Review Articles in 2010

Circadian rhythms make a critical contribution to endocrine functions that involve adipose tissue at the systemic, organ and stem cell levels. This Review examines the data that link circadian biology to adipose tissue and its related metabolic organs, such as the liver and pancreas. These findings might affect clinical practice in the coming years.

The relationships between fetal cell microchimerism and human physiology and pathology represent an interesting and novel research field. This Review provides an overview of the role of fetal microchimeric cells in autoimmune and nonautoimmune diseases. Moreover, the mechanisms by which fetal cell microchimerism is believed to modulate the protection against cancer or tumor progression will be discussed, together with future research directions.

This Review summarizes the role of reactive oxygen species and oxidative stress in diabetes mellitus and in the pathogenesis of endothelial cell dysfunction and diabetic nephropathy. Furthermore, the authors explore possible therapeutic interventions to reduce oxidative stress and endothelial cell dysfunction and retard the progression of diabetic nephropathy.

Research into ciliopathies could cast new light on endocrine signaling pathways, which might lead to the development of novel treatments for patients with obesity and type 2 diabetes mellitus. This Review discusses how research into the extremely rare Alström syndrome could provide insights into the cellular pathways that are important in insulin secretion and other endocrine functions.

Stress is a state of physiological or psychological strain caused by adverse stimuli. Prostaglandin E₂ (PGE₂), acting through its four receptor subtypes (EP1, EP2, EP3, and EP4), is involved in stress responses. This Review discusses how PGE₂orchestrates a range of stress responses via the EPs.

The treatment of testicular germ cell tumors has been called one of the success stories of modern medicine, with sustained response to treatment in >90% of cases, regardless of clinical stage. This Review discusses pathology, diagnostic procedures and treatment of testicular germ cell tumors, and highlights the importance of individual therapeutic management within a multidisciplinary approach according to the risk of short-term and long-term toxic effects.

This Review describes the process of positive and negative selection of developing T cells in the thymus and the role of the autoimmune regulator (AIRE) in the presentation of tissue-restricted antigens. Furthermore, it addresses how mutations of this gene lead to the failure to eliminate autoreactive T cells, which can lead to clinical autoimmune syndromes.

Bisphosphonate-associated osteonecrosis (BON) is a rare complication that almost exclusively affects the jaws. BON has only been recognized within the past 10 years; therefore, management strategies for patients with BON are poorly defined. In this Review the authors discuss the pathobiology, diagnosis, presentation, incidence and prevalence of BON, as well as highlighting risk factors and tumor types associated with this complication.

Genetic and molecular research has improved our understanding of the mechanisms underlying lipodystrophy, a disorder characterized by complete or partial loss of adipose tissue. This Review describes the various types of lipodystrophy syndromes known to date, as well as mechanisms responsible for concomitant metabolic abnormalities, and provides a perspective on current treatment options and novel therapeutic approaches, with a focus on the adipokines leptin and adiponectin.

Although decreased bone mass and osteopenia are common complications of autoimmune diseases, the mechanisms that explain the bone loss are diverse. This Review discusses the multiple faces of autoimmune-induced bone loss—from the direct destruction of bone by inflammation, as observed in rheumatoid arthritis, to the less-characterized potential perturbation of metabolic pathways that systematically control bone mass in type 1 diabetes mellitus or autoimmune thyroid diseases.

The findings from the DCCT–EDIC and UKPDS epidemiological studies suggest that early exposure to hyperglycemia predisposes individuals to the development of diabetic complications, a phenomenon referred to as metabolic memory or the legacy effect. Transient exposure to hyperglycemia results in long-lasting epigenetic modifications that lead to changes in chromatin structure and gene expression, resulting in vascular dysfunction.

Glycogen storage disease type I (GSD-I) consists of a group of autosomal recessive disorders that cause metabolic abnormalities and/or myeloid dysfunction. This Review addresses the etiology of GSD-Ia and GSD-Ib and of glucose-6-phosphatase-β deficiency and highlights advances in diagnosis and treatment, including transplantation and gene therapy.

Growth hormone, insulin-like growth factor I and insulin have potent growth-promoting and anabolic actions. Their potential involvement in tumor promotion and progression has been of concern for several decades. In this Review Peter Clayton and colleagues examine the complex evidence regarding growth hormone, the insulin-like growth factor axis, insulin and cancer risk.

The diabetogenic effect of glucagon has long overshadowed the potential of this pancreatic hormone as an endogenous satiety and anti-obesity factor. This Review discusses the role of glucagon as a beneficial endocrine factor in lipid and energy metabolism and its potential as a therapeutic agent on the basis of studies that combine the agonism of glucagon receptor and glucagon-like peptide 1 receptor.

The prognosis of patients with childhood craniopharyngioma is impaired owing to the vicinity of the tumor to the optic tract and to pituitary and hypothalamic areas. Long-term sequelae after treatment—notably severe hypothalamic obesity—negatively effect patients' quality of life. This Review discusses risk-adapted treatment strategies that aim to improve prognosis and prevent sequelae.

This Review addresses the pharmacology and physiology of aspirin use and how it may differ in patients with diabetes mellitus. The clinical trial evidence for the primary prevention of cardiovascular disease with aspirin therapy in patients with diabetes mellitus will then be examined in light of these potential mechanisms. Finally, suggestions for clinical practice are provided, and the limitations in current evidence as well as the upcoming trials that may help resolve these important clinical issues are highlighted.

Isolated growth hormone deficiency is the most common pituitary hormone deficiency and can originate from congenital or acquired causes, although the majority of cases are idiopathic. This Review summarizes currently available evidence on the genetic factors involved in isolated growth hormone deficiency, and highlights diagnostic challenges and novel advances in treatment.

Clinical manifestations of hypovitaminosis D, a highly prevalent disorder worldwide, include musculoskeletal disorders as well as nonclassical manifestations, such as increased risk of respiratory infections, diabetes mellitus and possibly cardiovascular diseases. This Review discusses the prevalence of hypovitaminosis D across the lifecycle, and risk factors and health outcomes associated with it in developing countries.

With the growing epidemic of obesity, the number of bariatric surgeries in adolescent patients has continuously increased over the past years. This Review addresses the indications for and against bariatric surgery in adolescents, as well as currently available evidence on clinical outcomes, and summarizes measures to provide adequate postoperative care in this patient population.

This Review focuses on new findings regarding the role of peroxisome proliferator-activated receptor γ (PPARγ) in adipose tissue and skeletal metabolism and summarizes the emerging role of PPARγ as an integral part of a complex circadian regulatory system that modulates food storage, energy consumption and skeletal metabolism.