eBriefing

Restoring Pancreatic Function in Diabetes

Restoring Pancreatic Function in Diabetes

Overview

Much of the development of type 2 diabetes can be traced to a cluster of cells in the pancreas, known as the Islets of Langerhans—or simply as beta cells. Beta-cell dysfunction or loss of cell mass appears to result in the hallmark symptom of diabetes, impaired or reduced glucose-stimulated insulin secretion.

Pancreatic beta cells have long been the focus of research to unravel this complex disease. Yet the precise etiology of insulin resistance is still not yet clearly understood. On February 24, 2004, leading experts in the field of endocrinology, biotechnology, pharmacology, and imaging technology gathered at the Academy in New York to share their findings. The symposium also explored approaches to restoring pancreatic function in type 2 diabetes.

Web Sites

Clinical Trials for Diabetes
From the National Institutes of Health, a project "linking patients to medical research," as part of the Library of Medicine. Its comprehensive listing of clinical trials notes up front which are now recruiting.

Joslin Diabetes Center
The research center's public face, with news, online classes, and nutrition advice.

Medline Plus Diabetes
News and public-health information, from diagnosis to "coping," sponsored by the National Institutes of Health.

National Diabetes Information Clearinghouse (NDIC)
A service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), itself part of the National Institutes of Health. The NDIC was established in 1978 to increase knowledge and understanding about diabetes among patients, health care professionals, and the general public.


Books

Porte, Daniel, Robert S. Sherwin, Alain Baron et al. 2002. Ellenberg and Rifkin's Diabetes Mellitus. McGraw-Hill, New York.
Amazon | Barnes & Noble

Wass, J. A. H., Stephen Shalet & Edwin A. M. Gale, Eds. 2002. Oxford Textbook of Endocrinology and Diabetes. Oxford University Press, New York.
Amazon | Barnes & Noble


Journal Articles

Ahren, B., J. J. Holst & A. Mari. 2003. Characterization of GLP-1 effects on beta cell function after meal ingestion in humans. Diabetes Care 26: 2860-2864.

Bertera, S., X. Geng, Z. Tawadrous et al. 2003. Body window-enabled in vivo multicolor imaging of transplanted mouse islets expressing an insulin-timer fusion protein. BioTechniques 35: 718-722.

Chen, G., H. E. Hohmeier & C. B. Newgard. 2001. Expression of the transcription factor STAT-1 in insulinoma cells protects against cytotoxic effects of multiple cytokines. J. Biol. Chem. 276: 766-772. Full Text

Deacon, C. F., T. E. Hughes & J. J. Holst. 1998. Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of glucagon-like peptide 1 in the anesthetized pig. Diabetes 47: 764-769. Full Text [PDF 199 KB]

Federici, M., M. Hribal, L. Perego et al. 2001. High glucose causes apoptosis in cultured human pancreatic islets of langerhans: a potential role for regulation of specific Bcl family genes toward an apoptotic cell death program. Diabetes 50: 1290-1301. Full Text

Grimm, J., A. Potthast, A. Wunder & A. Moore. 2003. Magnetic resonance imaging of the pancreas and pancreatic tumors in a mouse orthotopic model of human cancer. Int. J. Cancer 106: 806-811.

Hohmeier, H. E., H. Mulder, G. Chen et al. 2000. Isolation of INS-1-derived cell lines with robust ATP-sensitive K+ channel-dependent and -independent glucose-stimulated insulin secretion. Diabetes 49: 424-430. Full Text

Holz, G. G. 2004. Epac: A new cAMP-binding protein in support of glucagon-like peptide-1 receptor-mediated signal transduction in the pancreatic beta cell. Diabetes 53: 5-13.

