Dr. Kibbey is a clinically-active physician scientist dedicated to the treatment of diabetes and other metabolic diseases. Mitochondria, as the primary sites of consumption and production of metabolites and energy, are central to regulation of insulin secretion and glucose production. Mitochondria, therefore, require mechanisms to ‘sense’ their own metabolic environment in order to efficiently respond to supply and demand termed ‘metabolic equilibrioception.’ He has developed a special expertise in measuring the flow of intermediary metabolism and built the LC/MS/MS method Mass Isotopomeric Multi-Ordinate Spectroscopic Analysis (MIMOSA) as a technique to resolve the complex and interwoven isotopomer patterns generated by mitochondrial metabolism. He directs the IOMIC metabolism core, co-directs a cell biology core, co-founded a spin-off company, and directs a graduate course in intermediary metabolism and bioenergetics.
From the study of a rare condition of congenital hypoglycemia, the Kibbey lab identified mitochondrial GTP (mtGTP) as an important component of the glucose-sensing mechanism for pancreatic beta-cells. In this pathway glucose concentration is conveyed to the rest of the cell through a trans-mitochondrial metabolic cycle. In this so called “PEP cycle”, mitochondrial metabolic inputs are integrated through the metabolism of mtGTP and anaplerosis via the mitochondrial isoform of PEPCK to make phosphoenolpyruvate (PEP). PEP has the highest energy phosphate bond in the cell, which through the action of pyruvate kinase lowers cytosolic ADP to trigger depolarization. This has led to the identification of small molecules that can activate the PEP cycle that amplifyinsulin secretions in diabetic rodent models and human islets. He is working to translate it into a new class of diabetes and cancer therapeutics. While Dr. Kibbey’s trained in NMR protein structure, his expertise now lies in 13C mass spectrometry, islet biology, insulin resistance and secretion, bioenergetics, and applications to cellular, cancer and animal preclinical models.
