Burton Wice, PhD
Research Associate Professor of Medicine
University of Missouri-Columbia, Columbia, MO (1971-1974)
University of Missouri-St. Louis, St. Louis, MO, B.A. in Biology (1975)
Washington University, St. Louis, MO, Ph.D. (1992)
Dr. Wice received his Doctoral and Post-Doctoral training at Washington University in Saint Louis in the laboratory of Dr. Jeffrey Gordon where he studied intestinal epithelial cell biology. He joined the faculty in the Department of Internal Medicine, Division of Endocrinology, Metabolism, and Lipid Research in 1999.
To understand the molecular mechanisms that regulate the incretin response: The entero-insulin axis is a physiological system which comprises peptides secreted from enteroendocrine cells in the gastrointestinal tract that play an important role in regulating insulin secretion from the pancreatic islet beta cell. To date, attention has focused on two intestinal peptides- GLP-1 and GIP. GLP-1 is produced by L cells located in the distal intestine whereas GIP is produced predominantly by K cells in the proximal small intestine. Both peptides are released into the blood immediately after ingestion of a meal and potentiate glucose-stimulated insulin release. The increase in insulin secretion resulting from the actions of these “incretin peptides” has been termed the incretin effect. Critically, this effect occurs only in the presence of elevated blood glucose which prevents continued insulin release and subsequent hypoglycemia once blood glucose levels return to normal. Because they effectively and safely reduce blood glucose levels, incretin therapies have been developed to treat type 2 diabetes mellitus (T2DM). Exenatide is a long-acting GLP-1 analogue whereas sitagliptin increases endogenous GLP-1 levels by inhibiting GLP-1 breakdown. Both agents are in widespread clinical use to treat T2DM. In contrast to GLP-1, persons with T2DM are resistant to the actions of exogenous GIP. Thus, molecules that increase GIP signaling have generally not been pursued as incretin therapies. However, if the response to GIP could be restored, GIP-based therapies could represent novel and important new approaches to the treatment of T2DM. Current studies in my laboratory are focusing on elucidating the mechanisms that regulate GIP-mediated insulin release and reduction in hyperglycemia in healthy humans and well as in those with T2DM. We have identified a peptide called xenin-25 that potentiates GIP action in mouse models of hyperglycemia. We are currently conducting studies in rodents to determine how xenin-25 increases insulin release and in humans to determine whether xenin-25 also potentiates GIP action in healthy individuals and in those with T2DM. Additional studies are underway to identify novel intestinal peptides that may also regulate insulin release from pancreatic islet beta cells.