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