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| Thanks to the following for materials & support |
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Diabetes
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| The integrated technologies of the BRC have opened new windows into diabetes 1 & 2, as well as the underlying pathophysiology, by taking advantage of our core R&D emphasis on developing tools for tracking cellular metabolism. |
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Adenoviral transduction of malic enzyme (green) in a cluster of pancreatic β-cells. Nuclei (blue) and insulin granules (red) are shown. Malic enzyme converts malate to pyruvate which is an integral part of the metabolic process behind glucose stimulated insulin release. Studies by Heart et al (2009) suggest new alternatives for the regulation of pulsatile release of insulin at the level of the pancreatic β-cell. These observations have clear implications for our understanding and possible treatment of diabetes. Scale bar is 10µm.
Heart, E., Cline, G.W., Collis, L.P., Pongratz, R.L. Gray J. and Smith, P.J. S. 2009. Role for malic enzyme, pyruvate carboxylation and mitochondrial malate import in the glucose-stimulated insulin secretion. Am J Physiol Endocrinol Metab. (In press)
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| • Beta cell oscillatory response is not a result of a single component action >> |
| • Neuronal glucose detection & hypoglycemia- associated autonomic failure >> |
| • Metabolic consequences of neuronal excital toxicity >> |
| • Effects of hyperglycemia on living mouse embryos >> |
| • Myocellular energy metabolism: studies using self-referencing microelectrodes >> |
| • The mechanism of action of a newly developed blood glucose-lowering hormone >> |
• Functional heterogeneity of mitochondria in an individual
pancreatic beta cell >> |
| • Incretin action of fatty acids in glucose-stimulated insulin secretion >> |
• Imaging the distribution & movement of bodipy-FA in beta cells
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| • Modulation of pancreatic islet activity >> |
| • Insulin secretion from pancreatic beta cells >> |
| • Beta cell oxygen consumption >> |
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| Li R., Chase, M., Jung, S.K., Smith, P.J.S., and Loeken, M.R. 2005. Hypoxic stress in diabetic pregnancy contributes to defective embryo gene expression and defective development by inducing oxidative stress. American Journal of Physiology-Endocrinology and Metabolism, 289: E591-E599. |
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MacLellan, J. D., Gowing, A., Gerrits, M., Smith, P.J.S., Sivitz, W., Wheeler, M. B., and Harper, M. E. 2005. Physiological increases in uncoupling protein 3 augment fatty acid oxidation and decrease reactive oxygen species production without unoupling muscle cells. Diabetes, 54:2343-2350.
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Katzman, S.M., Messerli, M.A., Barry, D.T, Grossman, A., Harel,T., Wikstrom, J.D., Corkey, B.E., Smith, P.J.S., Shirihai,O.S. 2004. Mitochondrial metabolism reveals a functional architecture in intact islets of Langerhans from normal and diabetic Psammomys obesus. American Journal of Physiology-Endocrinology and Metabolism, 287: E1090-E1099.
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Wikstrom, J.D., Katzman, S.M., and Shirihai, O.S. 2004. Functional heterogeneity of mitochondria in an individual beta cell. Diabetologia, 47: A26.
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Wikstrom, J.D., Katzman, S.M., and Shirihai, O.S. 2002. Functional diversity of mitochondria within single pancreatic islet cells demonstrates patterns unique to healthy and diabetic islets. Biological Bulletin, 208: 268.
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| Jung, S.-K., Trimarchi, J.R., Sanger, R.H. and Smith, P.J.S. 2001. Development and application of a self-referencing glucose microsensor for the measurement of glucose consumption by pancreatic beta cells. Analytical Chemistry, 73(15): 3759-3767. |
| Jung, S.-K., Hammar, K. and Smith, P.J.S. 2000. Development of self-referencing oxygen microsensor and its application to HIT cells. Biological Bulletin, 199(2): 197-198. |
| Porterfield, D.M., Corkey, R.F., Sanger, R.H., Tornheim, K., Smith, P.J.S. and Corkey, B.E. 2000. Oxygen consumption oscillates in single clonal pancreatic beta -cells (HIT). Diabetes, 49: 1511-1516. |
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Equipment
