Richard G. Kibbey, M.D., Ph.D.

Assistant Professor of Medicine and Cellular & Molecular Physiology
Section of Endocrinology & Metabolism

Dr. Richard Kibbey is an Assistant Professor of Medicine and Physiology at Yale University School of Medicine. His special interests are in Type-2 diabetes and metabolic diseases. Dr. Kibbey is Board Certified in both Internal Medicine and Endocrinology and Metabolism. He has been a member of the Yale Medical School faculty since 2007.

Clinical Interests

Dr. Kibbey attends on general Internal Medicine and the Endocrine Consult team at Yale New Haven Hospital and has a general endocrinology clinic at the Yale University Health Services. He is a member of the Yale Medical Group as well as the Connecticut State Medical Society and the American Diabetes Association.

Research Interests

Dr. Kibbey’s lab is primarily interested in the elucidation at a cellular and molecular level how the mitochondria in β-cells and liver act to sense and regulate energy homeostasis in particular as it pertains to Type 2 Diabetes Mellitus (T2DM). In particular we are focused on how the mitochondrial GTP metabolic circuit regulates insulin secretion and gluconeogenesis.

The physiologic control of glucose homeostasis is an integrated multi-component process where hormonal, sensory, and nutritional inputs and outputs cooperate to ensure proper energy balance. T2DM results from dysfunctional integration of this regulatory network and frequently associated with increased insulin resistance or inadequate insulin secretion. Mitochondria, as the primary sites of consumption and production of metabolites and energy, are central to both of these. Mitochondria, therefore, require mechanisms to ‘sense’ their own metabolic environment in order to efficiently respond to supply and demand.

The Kibbey lab has identified one such signal, mitochondrial GTP (mtGTP), as an important ‘fuel-sensor’ involved in glucose homeostasis. Every turn of the TCA cycle generates stoichiometric amounts of mtGTP by the enzyme Succinyl-CoA Synthetase, and as such mtGTP synthesis acts as a ‘molecular tachometer’ of mitochondrial metabolic flux. In tissues such as pancreatic β-cells and hepatocytes, the mtGTP is hydrolyzed by the mitochondrial isoform of phosphoenolpyruvate carboxykinase (PEPCK-M) to generate phosphoenolpyruvate (PEP). In β-cells, this creates a trans-mitochondrial PEP cycle essential for insulin secretion, while in hepatocytes it catalyzes the rate-limiting step of gluconeogenesis. We are trying to identify how this mtGTP metabolic circuit in β-cells and the liver regulates glucose homeostasis.

Representative Publications

• Stark, R., Pasquel, F., Turcu, A., Pongratz, R.L., Roden, M., Cline, G.W., Shulman, G.I., and Kibbey, R.G. (2009). Phosphoenolpyruvate cycling via mitochondrial PEPCK links anaplerosis and mitochondrial GTP with insulin secretion. J Biol Chem.(Epub)
• Kibbey, R.G., Pongratz, R.L., Romanelli, A.J., Wollheim, C.B., Cline, G.W., and Shulman, G.I. (2007). Mitochondrial GTP regulates glucose-stimulated insulin secretion. Cell Metab 5, 253-264.
• Pongratz, R.L., Kibbey, R.G., Shulman, G.I., and Cline, G.W. (2007). Cytosolic and mitochondrial malic enzyme isoforms differentially control insulin secretion. J Biol Chem 282, 200-207.
• Cline, G.W., Lepine, R.L., Papas, K.K., Kibbey, R.G., and Shulman, G.I. (2004). 13C NMR isotopomer analysis of anaplerotic pathways in INS-1 cells. J Biol Chem 279, 44370-44375.

Education:	M.D., University of Texas Southwestern Medical School, 2000 Ph.D., University of Texas Southwestern Medical School in Cellular and Molecular Biophysics, 2000
Training:	Internship and Residency: Yale University School of Medicine, 2000-2002 Endocrinology Fellowship: Yale University School of Medicine, 2002-2005

Contact

Campus Address
Department of Internal Medicine
Section of Endocrinology
Yale University
School of Medicine
PO Box 208020
New Haven, CT
06520-8020

E-mail
richard.kibbey@yale.edu

Office Phone
203.737.4055

Fax
203.785.3823