Glucose-stimulated and self-limiting insulin production by glucose 6-phosphatase promoter driven insulin expression in hepatoma cells

Chen, R; Meseck, Marcia; McEvoy, Robert; Woo, Savio L. C.

doi:10.1038/sj.gt.3301306

Cited by 62 publications

(35 citation statements)

References 45 publications

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“…Furthermore, one can exploit a number of hepatocyte gene promoters, which are sensitive to glucose, in order to engineer insulin transgenes to be glucose concentration-sensitive. Despite a number of promising approaches exploiting a number of glucose-regulated promoters, 126,128,129,131,[139][140][141][142][143][144] much more work is needed to make hepatocytes into fully surrogate b cells. The first feature that a hepatocyte is missing to properly act like a b-cell surrogate is the ability to respond to glucose in a sufficiently rapid fashion, as rapid as that characteristic of b cells.…”

Section: Insulin Replacement Strategiesmentioning

confidence: 99%

Gene- and cell-based therapeutics for type I diabetes mellitus

et al. 2003

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Section: Insulin Replacement Strategiesmentioning

confidence: 99%

Gene- and cell-based therapeutics for type I diabetes mellitus

et al. 2003

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“…36,37 Recently, several studies have attempted to engineer GSIS from hepatocytes by expressing insulin under the control of glucose responsive promoters, and have demonstrated that glucose regulated insulin secretion both in vitro and in diabetic animal models. 22,23 However, because the expression of insulin is controlled at the transcriptional level, both the rise of insulin and the clearance of this hormone in the circulation in response to glucose load are delayed by hours. 22 Alterations in insulin levels over a time course of hours rather than minutes is likely to lead to hypoglycemia and nonphysiologic insulin secretion.…”

Section: Insulin Secretion By Transduced Pituitary Cellsmentioning

confidence: 99%

“…[15][16][17][18] Engineering regulated insulin secretion in both b and non-b cells has mostly focused on recreating the signal transduction pathway of glucose. [19][20][21][22][23] Since the mechanisms in this pathway itself are not completely elucidated, engineering physiologically regulated insulin secretion has been difficult. In this report, we used an alternative approach to engineer regulated insulin secretion from nonb cells by introducing insulin and the GLP-1 receptor into neuroendocrine pituitary cells.…”

Section: Introductionmentioning

confidence: 99%

Engineering physiologically regulated insulin secretion in non-β cells by expressing glucagon-like peptide 1 receptor

Nicholson

et al. 2003

Gene Ther

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“…More often than not, insulin was released in a constitutive fashion, since regulated secretory cells were not used [see for example Chen et al (6) and Lee et al (7), to cite but two of the more recent studies], and several learned reviews have been written on the general theme of gene therapy for diabetes [for example (8 -11)]. The recent study showing glucose-regulated insulin secretion from a genetically engineered intestinal K-cell line is a refreshing exception in this regard, given the use of bona fide regulated secretory cells (12).…”

Section: Historical Perspectivementioning

confidence: 99%

Gene and Cell-Replacement Therapy in the Treatment of Type 1 Diabetes

et al. 2001

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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 ␤-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 overinsulinization, including increased adiposity and cardiovascular disease. Finally, it will be necessary to ensure that newly created or implanted (surrogate) ␤-cells are protected in some way from recognition by the immune system and in particular from autoimmune destruction. Diabetes 50:2181-2191, 2001 R ecent success in reversing type 1 diabetes by islet transplantation, as reported by the Edmonton group (1), has led to renewed optimism in the field. It is, however, quite apparent that human islets will never be available in sufficient numbers to satisfy the needs of all the patients in the world with diabetes. Furthermore, islet transplantation still requires long-term (and most likely life-long) immunosuppression. A seductive means of circumventing both of these obstacles would be by gene therapy or by cell-replacement therapy, two possible approaches for replacing endogenous insulin production that we have defined below. Our intention in this article is to place these two methods in as objective a setting as possible and to set minimal standards that we feel need to be met in order for them to be useful in a clinical setting. It is not our purpose to write a comprehensive review of the field, and we do not wish to take sides on any of the issues discussed. Our motivation is straightforward but strongly felt. We are particularly dismayed by the increasing number of papers, more often than not published in highly reputable (and on occasion in widely distributed) journals, claiming to be on track to a cure for diabetes by means of gene or cell therapy. These papers are often misleading, and those misled, given the attention such papers receive in the lay press and on television, are first and foremost patients with diabetes and their families. We encourage everyone to review all papers in this area of research with a critical ...

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Glucose-stimulated and self-limiting insulin production by glucose 6-phosphatase promoter driven insulin expression in hepatoma cells

Cited by 62 publications

References 45 publications

Gene- and cell-based therapeutics for type I diabetes mellitus

Gene- and cell-based therapeutics for type I diabetes mellitus

Engineering physiologically regulated insulin secretion in non-β cells by expressing glucagon-like peptide 1 receptor

Gene and Cell-Replacement Therapy in the Treatment of Type 1 Diabetes

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