Editorial
Toward a Systems Biology of Insulin Secretion and Type 2 Diabetes
- Donald F. Steiner1,
- Christian Boitard2,
- Erol Cerasi3,
- Suad Efendic4,
- Jean-Claude Henquin5 and
- Ele Ferrannini6
- 1Departments of Biochemistry and Medicine, University of Chicago, Chicago, Illinois
- 2Institut National de la Santé et de la Recherche Médicale U561, St. Vincent de Paul Hospital, Paris, France
- 3Department of Endocrinology and Metabolism, Hebrew University Hadassah Medical Center, Jerusalem, Israel
- 4Department of Molecular Medicine, Division of Endocrinology & Diabetes, Karolinska Hospital, Stockholm, Sweden
- 5Unit of Endocrinology and Metabolism, University of Louvain, Brussels, Belgium
- 6Metabolism Unit, CNR Institute of Clinical Physiology, University of Pisa, Pisa, Italy
- Address correspondence and reprint requests to Donald F. Steiner. E-mail: dfsteine{at}midway.uchicago.edu
- CNS, central nervous system
- FFA, free fatty acid
- FFAR, free fatty acid receptor
- GBS, gastric bypass surgery
- GIP, gastric inhibitory polypeptide
- GLP, glucagon-like peptide
- HGP, hepatic glucose production
- IL, interleukin
- KATP channel, ATP-sensitive K+ channel
Although it is clear that β-cell pathology, in particular disordered insulin secretion, is a key underlying pathogenetic feature of most forms of diabetes, complex interactions of the islets with other organs, such as brain, liver, gut, and several peripheral tissues, are also essential for the normal integration of metabolism. It is this area that has been explored in the Seventh Annual Servier-IGIS Meeting, which was held last Spring in St. Jean Cap Ferrat in Southern France. The focus of these meetings, since their inception in 2000, has been the β-cell and the mechanisms underlying its development and function as the source of insulin, the most essential regulator of the blood glucose level.
The familiar pathways of glucose, lipid, and amino acid metabolism in humans and other mammals are, of course, fundamental to almost all organisms, except perhaps for the most highly specialized bacteria, so it is not surprising that insulin-like molecules and the insulin/IGF receptor signaling system are well conserved features of all metazoans that have been studied. With the rise of multicellular organisms in evolution came the need to regulate and coordinate metabolism and growth in order to maintain both the constancy of the internal environment (homeostasis) and also to respond to the external environment. One of the most prominent environmental stimuli had to be the availability of nutrients and fuels for survival and growth. The insulin-like hormones, insulin and IGF, appear to have evolved, along with a panoply of other regulatory substances, to fine-tune the efficient uptake, storage, and utilization of nutrients for either energy production or growth.
Appropriately, the symposium opened with an introductory lecture by Leopold, reviewing our current knowledge of the control of metabolism and growth in the fruit fly, Drosophila melanogaster, by insulin-like peptides and an insulin signaling pathway that is remarkably similar …
