One of the chemical consequences of chronic hyperglycemia in diabetes is an increased body burden of glycated (nonenzymatically glycosylated) proteins. Glycation is recognized as the first step in a complex series of Maillard or browning reactions between glucose and protein which lead, in vitro, to the denaturation, crosslinking and insolubilization of protein. It is hypothesized that these same reactions may also occur in vivo, and that the alterations in protein structure may precipitate the development of pathology in tissues in diabetes and during normal aging. Indeed, the development of chronic complications in the eye, kidney and vasculature in diabetes is associated with increased crosslinking ahd insolubilization of lens, basement membrane and connective tissue proteins. Concomitant increases in glycation, browning and fluorescence of these long-lived extracellular proteins suggest that the Maillard reaction may be involved in these processes. The major objective of this research proposal is to continue studies on the glycation of protein and the role of the browning reaction of glycated proteins in the pathophysiology of diabetes and aging.
Specific aims i nclude: (1) structural characterization of Maillard products formed in model amino acid-glucose browning systems; (2) studies of factors which direct the specificity of glycation of protein in vitro and in vivo; (3) studies on the structure and mechanism of formation of fluorescent and crosslinking compounds generated during Maillard reactions of model proteins in vitro; and (4) development and application of methods for measurement of Maillard reaction products and their catabolites in vivo. We expect that a better understanding of the extent to which Maillard reactions occur in vivo under normal and pathological conditions will increase our understanding of their role in the complications of diabetes. This knowledge should provide a better basis for the design and evaluation of therapeutic approaches to the management of diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK019971-17
Application #
3483326
Study Section
Special Emphasis Panel (NSS)
Project Start
1977-08-01
Project End
1994-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
17
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of South Carolina at Columbia
Department
Type
Schools of Arts and Sciences
DUNS #
111310249
City
Columbia
State
SC
Country
United States
Zip Code
29208
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