Hui, H., C. Wright & R. Perfetti. 2001. Glucagon-like peptide 1 induces differentiation of islet duodenal homeobox-1: positive pancreatic ductal cells into insulin-secreting cells. Diabetes 50: 785-796. Full Text

Kim, J. G., L. L. Baggio, D. P. Bridon et al. 2003. Development and characterization of a glucagon-like peptide 1-albumin conjugate: the ability to activate the glucagon-like peptide 1 receptor in vivo. Diabetes 52: 751-759. Full Text

Lieberman, S. M., A. M. Evans, B. Han et al. 2003. Identification of the beta-cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes. Proc. Natl. Acad. Sci. (USA) 100: 8384-8388. Full Text

Lu, D., H. Mulder, P. Zhao, et al. 2002. 13C NMR isotopomer analysis reveals a connection between pyruvate cycling and glucose-stimulated insulin secretion (GSIS). Proc. Natl. Acad. Sci. (USA) 99: 2708-2713. Full Text

Moore, A., P. Z. Sun, D. Cory et al. 2002. MRI of insulitis in autoimmune diabetes. Magn. Res. Med. 47: 751-758.

Moore, A., S. Bonner-Weir & R. Weissleder. 2001. Noninvasive in vivo measurement of beta-cell mass in mouse model of diabetes. Diabetes 50: 2231-2236. Full Text

Moore, A., J. Grimm, B. Han & P. Santamaria. 2003. Tracking the recruitment of diabetogenic CD8+ T cells to the pancreas in real time. Diabetes (in press).

Parmee, E. R., H. Jiafang, A. Mastracchio et al. 2004. 4-Amino cyclohexylglycine analogues as potent dipeptidyl peptidase IV inhibitors. Bioorgan. Med. Chem. Lett. 14: 43-46 Full Text [PDF 168 KB]

Pospisilik, J. A., J. A. Ehses, T. Doty et al. 2003. Dipeptidyl peptidase IV inhibitor treatment stimulates beta-cell survival and islet neogenesis in streptozotocin-induced diabetic rats. Diabetes 52: 741-750.

Reimer, M. K., J. J. Holst & B. Ahr?n. 2002. Long-term inhibition of dipeptidyl peptidase IV improves glucose tolerance and preserves islet function in mice. Eur. J. Endocrinol. 46: 717-727. Full Text [PDF 202 KB]

Scrocchi, L. A., M. E. Hill, J. Saleh et al. 2000. Elimination of glucagon-like peptide 1R signaling does not modify weight gain and islet adaptation in mice with combined disruption of leptin and GLP-1 action. Diabetes 49: 1552-1560.

Stoffers, D. A., T. J. Kieffer, M. A. Hussain et al. 2000. Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas. Diabetes 49: 741-748.

Taylor, R. 2004. Causation of type 2 diabetes: the gordian knot unravels. N. Engl. J. Med. 350: 639-641.

Tran V., V. G. Chen, C. B. Newgard & H. E. Hohmeier. 2003. Discrete and complementary mechanisms of protection of beta cells against cytokine-induced and oxidative damage achieved by Bcl-2 overexpression and a cytokine selection strategy. Diabetes 52: 1423-1432. Full Text

Villhauer, E. B., J. A. Brinkman, G. B. Nader et al. 2003. 1-[[(3-Hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J. Med. Chem. 46: 2774-2789. Full Text [PDF 230 KB]

Villhauer, E. B., J. A. Brinkman, G. B. Nader et al. 2002. 1-[2[(5-Cyanopyridin-2-yl)amino]-ethylamino]acetyl-2-(S)-pyrrolidine-carbonitrile: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J. Med. Chem. 45: 2362-2365. Full Text [PDF 59 KB]

Zander, M., S. Madsbad, J. L. Madsen & J. J. Holst. 2002. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 359: 824-830.

Organizers

Judith L. Treadway, PhD

Pfizer Global Research & Development
email | publications

John R. Wetterau, PhD

email | publications

Keynote Speaker

Christopher B. Newgard, PhD

Duke University Medical Center
Sarah W. Stedman Nutrition and Metabolism Center
email | web site | publications

Christopher B. Newgard is director of the Sarah W. Stedman Nutrition and Metabolism Center and a professor at the departments of pharmacology and cancer biology, biochemistry, and internal medicine at Duke University Medical Center. Newgard holds a PhD in biochemistry from the University of Texas Southwestern Medical Center and has had a distinguished and productive research career. In 2001 he was given the Outstanding Scientific Achievement Award by the American Diabetes Association, and he has received multiple other honorary scientific distinctions in this career.

