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Sweet_I_30[1]

Ian Sweet, Ph.D.

Metabolism, Endocrinology and Nutrition

Research Associate Professor
Director, Islet Core, UW DERC
Affiliate Investigator, Benaroya Research Institute


Focus

Understanding the dual role of mitochondrial energy production in mediating nutrient stimulated insulin secretion system and in maintaining viability of pancreatic beta cells. Methods have been developed to continuously assess oxygen consumption, cytochrome redox state, calcium and NAD(P)H levels in isolated islets concomitantly with insulin secretion. These techniques are being used to examine the bioenergetics of nutrient induced insulin secretion, the mechanisms of calcium mediated insulin secretion, real time kinetics of apoptosis and necrosis, the contribution of compromised islet function to the progression of type 2 diabetes and the acute and chronic effects of GLP-1 on islet function.


Research Interest

Understanding the dual role of mitochondrial energy production in mediating nutrient stimulated insulin secretion system and in maintaining viability of pancreatic beta cells.  Methods have been developed to continuously assess oxygen consumption, cytochrome redox state, calcium and NAD(P)H levels in isolated islets concomitantly with insulin secretion.  These techniques are being used to examine the bioenergetics of nutrient induced insulin secretion, the mechanisms of calcium mediated insulin secretion, real time kinetics of apoptosis and necrosis, the contribution of compromised islet function to the progression of type 2 diabetes and the acute and chronic effects of GLP-1 on islet function.  Specific applications have focused on assessing viability of human islets for transplantation; optimization of encapsulation techniques for transplanting immunoisolated islets; improving the response of islet function to hypoxia (a major issue in the preparation and transplantation of islets); and development of PET-based imaging methods to assess beta-cell mass in vivo.  Some of the methods we have developed are available as Core services through the DERC Islet Core (http://depts.washington.edu/diabetes/biomedcore/ifac.index.html).


Publications

Sweet IR, Najafi H, Li G, Berner DK, Matschinsky FM:  Effect of a glucokinase inhibitor on energy production and insulin release in pancreatic islets. Am J Physiol 271:E606-E625, 1996.

Sweet IR, Cook DL, Wiseman RW, Greenbaum CJ, Lernmark A, Matsumoto S, Teague JC, Krohn KA:  Dynamic perifusion to maintain and assess isolated pancreatic islets.  Diabetes Tech Ther 4:67-76, 2002.

Sweet IR, Khalil G, Wallen AR, Steedman M, Schenkman KA, Reems JA, Kahn SE, Callis JB:  Continuous measurement of oxygen consumption by pancreatic islets. Diabetes Tech Ther 4:661-672, 2002.

Sweet IR, Cook DL, DeJulio E, Wallen AR, Khalil G, Callis JB, Reems JA:  Regulation of ATP/ADP in pancreatic islets. Diabetes 53:401-409, 2004.

Sweet IR, Cook DL, Lernmark A, Greenbaum CJ, Stekhova S, Wallen A, Krohn KA:  Screening for beta cell imaging agents. Biochem Biophys Res Comm 314:976-983, 2004.

Sweet IR, Cook DL, Lernmark A, Greenbaum CJ, Krohn KA: Non-invasive imaging of beta cell mass:  A quantitative analysis. Diabetes Tech Ther 6:652-659, 2004.

Hampe CS, Wallen AR, Binder K, Schlosser M, Ziegler M, Sweet IR:  Quantitative evaluation of a monoclonal antibodies and its fragment as potential beta markers for pancreatic beta cell mass. Exp Clinical Endo Diabetes 113:381-387, 2005.

Sweet IR, Gilbert M, Sabek O, Fraga DW, Gaber AO, Reems JA: Glucose stimulation of cytochrome c reduction and oxygen consumption as assessment of human islet quality.  Transplantation 80:1003-1011, 2005.

Sweet IR, Gilbert M: Contribution of calcium influx in mediating glucose-stimulated oxygen consumption in pancreatic islets. Diabetes 55:3509-3519, 2006.

Sweet IR, Gilbert M, Scott S, Todorov I, Jensen R, Nair I, Al-Abdullah I, Rawson J, Mullen Y, Kandeel F, Ferreri K:  Glucose-stimulated increment in oxygen consumption rate as a standardized test of human islet quality.  Amer J Trans 8:183-192, 2008.