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Richard Kibbey, MD/PhD

Ensign Professor of Medicine (Endocrinology and Metabolism), and Professor of Molecular and Cellular Physiology
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Additional Titles

Faculty Director, Core in Chemical Metabolism

Associate Director, Yale Program for Translational Biomedicine

Associate Chief of Research, Endocrinology

About

Titles

Ensign Professor of Medicine (Endocrinology and Metabolism), and Professor of Molecular and Cellular Physiology

Faculty Director, Core in Chemical Metabolism; Associate Director, Yale Program for Translational Biomedicine; Associate Chief of Research, Endocrinology

Biography

Dr. Kibbey obtained his undergraduate degrees in music (B.A.) and an honors degree in biochemistry (B.S.) at Trinity University in San Antonio in 1991. He then obtained his combined M.D. and Ph.D. at the University of Texas Southwestern Medical School in 2000. His Ph.D. was in Cellular and Molecular Biophysics and involved determining the NMR structure of peptides from the LDL receptor under his mentors Drs. R.G.W. Anderson and L. Gierasch. Subsequently, he went to Yale University in where he was selected for the ABIM short-track in Categorical Internal Medicine. In 2002 he stayed on for his Endocrinology fellowship at Yale and is now board certified in Internal Medicine and Endocrinology. While in his fellowship he worked in the laboratory of Dr. Gerald Shulman on metabolism in the pathophysiology of Type-2 Diabetes Mellitus. Here he identified mitochondrial GTP as a metabolic signal in the mitochondria sensing flux in the pancreatic beta-cell as a crucial component of the signal to secrete insulin. His laboratory also has developed a novel platform using stable isotopes and mass spectrometry named Mass Isotopomer MultiOrdinate Spectral Analysis (MIMOSA) that measures the flow of metabolism inside and between tissues. He is now an Associate Professor in the Departments of Internal Medicine/Endocrinology and Cellular & Molecular Physiology. He continues to see patients at Yale Health and has an independent NIH-supported laboratory doing research on islet and whole body physiology in order to understand/prevent/treat Type-2 diabetes.

Appointments

Education & Training

Resident
Yale University School of Medicine (2002)
Intern
Yale University School of Medicine (2001)
MD/PhD
University of Texas Southwestern Medical School (2000)
BS
Trinity University (1991)
BA
Trinity University (1991)

Research

Overview

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, glucose production, nerve transmission, muscular contraction and normal and cancer cell growth. Mitochondria, therefore, require mechanisms to ‘sense’ their own metabolic environment in order to efficiently respond to supply and demand termed ‘metabolic equilibrioception.’ In order to better understand these and other important mitochondrial metabolic fluxes, methods to discriminate between oxidative, exchange, anaplerotic, and cataplerotic fluxes were developed. Consequently, the LC/MS/MS method Mass Isotopomeric Multi-Ordinate Spectroscopic Analysis (MIMOSA) follows the step-wise flow of mass isotopomers along these intersecting metabolic pathways. It captures both steady state and dynamic metabolic fluxes by resolving positional isotopomers of the TCA cycle. As a consequence, MIMOSA not only can determine the rates of individual intracellular fluxes but, when more than one pathway compete for a reaction, the relative flow of each contribution.

From the study of a rare condition of congenital hypoglycemia, the Kibbey lab identified mitochondrial GTP (mtGTP) as an important equilibrioceptive indicator involved in glucose homeostasis and ascribed the first physiological activity of the mitochondria GTP cycle as a “metabolic tachometer.” In tissues such as pancreatic b-cells and hepatocytes, the mtGTP is hydrolyzed by the mitochondrial isoform of phosphoenolpyruvate carboxykinase (PEPCK-M) to generate PEP that is essential for insulin secretion, while in hepatocytes it catalyzes this crucial step of gluconeogenesis. Finally, it also regulates glucagon secretion from a-cells.

His laboratory has developed a unique experience with mitochondrial, cellular, tissues-specific and whole body metabolism needed to advance mtGTP understanding. It is strongly vested in both understanding intracellular and inter-tissue metabolic flux associated with metabolic human disease. Differences in equilibrioception and responses to pharmacologic therapy are used to identify defects in metabolism as novel therapeutic targets for humans. While Dr. Kibbey’s graduate studies were NMR protein structure, his expertise now lies in 13C mass spectrometry, insulin resistance and secretion, bioenergetics, and applications to cellular, cancer and animal preclinical models.

Medical Subject Headings (MeSH)

Diabetes Mellitus, Type 2; Endocrinology; Glucose; Insulin; Mass Spectrometry; Metabolism; Mitochondria; Physiology

Research at a Glance

Yale Co-Authors

Frequent collaborators of Richard Kibbey's published research.

Publications

2024

2023

Academic Achievements & Community Involvement

  • activity

    "Glucose Regulation of B-Cell KATP Channels: Is a New Model Needed?" -https://thesugarscience.org/ask-the-expert/

  • activity

    American Diabetes Association

  • activity

    How beta-cells (really) sense glucose

  • activity

    Tracer Studies Using MIMOSA – A New Window on Quantitative Fluxomics

  • activity

    How beta-cells (really) sense glucose

Get In Touch

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