Pathogenesis of Diabetes Mellitus

Our research focuses on the development of abnormal glucose regulation in pathological states such as impaired glucose tolerance, type 1 (juvenile onset) and type 2 (adult onset) diabetes mellitus. Although it was thought that we are born with all of the insulin producing ?-cells we will ever have, new ?-cells are produced throughout life, and cells die through necrosis and apoptosis. With mathematical modeling applied to quantitative morphometry we can estimate the rates of cell death during development and aging. With this approach we are investigating the effect of insulin resistance, oral hypoglycemic agents and hyperglycemia on the stimulation of replication and induction of ?-cell death. In another project we are examining how cell death during development is linked to the initiation of type 1 diabetes. We hypothesize that impaired clearance of apoptotic ?-cells in the neonate triggers ?-cell directed autoimmunity.

Selected Publications:

Finegood, DT , Scaglia L, Bonner-Weir S. Dynamics of beta-cell mass in the growing rat pancreas: estimation with a simple mathematical model. Diabetes 44: 249-256, 1995.

Bell , RC, Ryan EA, DT Finegood . Consequences of high dietary fructose in the islet transplanted rat with subopitmal beta-cell mass. Am J Physiol 278: E292-E298, 1996.

Scaglia, L, CJ Cahill, DT Finegood , S Bonner-Weir. Apoptosis participates in the remodeling of the endocrine pancreas in the neonatal rat. Endocrinology 138:1736-1741, 1997.

Bell , RC and DT Finegood . Insulin levels increase during glycemic normalization following transplantation of syngeneic islets in diabetic rats. Can J Physiol Pharmacol 75: 952-958, 1997.

Finegood, DT . Application of the minimal model method. In: The Minimal Model Approach and Determinants of Glucose Tolerance. Bergman RN, Lovejoy JC, eds. Baton Rouge , LA : LA Univ Press; 1997, pp: 51-122.

Legro, R, DT Finegood , A Dunaif. A fasting glucose to insulin ratio is a useful measure of insulin resistance in women with polycystic ovary syndrome. J Clin Endocrinol Metab 83: 2694-2698, 1998.

Forbes, A, T Elliott, H Tildesley, DT Finegood and GS Meneilly. Alterations in non-insulin-mediated glucose uptake in the elderly patient with diabetes. J Clin Endocrinol Metab 47: 1915-1919, 1998.

Finegood, DT , GC Weir, S Bonner-Weir. Prior streptozotocin treatment does not inhibit pancreas regeneration following 90% pancreatectomy in rats. Am J Physiol 276: E822-827, 1999.

McArthur , MD , K Klapstein, D You, D Tzur, DT Finegood . Glucose effectiveness is the primary determinant of glucose tolerance in the normal rat. Am J Physiol 276: E739-746, 1999.

Topp, B, K Promislow, G deVries, RM Miura, DT Finegood . A Model of Beta-Cell Mass, Insulin, & Glucose Kinetics: Pathways to Diabetes. Journal of Theoretical Biology 206: 605-19, 2000.

McDonald, C, A Dunaif, DT Finegood . Minimal-Model Estimates of Insulin Sensitivity are Insensitive to Errors in Glucose Effectiveness. J Clin Endocrinol Metab 85:2504-2508, 2000.

Trudeau, JD, JP Dutz, E Arany , DJ Hill, WE Fieldus, DT Finegood . Perspectives in Diabetes. Neonatal ?-cell apoptosis: A trigger for autoimmune diabetes? Diabetes 49: 1-7, 2000.

Finegood, DT , MD McArthur, D Kojwang, MJ Thomas, BG Topp, T Leonard, RE Buckingham. *-Cell Mass Dynamics in Zucker Diabetic Fatty Rats: Rosiglitazone Prevents the Rise in Net Cell Death. Diabetes May 2001.