rat hepatocytes , 2000, Gene Therapy.

[24]  M. Prentki,et al.  Metabolic control of beta-cell function. , 2000, Seminars in cell & developmental biology.

[25]  B. AhrØn,et al.  Autonomic regulation of islet hormone secretion ± Implications for health and disease , 2000 .

[26]  C. Wollheim,et al.  Overexpression of monocarboxylate transporter and lactate dehydrogenase alters insulin secretory responses to pyruvate and lactate in beta cells. , 1999, The Journal of clinical investigation.

[27]  M. Atkinson,et al.  The NOD mouse model of type 1 diabetes: As good as it gets? , 1999, Nature Medicine.

[28]  M. Nauck.  Is glucagon-like peptide 1 an incretin hormone? , 1999, Diabetologia.

[29]  D. Bruttomesso,et al.  Restoration of early rise in plasma insulin levels improves the glucose tolerance of type 2 diabetic patients. , 1999, Diabetes.

[30]  K. Docherty,et al.  Prospects for insulin delivery by ex-vivo somatic cell gene therapy , 1999, Journal of Molecular Medicine.

[31]  S. Efrat.  Prospects for gene therapy of insulin-dependent diabetes mellitus , 1998, Diabetologia.

[32]  P A Cleary,et al.  Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure: results from the DCCT. Diabetes Control and Complications Trial. , 1998, JAMA.

[33]  K. Salmela,et al.  Implantation of standardized beta-cell grafts in a liver segment of IDDM patients: graft and recipient characteristics in two cases of insulin-independence under maintenance immunosuppression for prior kidney graft , 1998, Diabetologia.

[34]  N. Seidah,et al.  Proprotein Convertases , 2011, Methods in Molecular Biology.

[35]  P. Halban,et al.  Release of Incompletely Processed Proinsulin Is the Cause of the Disproportionate Proinsulinemia of NIDDM , 1997, Diabetes.

[36]  A. Simpson,et al.  Gene therapy of diabetes: glucose-stimulated insulin secretion in a human hepatoma cell line (HEP G2ins/g) , 1997, Gene Therapy.

[37]  R. Gruessner,et al.  Tacrolimus in pancreas transplantation: a multicenter analysis. Tacrolimus Pancreas Transplant Study Group. , 1997, Clinical transplantation.

[38]  M. Prentki,et al.  Metabolic Fate of Glucose in Purified Islet Cells , 1997, The Journal of Biological Chemistry.

[39]  C. Newgard,et al.  Engineered cell lines for insulin replacement in diabetes: current status and future prospects , 1997, Diabetologia.

[40]  P. Muzzin,et al.  Hepatic insulin gene expression as treatment for type 1 diabetes mellitus in rats. , 1997, Molecular endocrinology.

[41]  M. Hammami.  Diabetes Mellitus: A Fundamental and Clinical Text , 1997 .

[42]  R N Bergman,et al.  Role of Glucose Effectiveness in the Determination of Glucose Tolerance , 1996, Diabetes Care.

[43]  K. Matsumoto,et al.  High-dose but not low-dose dexamethasone impairs glucose tolerance by inducing compensatory failure of pancreatic beta-cells in normal men. , 1996, The Journal of clinical endocrinology and metabolism.

[44]  D. Sutherland,et al.  Use of FK 506 in pancreas transplantation. , 1996, Transplant international : official journal of the European Society for Organ Transplantation.

[45]  B. Göke,et al.  Cell and molecular biology of the incretin hormones glucagon-like peptide-I and glucose-dependent insulin releasing polypeptide. , 1995, Endocrine reviews.

[46]  C. Newgard,et al.  Metabolic coupling factors in pancreatic beta-cell signal transduction. , 1995, Annual review of biochemistry.

[47]  R N Bergman,et al.  The Contribution of Insulin-Dependent and Insulin-Independent Glucose Uptake to Intravenous Glucose Tolerance in Healthy Human Subjects , 1994, Diabetes.

[48]  F. Bosch,et al.  Regulated expression of human insulin in the liver of transgenic mice corrects diabetic alterations , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[49]  P. Halban,et al.  Sorting and processing of secretory proteins. , 1994, The Biochemical journal.

[50]  M. Sliwkowski,et al.  Genetically engineered proinsulin constitutively processed and secreted as mature, active insulin. , 1994, The Journal of biological chemistry.

[51]  R. Bergman,et al.  Quantification of the Relationship Between Insulin Sensitivity and β-Cell Function in Human Subjects: Evidence for a Hyperbolic Function , 1993, Diabetes.

[52]  B. Sobel,et al.  Stimulation by Proinsulin of Expression of Plasminogen Activator Inhibitor Type-I in Endothelial Cells , 1992, Diabetes.

[53]  M. Cerqueira,et al.  Exercise training delineates the importance of B-cell dysfunction to the glucose intolerance of human aging. , 1992, The Journal of clinical endocrinology and metabolism.

[54]  M. Cerqueira,et al.  Effect of exercise on insulin action, glucose tolerance, and insulin secretion in aging. , 1990, The American journal of physiology.

[55]  G. Ward,et al.  Effects of Prolonged Pulsatile Hyperinsulinemia in Humans: Enhancement of Insulin Sensitivity , 1990, Diabetes.

[56]  D. Sutherland,et al.  Recurrence of Disease in Pancreas Transplants , 1989, Diabetes.

[57]  A. Baron,et al.  Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans. , 1988, The American journal of physiology.

[58]  E. Kraegen,et al.  Physiological Importance of Deficiency in Early Prandial Insulin Secretion in Non-Insulin-Dependent Diabetes , 1988, Diabetes.

[59]  P. Russell,et al.  Regulation of insulin-gene expression. Implications for gene therapy. , 1987 .

[60]  R. Henry,et al.  The effects of biosynthetic human proinsulin on carbohydrate metabolism in non-insulin-dependent diabetes mellitus. , 1987, The New England journal of medicine.

[61]  R. Boston,et al.  Metabolic Consequences of Prolonged Hyperinsulinemia in Humans: Evidence for Induction of Insulin Insensitivity , 1986, Diabetes.

[62]  R. Kelly.  Pathways of protein secretion in eukaryotes. , 1985, Science.

[63]  M. Löhr,et al.  Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited. , 1985, Survey and synthesis of pathology research.

[64]  J. Halter,et al.  Dexamethasone-induced insulin resistance enhances B cell responsiveness to glucose level in normal men. , 1984, The American journal of physiology.

[65]  J. Halter,et al.  Pathophysiology of Insulin Secretion in Non-insulin-dependent Diabetes Mellitus , 1984, Diabetes Care.

[66]  R. Kelly,et al.  Expressing a human proinsulin cDNA in a mouse ACTH-secreting cell. Intracellular storage, proteolytic processing, and secretion on stimulation , 1983, Cell.

[67]  H. Hendrickson.  Prevention of what? , 1983, Journal of the American Optometric Association.

[68]  Philippe Soriano,et al.  In vivo expression of rat insulin after intravenous administration of the liposome-entrapped gene for rat insulin I. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[69]  S. Kalhan,et al.  Inhibitory effect of prednisone on insulin secretion in man: model for duplication of blood glucose concentration. , 1975, The Journal of clinical endocrinology and metabolism.