DIABETES/METABOLISM RESEARCH AND REVIEWS REVIEW ARTICLE Diabetes Metab Res Rev 2003; 19: 32–42. Published online 17 October 2002 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/dmrr.331 Gene expression profiling in islet biology and diabetes research Ernesto Bernal-Mizrachi Corentin Cras-M´ eneur Mitsuru Ohsugi M. Alan Permutt* Washington University School of Medicine, Division of Endocrinology, Diabetes and Metabolism, St. Louis, Missouri, USA *Correspondence to: M. Alan Permutt, M.D. Washington University School of Medicine Division of Endocrinology, Diabetes and Metabolism, 660 S. Euclid Avenue, Campus Box 8127, Saint Louis, MO 63110. E-mail: apermutt@im.wustl.edu Received: 6 June 2002 Accepted: 26 August 2002 Summary Following the sequencing of most of the human and mouse genomes, the next task for physicians and scientists will be to assess the relative levels of expression of these genes during development, following exposure to various nutritional and pharmacological conditions, and in disease states such as diabetes and related metabolic disorders. This review provides an overview of the various methodologies available for monitoring global gene expression. Use of cDNA libraries, Expressed Sequence Tag (EST) sequencing projects and databases, differential display (DD), serial analysis of gene expression (SAGE), subtractive cloning, and both cDNA and oligo microarrays are discussed, along with their merits and limitations. The Endocrine Pancreas Consortium http://www.cbil.upenn.edu/EPConDB/ has constructed mouse and human cDNA libraries from adult and various stages of embryonic development of endocrine pancreas. Over 100 000 ESTs have been deposited in public databases, and each clone is available through the IMAGE Consortium. A guide to Internet access is provided for future investigation. Copyright  2002 John Wiley & Sons, Ltd. Keywords cDNA library; SAGE; microarray; gene expression profile; endocrine pancreas consortium Introduction The discovery of the insulin gene, one of the first mammalian genes to be cloned, became an important part of biomedical history in 1977 [1]. Later the insulin-receptor gene was cloned in 1989 [2], followed shortly thereafter with the cloning of the glucokinase [3] and glucose-transporter genes [4]. Early diabetes/metabolic related gene-expression studies examined one or a few genes. At present, numerous genes have been identified in pancreatic islets and other metabolic tissues. For example, a survey of islet publications from the year 2001 to the present listed many studies describing a host of islet- transcription factors along with their effects on pancreatic islet development and function (e.g. PDX, HNF1α, HNF4α, HNF4γ , HNF3β , HNF3γ , lmx1b, Nkx2.2, Nkx6.1, Neuro-D/Beta2, Neurogenin 3, Pax 4 and Pax 6, PPARα and PPARγ , c-Myc, c-Fos, Egr-1, Egr-2, Elk-1, SRF-1, CREB, NF-κ B, SMADs 1,2, and 4, HES-1, C/EBP, Id-1 and Id-3, RIPE3b1, and PBX, see Reference [5] for review). With the completion of the sequencing of the human genome, we now know of the existence of more than 30 000 genes. Analysis of expression of these genes has become a major focus of genome research, and for diabetes research in particular, the profiles of gene expression in critical tissues is of primary importance. Gene expression studies for diseases such as diabetes will be challenging, as they must encompass various stages of embryonic development, different physiological and nutritional conditions, changes throughout the evolution of Copyright  2002 John Wiley & Sons, Ltd.