Keith Tornheim

keith-tornheimAssociate Professor

Boston University School of Medicine
Silvio Conte Building, Office: K108
72 E. Concord Street
Boston, MA 02118

Phone: 617-638-8296
Fax: 617-638-5339
Email
: tornheim@bu.edu

Education

BS, Chemistry, Antioch College, Yellow Springs, OH
PhD, Biochemistry, Brandeis University, Boston, MA

Research Interest

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.

Representative Publications

PubMed

  • Martinez-Costa, O.H., Sanchez, V., Lazaro, A., Hernandez, E.D., Tornheim, K., and Arago, J.J.  Distinct functional roles of the two terminal halves of eukaryotic phosphofructokinase.  Biochem. J. 2012, 445, 213-218.
  • Getty-Kaushik L, Viereck JC, Goodman JM, Guo Z, Lebrasseur NK, Richard AM, Flanagan JN, Yaney GC, Hamilton JA, Tornheim K. Mice Deficient in Phosphofructokinase-M Have Greatly Decreased Fat Stores.  Obesity 18, 434-440 (2010).
  • 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.
  • 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 beta-cells at substimulatory glucose. J. Biol. Chem. 278, 40710-40716.
  • 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.
  • 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., 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 beta -cells (HIT). Am. J. Physiol. 271, E702-E710.
  • 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 beta -cells. Biochemical J. 314, 91-94.
  • 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 beta -cells (INS-1). Diabetes 44, 1285-1289.
  • 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.