Newgard has served on the Grant Review Board of the American Diabetes Association and worked for the NIH in the metabolism study division for several years. His papers have been published in the Proceedings of the National Academy of Sciences, Nature Medicine, Diabetes, and many other publications.

Speakers

Susan Bonner-Weir, PhD

Harvard Medical School
Joslin Diabetes Center
email | web site | publications

Susan Bonner-Weir is senior investigator at the Joslin Diabetes Center and associate professor of medicine at Harvard Medical School. Her major area of interest for over 25 years has been the endocrine pancreas. With a series of rodent models, she and her colleagues have provided compelling evidence that adult pancreatic beta-cell mass increases in response to metabolic needs. They have also been examining the mechanisms of postnatal pancreatic growth.

Bonner-Weir graduated from Rice University and received her PhD in biology from Case Western Reserve University. She has published over 120 peer-reviewed papers and has served on the research grant review panels for the NIH and American Diabetes Association, as well as on numerous editorial boards, including those of Endocrinology, American Journal of Physiology, Diabetes, and Cell Transplantation.

Daniel J. Drucker, MD

University of Toronto
Banting and Best Diabetes Centre
email | web site | publications

Daniel J. Drucker works as a physician at Toronto General Hospital and is currently a professor of medicine in the division of endocrinology at the University of Toronto. He also serves as the director of the Banting and Best Diabetes Centre in Toronto. Drucker received his MD from the University of Toronto in 1980 and pursed an internship in medicine at Johns Hopkins Hospital. Under the supervision of Joel Habener, he was a postdoctoral research fellow in the molecular endocrinology at the Massachusetts General Hospital for three years.

Drucker's laboratory currently studies the molecular biology and physiology of the glucagons-like-peptides with a focus on the potential therapeutic role of GLP-1 and GLP-2 in the treatment of diabetes. He serves on the editorial boards of Diabetes, Molecular Endocrinology, and the American Journal of Physiology, and he is the recipient of the distinguished investigator award of the Canadian Diabetes Association.

Thomas E. Hughes, PhD

Novartis Institute for BioMedical Research
email | web site | publications

Thomas E. Hughes currently spearheads diabetes and metabolism research at the Novartis Institutes for BioMedical Research in Cambridge, MA. He directs the development of a technology platform to enable rapid evaluation of novel targets and predictive biomarkers to accelerate the discovery of new compounds of potential therapeutic value.

Prior to his current position, Hughes served as the executive director of pharmacology in the area of cardiovascular diseases at Novartis, where he initiated and oversaw the dipeptidyl peptidase IV (DPP4) inhibitor program. In recognition of his leadership in this program, he was honored with the Novartis Distinguished Scientist Award in 2000 and the 2004 Novartis Chairman's Leadership Excellence Award for Innovation. He received a PhD in nutrition from Tufts University and has served as an adjunct faculty member at the UMDNJ-Robert Wood Johnson Medical School's department of molecular genetics and microbiology.

Anna Moore, PhD

Harvard Medical School
Massachusetts General Hospital
email | publications

Anna Moore is an assistant professor of radiology in cell biology at the Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School. She received her PhD from the Institute of Biochemistry at the Russian Academy of Sciences in 1990. Her postdoctoral research took her to the United States, where she focused on cell biology as a fellow at the Webster Center for Biological Science at Amherst College, followed by a four-year fellowship at the department of radiology at MGH, where she is currently investigating into noninvasive imaging techniques of the pancreatic tissues.

Moore received the Junior Faculty Award from the American Diabetes Association for her investigations into in vivo MR imaging of insulitis in autoimmune diabetes. She is the author of many publications on noninvasive imaging of the pancreas, including in the journals Cancer Research, Diabetes, and Radiology.