Signaling mechanisms of insulin secretion. Cytokines and diabetes.
Insulin secretion, diabetes, cytokine, signal transduction.
Description of Research
My research lab is focused on the signal transduction mechanisms of insulin secretion from the islets of Langerhans within the context of understanding diabetes. Recently, we have identified a novel cytokine called PANDER (FAM3B) which is one of 4 cytokines of a new gene family FAM3. Veryl little is known about the cell biology of PANDER and the role of PANDER in islet biology. PANDER is expressed in islets of Langerhans and is present in secretory granules. PANDER causes apoptosis of beta-cells. PANDER mRNA is upregulated by interferon-gamma treatment in beta-cells. We have 2 working hypotheses that we are testing: is PANDER involved in cytokine-induced destruction of islets and the pathogenesis of type 1 diabetes, does PANDER have any role in beta-cell differentiation? The lab is using a combination of cell biological, biochemical and molecular biology approaches to understand the physiological role of PANDER and its role in diabetes.
Rotation Projects for 2006-2007
- Analysis of PANDER transgenic mouse
- Site-directed mutagenesis of PANDER
- siRNA approaches to downregulate PANDER
- Regulation of PANDER mRNA in beta-cells
- Secretory mechanisms of PANDER in beta-cells
Brant Burkhardt, PhD, Postdoctoral Fellow
Joshua Cook, Penn Undergraduate Student
Zhiyong Gao, MD, PhD, Lab Manager
Jason Carnegie, Graduate student (CAMB)
Scott Greene, Research Specialist
Claudia Robert, Graduate Student (CAMB)
Kelly McFadden, Penn Undergraduate Student
Jianmei Wu, Research Specialist
Jichun Yang, PhD, Postdoctoral Fellow
Robert Young, Research Specialist
Gao Z., Young RA., Li G., Najafi H., Buettger C., Sukumvanich SS., Wong RK., Wolf BA., Matschinsky FM.: Distinguishing features of leucine and alpha-ketoisocaproate sensing in pancreatic beta-cells. Endocrinology 144(5): 1949-57, May 2003.
Borge PD Jr., Wolf BA.: Insulin receptor substrate 1 regulation of sarco-endoplasmic reticulum calcium ATPase 3 in insulin-secreting beta-cells. Journal of Biological Chemistry 278(13): 11359-68, Mar 28 2003.
Desai NM., Goss JA., Deng S., Wolf BA., Markmann E., Palanjian M., Shock AP., Feliciano S., Brunicardi FC., Barker CF., Naji A., Markmann JF.: Elevated portal vein drug levels of sirolimus and tacrolimus in islet transplant recipients: local immunosuppression or islet toxicity? Transplantation 76(11): 1623-5, Dec 15 2003.
Bell E., Cao X., Moibi JA., Greene SR., Young R., Trucco M., Gao Z., Matschinsky FM., Deng S., Markman JF., Naji A., Wolf BA.: Rapamycin has a deleterious effect on MIN-6 cells and rat and human islets. Diabetes 52(11): 2731-9, Nov 2003.
Cao X., Gao Z., Robert CE., Greene S., Xu G., Xu W., Bell E., Campbell D., Zhu Y., Young R., Trucco M., Markmann JF., Naji A., Wolf BA.: Pancreatic-derived factor (FAM3B), a novel islet cytokine, induces apoptosis of insulin-secreting beta-cells. Diabetes 52(9): 2296-303, Sep 2003.
Deng S., Vatamaniuk M., Lian MM., Doliba N., Wang J., Bell E., Wolf B., Raper S., Matschinsky FM., Markmann JF.: Insulin gene transfer enhances the function of human islet grafts. Diabetologia 46(3): 386-93, Mar 2003.
Markmann JF., Deng S., Huang X., Desai NM., Velidedeoglu EH., Lui C., Frank A., Markmann E., Palanjian M., Brayman K., Wolf B., Bell E., Vitamaniuk M., Doliba N., Matschinsky F., Barker CF., Naji A.: Insulin independence following isolated islet transplantation and single islet infusions. Annals of Surgery 237(6): 741-9; discussion 749-50, Jun 2003.
Markmann JF., Deng S., Desai NM., Huang X., Velidedeoglu E., Frank A., Liu C., Brayman KL., Lian MM., Wolf B., Bell E., Vitamaniuk M., Doliba N., Matschinsky F., Markmann E., Barker CF., Naji A.: The use of non-heart-beating donors for isolated pancreatic islet transplantation. Transplantation 75(9): 1423-9, May 15 2003.
Gao Z., Young RA., Trucco MM., Greene SR., Hewlett EL., Matschinsky FM., Wolf BA.: Protein kinase A translocation and insulin secretion in pancreatic beta-cells: studies with adenylate cyclase toxin from Bordetella pertussis. Biochemical Journal 368(Pt 2): 397-404, Dec 1 2002.
Westerlund J., Wolf BA., Bergsten P.: Glucose-dependent promotion of insulin release from mouse pancreatic islets by the insulin-mimetic compound L-783,281. Diabetes 51 Suppl 1: S50-2, Feb 2002.
back to top
Last updated: 06/09/2011
The Trustees of the University of Pennsylvania