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Division of Endocrinology, Diabetes & Metabolism

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Research


EndoLab_LaRock250x180The Division includes several nationally recognized research programs in pancreatic ß-cell biology, muscle and adipose physiology, insulin resistance, nutrition, obesity, lipid biochemistry, and type 2 diabetes.

Our principal investigators spearhead basic and clinical research programs with extensive collaborations within and outside the institution. Particularly strong elements are the complementary backgrounds and multidimensional research perspectives of the faculty--clinical and basic science experience coupled with state-of-the-art biochemical, molecular, and cellular biology expertise extending to the whole animal and human physiology.

Historically, the Division has an impressive record of landmark clinical investigations that continues today in translational research on energy balance and metabolism in humans and on the effects of dietary fat content on liver and muscle glucose utilization, and muscle lipid metabolism, on diabetes, obesity, and cardiovascular risk (Dr. C.L. Kien, PI). These studies include metabolic assessments, measurements of VO2 peak and daily physical activity (accelerometry), muscle and fat biopsy, and an array of molecular, biochemical and metabolomic endpoints with state of the art instrumentation and complex statistical analysis of large data sets (e.g. principal components analysis).

Other translational research projects in the Division include studies on the effects of short chain fatty acids on gut mucosal physiology, pancreatic ß-cell growth, and diabetes risk (Dr. C.L. Kien, PI). The studies are based on the premise that the ingestion of starches and sugars, not fully digested in the human intestine, may provide medical benefit through the microbial production of butyric acid; published work as well as recent preliminary data indicate that butyrate may alter intestinal growth, and enhance β-cell function and peripheral insulin sensitivity.

Key to the basic research initiatives of the Division has been the establishment of a pancreatic Islet Biology Consortium consisting of laboratories with long-standing interests in the development, regeneration, function, and physiological regulation of the insulin-producing ß-cell. Members of the Consortium include Drs. J. Leahy, J. Gupta, T. Jetton, and C.L. Kien. Current projects include:

● ß-cell PPAR-gamma signaling in obesity
● effects of PPAR-gamma agonists and DPP-4 inhibitors on ß-cell mass and function
● the role of PPAR-gamma in ß-cell compensation following partial pancreatectomy
● PPAR-gamma signaling in adaptive islet growth and function
● neural and dietary regulation of ß-cell mass and function.


Research Facilities


OutsideCRF250x180The Division's basic research group is located at the Colchester Research Facility (CRF), a five-minute drive from the main UVM campus.

The main laboratory areas are on the first floor and comprise ~2,400 sq. ft. total of general lab space. Adjoining this laboratory area are:

● state-of-the-art tissue culture facility with separate, dedicated rodent and human tissue rooms and hoods
● advanced microscope/imaging facility
● nearby cold room, fully equipped darkroom, and an autoclave room
● specialized rooms dedicated to radioisotope usage, pancreatic islet isolation, UV light box and gel documentation workstation, a microplate reader, low and medium speed centrifuges, and ultra-low freezers

The second floor of CRF houses a modern animal care facility for the general housing and breeding of rodents, and our group shares a state-of-the-art ~400 sq. ft. animal procedure room with four surgery bays equipped with Snorkel vents, an anesthesia machine, Olympus microsurgery scopes with fiber-optic lighting, specialized procedure benches, and recovery stations. Adjoining this room is a 144 sq. ft. specialized procedure room, institutionally approved for long-term experiments such as chronic rodent infusion, metabolic, feeding, and drug studies.

Major Equipment


● ABI 7300 quantitative PCR workstation
● Leica embedding workstation for routine light microscopic preparation
● Hitachi visible light and UV spectrophotometer workstation
● Olympus stereoscopes with darkfield/transmitted, and reflected light capabilities for pancreatic islet isolation and purification
● imaging workstation with a Zeiss Universal and research-grade Zeiss inverted photomicroscopes for widefield epifluorescence and phase contrast analysis equipped with a Spot RT digital color CCD camera
● Nikon-TiE multi-channel fluorescence imaging/morphometry workstation for live cell and fixed tissue quantitative analyses, equipped with a Retiga-SRV ultra-sensitive CCD, Ludl motorized stage controllers driven by Nikon Elements software, and an array of Plan Apo objectives with appropriate filter sets for UV to far-red excitation/emission
● G5 Macintosh imaging workstations running the latest image analysis software
● metabolic cart (indirect calorimeter) configured for both continuous flow-through (canopy) studies and exercise studies (mouthpiece) Vmax 29, (Sensor Medics Corp), an Agilent 6890N Network Gas Chromatography System with autoinjector module, autosampler tray, and ChemStation software, and a Savant Speed Vac refrigerated concentrator.

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