Abstract

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

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK077967-08
Application #
9117479
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Sato, Sheryl M
Project Start
2007-04-01
Project End
2017-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
8
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

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

  Publications

Butler, Alexandra E; Sacks, Wendy; Rizza, Robert A et al. (2017) Down Syndrome-Associated Diabetes Is Not Due To a Congenital Deficiency in ? Cells. J Endocr Soc 1:39-45
Moin, Abu Saleh Md; Butler, Peter C; Butler, Alexandra E (2017) Increased Proliferation of the Pancreatic Duct Gland Compartment in Type 1 Diabetes. J Clin Endocrinol Metab 102:200-209
Md Moin, Abu Saleh; Cory, Megan; Ong, Allison et al. (2017) Pancreatic Nonhormone Expressing Endocrine Cells in Children With Type 1 Diabetes. J Endocr Soc 1:385-395
Schludi, Belinda; Moin, Abu Saleh Md; Montemurro, Chiara et al. (2017) Islet inflammation and ductal proliferation may be linked to increased pancreatitis risk in type 2 diabetes. JCI Insight 2:
Montemurro, Chiara; Vadrevu, Suryakiran; Gurlo, Tatyana et al. (2017) Cell cycle-related metabolism and mitochondrial dynamics in a replication-competent pancreatic beta-cell line. Cell Cycle 16:2086-2099
Gurlo, Tatyana; Butler, Peter C; Butler, Alexandra E (2016) Evaluation of immunohistochemical staining for glucagon in human pancreatic tissue. J Histotechnol 39:8-16
Md Moin, Abu Saleh; Dhawan, Sangeeta; Cory, Megan et al. (2016) Increased Frequency of Hormone Negative and Polyhormonal Endocrine Cells in Lean Individuals With Type 2 Diabetes. J Clin Endocrinol Metab 101:3628-3636
Md Moin, Abu Saleh; Dhawan, Sangeeta; Shieh, Christine et al. (2016) Increased Hormone-Negative Endocrine Cells in the Pancreas in Type 1 Diabetes. J Clin Endocrinol Metab 101:3487-96
Butler, Peter C (2016) Glucagon-like Peptide 1 Drugs as Second-line Therapy for Type 2 Diabetes. JAMA Intern Med 176:1-3
Butler, Alexandra E; Dhawan, Sangeeta; Hoang, Jonathan et al. (2016) ?-Cell Deficit in Obese Type 2 Diabetes, a Minor Role of ?-Cell Dedifferentiation and Degranulation. J Clin Endocrinol Metab 101:523-32

Showing the most recent 10 out of 31 publications