Editorial

This issue of CDR contains a range of interesting, well-crafted and insightful reviews on diabetes mellitus and its complications by highly respected groups of investigators. At the level of the pancreatic acinar cells, Bouwens examines the ability of beta cells to regenerate, and considers recent data such as the use of combinations of growth factors to promote regeneration or replacement by precursor cell neogenesis, which may eventually contribute to a therapeutic approach to insulindependent diabetes. Kim et al. reviews research on the transcriptional regulation of glucose sensors (GLUT2 and glucokinase) in beta cells and liver and the potential role for these mechanisms in the development of insulin resistance in type 2 diabetes. Two papers examine the links between obesity, insulin resistance, pro-inflammatory changes and cardiovascular disease in type 2 diabetes. Bulcao et al. review patterns of cytokine production by adipose tissue, including adiponectin and leptin, which promote insulin sensitivity and other cytokines such as tumor necrosis factor alpha that promote to proinflammatory changes and insulin resistance. You and Nicklas focus on the beneficial consequences of lifestyle modifications to cause weight loss and their effects on inflammatory changes and adipose tissue pro- and anti-inflammatory cytokine production. A broadly related review by Garcia-Romero and Escobar-Morreale considers the relation between polycystic ovary syndrome, insulin resistance and compensatory hyperinsulinemia, and hyperandrogen disorders in women with type 2 diabetes. They also examine the notion that insulin resistance and hyperinsulinemia resulting from insulin injection are important in the development of hyperandrogenism in type 1 diabetes. For these women, the combination of hyperandrogenism and insulin resistance exacerbates cardiovascular risk. The important vascular actions of insulin, and their potential consequences for diabetic complications, are considered. Duncan et al., review the effects of insulin on vascular endothelium, with particular regard to insulin signaling and the endothelial nitric oxide (NO) system. For macrovascular function, insulin-stimulated NO production has an antiatherogenic effect, however, insulin resistance reveals adverse effects; NO production is reduced and the proatherogenic effects may be apparent, possibly stimulated by activation of MAPkinase cascades, endothelin production and reactive oxygen species. Rattigan et al address the hemodynamic and metabolic effects of insulin in skeletal muscle, particularly in terms of microvascular effects, capillary recruitment and the role of the NO and endothelin systems. The potentially important causative relationship between vascular factors and insulin resistance is reviewed. This issue contains two papers on diabetic retinopathy. Simo et al. critically review the changes in angiogenic and antiangiogenic factors that are important in the etiology and control of proliferative retinopathy. The former include vascular endothelial growth factor, insulin-like growth factor, and the latter, which may have therapeutic implications, include pigment epithelium derived factor and somatostatin. Gomez-Ulla et al. examine the problem of diabetic macular edema, with particular regard to therapeutic application by intravital injection of the anti-inflammatory glucocorticosteroid, triamcinolone, emphasizing safety and efficacy data. Finally, De Block et al. consider the important problem of diabetic gastroporesis, which has a 30-50% prevalence in patients with type 1 or type 2 diabetes. They review current understanding of gastroporesis, including epidemiology, diagnosis, clinical consequences, the roles of potential mechanisms such as autonomic neuropathy, hyperglycemia, and altered gastrointestinal neuropeptides, as well as current therapeutic approaches. I hope readers find these reviews as stimulating, informative and enjoyable as I did.