Richard Glenn Kibbey, MD/PhD

Associate Professor of Medicine (Endocrinology) and of Cellular And Molecular Physiology

Research Interests

Diabetes Mellitus, Type 2; Endocrinology; Glucose; Insulin; Mitochondria; Physiology

Research Organizations

Internal Medicine: Diabetes Research Center | Endocrinology: Fellowship Training | Liver Center

Cellular & Molecular Physiology

Cancer Center: Signal Transduction

Office of Cooperative Research

Research Summary

The control of glucose homeostasis is a multi-component process where hormonal, sensory, and nutritional inputs and outputs cooperate to ensure proper energy balance. Diabetes mellitus results from dysfunctional integration of this regulatory network and is frequently associated with increased insulin resistance or inadequate insulin secretion. Mitochondria are central to both of these. Mitochondria, therefore, require mechanisms to 'sense' their own metabolic environment in order to respond to supply and demand. My 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, and as such mtGTP synthesis acts as a 'molecular tachometer' of mitochondrial metabolic flux. In tissues such as pancreatic cells and hepatocytes, the mtGTP is hydrolyzed by mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) to generate PEP. In ßcells, this creates a trans-mitochondrial PEP cycle essential for insulin secretion, while in hepatocytes it catalyzes the rate-limiting step of luconeogenesis. We are trying to identify how this mtGTP metabolic circuit in ßcells and the liver regulates glucose homeostasis.

Specialized Terms: Mechanisms of insulin secretion by beta-cells; Pathogenesis of beta-cell exhaustion in Type 2 Diabetes Mellitus; Mitochondria

Extensive Research Description

Dr. Kibbey is interested in the mechanisms of insulin secretion by beta-cells and the pathogenesis of beta-cell exhaustion in Type 2 Diabetes Mellitus. Recent studies have demonstrated that the production of mitochondrial GTP is an important indicator of TCA cycle flux and may represent a key regulator of insulin secretion. His lab is also developing animal models of chronic hyperglycemia in order to study the effects of glucose toxicity on insulin secretion by pancreatic islet cells.

Selected Publications

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Contact Info

Richard Glenn Kibbey, MD/PhD
Patient Care Locations
Inpatient Consultations requested by a physicianYale-New Haven Hospital
20 York Street

New Haven, CT 06510
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Specialty ClinicsYale Health Center
55 Lock Street

New Haven, CT 06511
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Lab Location
The Anlyan Center
300 Cedar Street, Ste S 110

New Haven, CT 06519
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Office Location
The Anlyan Center
300 Cedar Street, Ste S 113

New Haven, CT 06519
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Mailing Address
PO Box 208020
300 Cedar Street

New Haven, CT 06520-8020