Both type 1 and 2 diabetes are caused by inadequate insulin secretion, and in both diseases this can be ascribed in large part to loss of pancreatic ?-cells that produce insulin. Both diseases can be cured by replacement of pancreatic ?-cells by pancreas transplantation but this requires life-long immunosuppression and there are far fewer organ donors than people with diabetes. An alternative approach to restoring pancreatic ?-cells is to foster regeneration of ?-cells in the patient. Recent studies in mice have provided important insights into how ?-cells are formed and their number increased and maintained after birth. Complementary studies in humans are few because of the difficulty in obtaining appropriate material and the difficulty of undertaking lineage tracing studies in humans.

Public Health Relevance

Both type 1 and 2 diabetes are caused by inadequate insulin secretion; and in both diseases this can be ascribed in large part to loss of pancreatic ?-cells that produce insulin. Both diseases can be cured by replacement of pancreatic ?-cells by pancreas transplantation but this requires life-long immunosuppression and there are far fewer organ donors than people with diabetes. An alternative approach is to foster regeneration of ?-cells in the patient him/herself; and the basis of this grant is to explore an approach to that end

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK077967-06A1
Application #
8627827
Study Section
Special Emphasis Panel (ZRG1-EMNR-T (02))
Program Officer
Sato, Sheryl M
Project Start
2007-04-01
Project End
2017-06-30
Budget Start
2014-09-11
Budget End
2015-06-30
Support Year
6
Fiscal Year
2014
Total Cost
$334,950
Indirect Cost
$117,450
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Costes, Safia; Langen, Ralf; Gurlo, Tatyana et al. (2013) ?-Cell failure in type 2 diabetes: a case of asking too much of too few? Diabetes 62:327-35
Butler, Peter C; Elashoff, Michael; Elashoff, Robert et al. (2013) A critical analysis of the clinical use of incretin-based therapies: Are the GLP-1 therapies safe? Diabetes Care 36:2118-25
Saisho, Yoshifumi; Butler, Alexandra E; Manesso, Erica et al. (2013) *-cell mass and turnover in humans: effects of obesity and aging. Diabetes Care 36:111-7
Saisho, Yoshifumi; Butler, Alexandra E; Manesso, Erica et al. (2013) Response to Comment on: Saisho et al. *-cell mass and turnover in humans: effects of obesity and aging. Diabetes Care 2013;36:111-117. Diabetes Care 36:e112
Butler, Alexandra E; Campbell-Thompson, Martha; Gurlo, Tatyana et al. (2013) Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes 62:2595-604
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Elashoff, Michael; Matveyenko, Aleksey V; Gier, Belinda et al. (2011) Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 141:150-6
Daval, Marie; Gurlo, Tatyana; Costes, Safia et al. (2011) Cyclin-dependent kinase 5 promotes pancreatic ýý-cell survival via Fak-Akt signaling pathways. Diabetes 60:1186-97
Sdek, Patima; Zhao, Peng; Wang, Yaping et al. (2011) Rb and p130 control cell cycle gene silencing to maintain the postmitotic phenotype in cardiac myocytes. J Cell Biol 194:407-23

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