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Research Summary
Diabetes, insulin action, pancreatic endocrine stem cells, genetics
Research Activities
Dr. Accili’s research is focused on the pathogenesis of insulin resistance and its role in type 2 diabetes. Emphasis is placed on the development of ”designer” mice with mutations affecting insulin action and pancreatic development, with a specific interest in the identification of islet stem cells for use in beta cell replacement therapies. Current interests include forkhead transcription factors in insulin action, and especially in linking peripheral insulin action and b-cell function. Accili’s lab has recently shown that b-cell failure in mice is reversed by haploinsufficiency for the forkhead transcription factor Foxo1 through partial restoration of b-cell proliferation and increased expression of the pancreatic transcription factor Pdx1. Forkhead is also emerging as the insulin-regulated transcription factor that regulates glucose-6-phosphatase, a key enzyme in the pathogenesis of diabetes. Moreover, his laboratory is interested in examining the role of different tissues in insulin action and the pathogenesis of insulin resistance. Accili’s lab was the first to draw attention to the apparent paradox that impairment of insulin action in skeletal muscle is not sufficient to set in motion the complex metabolic abnormalities that eventuate in type 2 diabetes. Using transgenic rescue of insulin receptor-deficient mice, Accili’s lab has recently shown that insulin action in liver, brain and b-cells is sufficient to confer insulin sensitivity onto the whole organism and protect against the development of diabetes in mice.
Positions & Appointments
| 1999-present |
Professor, Department of Medicine |
Columbia University Medical Center |
New York, NY |
| 1999-2000 |
Head, Diabetes Research Unit, Division of Endocrinology, Department of Medicine |
Columbia University College of Physicians & Surgeons |
New York, NY |
| 1996-1999 |
Chief, Unit on Genetics and Hormone Action, Developmental Endocrinology Branch |
NICHD, National Institutes of Health |
Bethesda, MD |
| 1990-1995 |
Visiting Scientist, Diabetes Branch |
NIDDK, National Institutes of Health |
Bethesda, MD |
| 1987-1990 |
Assistant Professor, Department of Internal Medicine |
University of Rome- Tor Vergata School of Medicine |
Rome, Italy |
Education and Training
| 1983 |
M.D. |
University of Rome School of Medicine, Rome, Italy |
| 1983-1985 |
Intern and Resident, Department of Internal Medicine |
University Hospital "A. Gemelli", Rome, Italy |
| 1985-1988 |
Fogarty Fellow, Diabetes Branch |
NIDDK, National Institutes of Health, Bethesda, MD |
Honors and Awards
1994 Chafic Haddad Memorial Lectureship, Middle East Medical Association
1995-1997 Visiting Professor, University of Ancona Medical School, Ancona, Italy
1996 Roberto De Pirro Memorial Lecture, VI International Symposium on Insulin Receptors and Insulin Action
Committees and Society Memberships
American Diabetes Association
Endocrine Society
American Society for Biochemistry and Molecular Biology
Associate Member of the Italian Diabetes Society
Special Interests
Molecular genetics of type 2 diabetes, Insulin action, and Development of pancreas
Favorite Websites
http://www.ncbi.nlm.nih.gov/
http://cpmcnet.columbia.edu/library/elist.html
http://gdbwww.gdb.org
http://www.cidr.jhmi.edu
This is an exciting time for diabetes research. Our laboratory is by the National Institutes of Health and the Juvenile Diabetes Foundation International to study the genetics and pathophysiology of this complex disease at several levels. Currently, we are developing ìdesignerî mice with targeted gene mutations to understand insulin signaling mechanisms in different tissues, to dissect the contribution of insulin and insulin-like growth factors to the development of endocrine and exocrine pancreas, and to characterize transcription factors that regulate insulin effects on glucose production and beta cell function. We are an interactive team of physicians and scientists that want to partake in the diabetes challenge. We are always looking for a few good men and women who want to share the excitement of our laboratory experience. If you have what it takes, write or visit us, on the web or in our new research building!
Selected Publications:
1. Okamoto H, Nakae J, Kitamura T, Park BC, Dragatsis I, Accili D. (2004) Transgenic rescue of insulin receptor-deficient mice. J Clin Invest
114(2):214-23
2. Accili D. (2004) Lilly lecture 2003: the struggle for mastery in insulin action: from triumvirate to republic. Diabetes
53(7):1633-42
3. Accili D, Menghi G, Bonacucina G, Martino PD, Palmieri GF. (2004) Mucoadhesion dependence of pharmaceutical polymers on mucosa characteristics. Eur J Pharm Sci
22(4):225-34
4. Accili D, Arden KC. (2004) FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell
117(4):421-6
5. Tsuchida A, Yamauchi T, Ito Y, Hada Y, Maki T, Takekawa S, Kamon J, Kobayashi M, Suzuki R, Hara K, Kubota N, Terauchi Y, Froguel P, Nakae J, Kasuga M, Accili D, Tobe K, Ueki K, Nagai R, Kadowaki T. (2004) Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity. J Biol Chem
279(29):30817-22
6. Nandi A, Kitamura Y, Kahn CR, Accili D. (2004) Mouse models of insulin resistance. Physiol Rev
84(2):623-47
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