Editorial
Novel Factors in the Regulation of β-Cell Function
- Christian Boitard1,
- Erol Cerasi2,
- Suad Efendic3,
- Jean-Claude Henquin4,
- Donald F. Steiner5 and
- Ele Ferrannini6
- 1INSERM U342, St. Vincent de Paul Hospital, Paris, France
- 2Department of Endocrinology & Metabolism, Hebrew University Hadassah Medical Center, Jerusalem, Israel
- 3Department of Molecular Medicine, Division of Endocrinology & Diabetes, Karolinska Hospital, Stockholm, Sweden
- 4Department of Physiology, Endocrinology-Metabolism, Université Catholique de Louvain, Brussels, Belgium
- 5Department of Biochemistry and Molecular Biology, and Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois
- 6Metabolism Unit, CNR Institute of Clinical Physiology, University of Pisa, Pisa, Italy
- Address correspondence and reprint requests to E. Ferrannini, MD, Department of Internal Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy. E-mail: ferranni{at}ifc.cnr.it
- ASP, acylation-stimulating protein
- FFA, free fatty acid
- mtD, mitochondrial diabetes
- PKG, protein kinase G
- PLA2, phospholipase A2
- PPAR, peroxisome proliferator-activated receptor
- QTL, quantitative trait locus
- ROS, reactive oxygen species
- RXR, retinoid X receptor
- SNP, single nucleotide polymorphism
- UCP, uncoupling protein
Insulin secretion and β-cell biology are the focus of the Servier-IGIS Symposia that have been held yearly since 2000 in St. Jean Cap Ferrat in southern France (1). This volume, the fourth of a series published in Diabetes (1–3), collects the proceedings of the fourth Servier-IGIS Symposium, which focused on novel factors involved in islet biology and β-cell function. Special emphasis was placed on nuclear receptors, new genes that are associated with type 2 diabetes, and the role of mitochondria and lipid modulators in islet function. This symposium offers a striking example of how better knowledge of β-cell biology and the introduction of genetic tools to explore the pathophysiology of type 2 diabetes complement each other to improve our understanding of glucose homeostasis.
Section I details the role of nuclear receptors in islet function, with special emphasis on peroxisome proliferator-activated receptors (PPARs). PPARα was cloned in 1990; related receptors were subsequently cloned, namely PPARδ (or β) and PPARγ. They form heterodimers with retinoid X receptor (RXR); their natural ligands are fatty acids and lipid-derived substrates. These receptors are major regulators of lipid metabolism, linking availability of glucose and lipids and long-term metabolic adaptation. Most importantly, they are targeted by key drugs used in treatment of hyperlipidemias and diabetes, namely fibrates and thiazolidinediones. Thiazolidinediones are synthetic PPARγ agonists developed to improve glucose tolerance by enhancing insulin sensitivity and restoring β-cell function. Patients with dominant-negative PPARγ mutations develop severe hyperglycemia, and PPARγ gene variants have been associated with type 2 diabetes. Besides the many actions of PPARγ agonists on the transcription of genes controlling insulin sensitivity in adipose tissue, they increase glucose sensing in liver and in β-cells. In the latter, PPARγ also enhances growth and prevents apoptosis.
PPARα (the target of fibrates) controls lipid uptake and oxidation …
