Keith Tornheim
Associate Professor of Biochemistry
Department of Biochemistry
Boston University School of Medicine
Evans Biomedical Research Center, X816
650 Albany Street
Boston, MA 02118
Phone: 617-638-8296
Fax: 617-638-7035
Email: tornheim@bu.edu
Education
B.S., Antioch College, Yellow Springs, OH
Ph.D., Brandeis University, Boston, MA
Research Interest
Metabolic oscillations and insulin secretion.
I previously studied spontaneous oscillatory behavior of glycolysis in muscle extracts. These oscillations involve the regulatory properties of the key control enzyme, phosphofructokinase, which was therefore the object of related kinetic studies. We are now testing the hypothesis that such oscillatory behavior of glycolysis and the ATP/ADP ratio underlies glucose-stimulated oscillations in intracellular free Ca2+ and insulin secretion in pancreatic islets. Such oscillations can increase the potency of insulin, and loss or derangement of these oscillations may contribute to the development of type 2 diabetes.
Fuel metabolism and AMP-activated protein kinase in vascular tissue, muscle and other tissues. This research project, in collaboration with other members of the Diabetes and Metabolism Unit, in part concerns the metabolic changes that may be responsible for the frequently occurring vascular complications of diabetes.
Representative Publications
Andres, V., Schultz, V., and Tornheim, K. (1990) Oscillatory synthesis of glucose 1,6-bisphosphate and frequency modulation of glycolytic oscillations in skeletal muscle extracts. J. Biol. Chem. 265, 21441-21447.
Yaney, G.C., Schultz, V., Cunningham, B.A., Dunaway, G.A., Corkey, B.E., and Tornheim, K. (1995) Phosphofructokinase isozymes in pancreatic islets and clonal ? -cells (INS-1). Diabetes 44, 1285-1289.
Nilsson, T., Schultz, V., Berggren, P.-O., Corkey, B.E. and Tornheim, K. (1996) Temporal patterns of changes in ATP/ADP ratio, glucose 6-phosphate and cytoplasmic free Ca2+ in glucose-stimulated pancreatic ? -cells. Biochemical J. 314, 91-94.
Cunningham, B.A., Deeney, J.T., Bliss, C.R., Corkey, B.E., and Tornheim, K. (1996) Glucose-induced oscillatory insulin secretion in perifused rat pancreatic islets and clonal ? -cells (HIT). Am. J. Physiol. 271, E702-E710.
Dagher, Z., Ruderman, N., Tornheim, K., and Ido, Y. “Fatty acid oxidation, glucose metabolism and ATP generation in human umbilical vein endothelial cells (HUVEC): Effects of AICAR.” Circ. Res. 88, 1276-1282 (2001).
Cunningham, B. A., Richard, A.-M. T, Dillon, J. S., Daley, J. T., Civelek, V. N., Deeney, J. T., Yaney, G. C., Corkey, B. E., and Tornheim, K. (2003) Glucagon-like peptide 1 and fatty acids amplify pulsatile insulin secretion from perifused rat islets. Biochemical J. 369, 173-178.
Juntti-Berggren, L., Webb, D.-L., Arkhammar, P. O. G., Schultz, V., Elke K. H. Schweda, E. K. H., Tornheim, K., and Berggren, P.-O. (2003) Dihydroxyacetone-induced oscillations in cytoplasmic free Ca2+ and the ATP/ADP ratio in pancreatic ?-cells at substimulatory glucose. J. Biol. Chem. 278, 40710-40716.
Richard, A.M., Webb, D. L., Goodman, J. M., Schultz, V., Flanagan, J. N., Getty-Kaushik, L., Deeney, J. T., Yaney, G. C., Dunaway, G. A., Berggren, P. O., Tornheim, K. (2007) Tissue-dependent loss of phosphofructokinase-M in mice with interrupted activity of the distal promoter: impairment in insulin secretion. Am. J. Physiol. 293, E794-E801.
