Reprogramming Cells to Make Insulin

McKimpson, Wendy M.; Accili, Domenico

doi:10.1210/js.2019-00040

Cited by 19 publications

(12 citation statements)

References 116 publications

(109 reference statements)

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“…There have been several attempts in the past to convert non-endocrine cells into insulin-producing cells [ 38 , 39 ], including viral-mediated expression of transcription factors in human hepatocytes [ 38 ], mouse gastrointestinal cells [ 40 ], and acinar cells [ 41 , 42 ]. Ectopic PDX1 expression in adult human liver cells induced the development of functional insulin-producing cells; these cells when transplanted under the renal capsule of diabetic, immunodeficient mice ameliorated hyperglycemia [ 43 ].…”

Section: Non-endocrine Cells As a Source Of New β Cellsmentioning

confidence: 99%

Alpha-to-beta cell trans-differentiation for treatment of diabetes

Saleh

Gittes

Prasadan

2021

Biochemical Society Transactions

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Diabetes mellitus is a significant cause of morbidity and mortality in the United States and worldwide. According to the CDC, in 2017, ∼34.2 million of the American population had diabetes. Also, in 2017, diabetes was the seventh leading cause of death and has become the number one biomedical financial burden in the United States. Insulin replacement therapy and medications that increase insulin secretion and improve insulin sensitivity are the main therapies used to treat diabetes. Unfortunately, there is currently no radical cure for the different types of diabetes. Loss of β cell mass is the end result that leads to both type 1 and type 2 diabetes. In the past decade, there has been an increased effort to develop therapeutic strategies to replace the lost β cell mass and restore insulin secretion. α cells have recently become an attractive target for replacing the lost β cell mass, which could eventually be a potential strategy to cure diabetes. This review highlights the advantages of using α cells as a source for generating new β cells, the various investigative approaches to convert α cells into insulin-producing cells, and the future prospects and problems of this promising diabetes therapeutic strategy.

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Section: Non-endocrine Cells As a Source Of New β Cellsmentioning

confidence: 99%

Alpha-to-beta cell trans-differentiation for treatment of diabetes

Saleh

Gittes

Prasadan

2021

Biochemical Society Transactions

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“…Other approaches include the induction of insulin-producing β cells or β-like cells in vitro and in vivo. Eventually, several methods were developed to generate or reprogram endodermal cells into β cells or β-like cells in vitro and in vivo [21,22].…”

Section: Regenerative Medicinementioning

confidence: 99%

State-of-the-Art Technology of Model Organisms for Current Human Medicine

et al. 2020

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Since the 1980s, molecular biology has been used to investigate medical field mechanisms that still require the use of crude biological materials in order to achieve their necessary goals. Transcription factor-induced pluripotent stem cells are used in regenerative medicine to screen drugs and to support lost tissues. However, these cells insufficiently reconstruct whole organs and require various intact cells, such as damaged livers and diabetic pancreases. For efficient gene transfer in medical use, virally mediated gene transfers are used, although immunogenic issues are investigated. To obtain efficient detective and diagnostic power in intractable diseases, biological tools such as roundworms and zebrafish have been found to be useful for high-throughput screening (HST) and diagnosis. Taken together, this biological approach will help to fill the gaps between medical needs and novel innovations in the field of medicine.

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“…An attractive alternative is in vivo generation of insulin-producing, glucose-responsive β-like cells from other cell types. We and others have demonstrated the feasibility of this approach by reprogramming enteroendocrine cells (EECs) (7). Inhibition of Foxo1 by genetic ablation induced the formation of β-like cells in vivo in streptozotocin-diabetic mice, restoring glucose control (8), and inhibition by shRNA or a dominant negative mutation induced β-like cell conversion in human iPS-derived gut organoids in vitro (9).…”

Section: Introductionmentioning

confidence: 99%

Single-agent Foxo1 inhibition normalizes glycemia and induces gut β-like cells in streptozotocin-diabetic mice

Lee¹,

Nie²,

Diaz

et al. 2022

Preprint

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Insulin treatment remains the sole effective intervention for Type 1 Diabetes. Here, we investigated the therapeutic potential of converting intestinal epithelial cells to insulin-producing, glucose-responsive β-like cells by targeted inhibition of Foxo1. We have shown that this can be achieved by genetic ablation in gut Neurogenin3 progenitors, adenoviral or shRNA-mediated inhibition in human gut organoids, and chemical inhibition in Akita mice, a model of insulin-deficient diabetes. In the present study, we provide evidence that two novel Foxo1 inhibitors, FBT432 and FBT374 have glucose-lowering and gut β-like cell-inducing properties in mice rendered insulin-deficient by administration of streptozotocin. FBT432 is also highly effective in combination with a Notch inhibitor in this model. The data add to a growing body of evidence suggesting that Foxo1 inhibition be pursued as an alternative treatment to insulin administration in diabetes.

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Reprogramming Cells to Make Insulin

Cited by 19 publications

References 116 publications

Alpha-to-beta cell trans-differentiation for treatment of diabetes

Alpha-to-beta cell trans-differentiation for treatment of diabetes

State-of-the-Art Technology of Model Organisms for Current Human Medicine

Single-agent Foxo1 inhibition normalizes glycemia and induces gut β-like cells in streptozotocin-diabetic mice

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