The islets of Langerhans which are distributed throughout the pancreas comprise 1-2% of the mass of the pancreas and contain the endocrine cells that secrete insulin (beta-cells) and other hormones. The overall goal of the studies outlined in this application is to provide a better understanding of normal physiological changes in islet number, size, shape, distribution and cellular composition associated with aging with the expectation that the results will provide a foundation to further study the processes in response to perturbations such as chronic metabolic diseases. Here we propose to use novel large-scale imaging techniques to describe and quantify changes in human pancreatic islets as a function of age. This application is a collaboration between investigators at the University of Chicago and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and has one specific aim:
Specific Aim : Quantitative analysis of changes in human pancreatic islets as a function of age The proposed study will provide a detailed understanding of the effect of aging on human pancreatic islets and the genes and pathways involved. The results form the foundation for future studies of human pancreatic islets under physiological and pathophysiological conditions. The primary data and analyses will be made available to the diabetes community through an online library for follow-up analyses.

Public Health Relevance

The overall goal of this project is to characterize the number, size, shape, distribution and cellular composition of human pancreatic islets as a function of age. The results will provide a better understanding of the normal changes in islets that occur as we age and a foundation for similar studies under other physiological and pathophysiological conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
5R03AG042151-02
Application #
8554752
Study Section
Cellular Aspects of Diabetes and Obesity Study Section (CADO)
Program Officer
Murthy, Mahadev
Project Start
2012-09-30
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$74,655
Indirect Cost
$27,405
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Fowler, Jonas L; Lee, Steve Seung-Young; Wesner, Zachary C et al. (2018) Three-Dimensional Analysis of the Human Pancreas. Endocrinology 159:1393-1400
Greeley, Siri Atma W; Zielinski, Mark C; Poudel, Ananta et al. (2017) Preservation of Reduced Numbers of Insulin-Positive Cells in Sulfonylurea-Unresponsive KCNJ11-Related Diabetes. J Clin Endocrinol Metab 102:1-5
Olehnik, Scott K; Fowler, Jonas L; Avramovich, Gil et al. (2017) Quantitative analysis of intra- and inter-individual variability of human beta-cell mass. Sci Rep 7:16398
Poudel, Ananta; Fowler, Jonas L; Zielinski, Mark C et al. (2016) Stereological analyses of the whole human pancreas. Sci Rep 6:34049
Hoang, Danh-Tai; Hara, Manami; Jo, Junghyo (2016) Design Principles of Pancreatic Islets: Glucose-Dependent Coordination of Hormone Pulses. PLoS One 11:e0152446
Poudel, Ananta; Savari, Omid; Striegel, Deborah A et al. (2015) Beta-cell destruction and preservation in childhood and adult onset type 1 diabetes. Endocrine 49:693-702
McKenna, Brian; Guo, Min; Reynolds, Albert et al. (2015) Dynamic recruitment of functionally distinct Swi/Snf chromatin remodeling complexes modulates Pdx1 activity in islet ? cells. Cell Rep 10:2032-42
Grapov, Dmitry; Fahrmann, Johannes; Hwang, Jessica et al. (2015) Diabetes Associated Metabolomic Perturbations in NOD Mice. Metabolomics 11:425-437
Hoang, Danh-Tai; Matsunari, Hitomi; Nagaya, Masaki et al. (2014) A conserved rule for pancreatic islet organization. PLoS One 9:e110384
Wang, Xiaojun; Misawa, Ryosuke; Zielinski, Mark C et al. (2013) Regional differences in islet distribution in the human pancreas--preferential beta-cell loss in the head region in patients with type 2 diabetes. PLoS One 8:e67454

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