Volume 12 Issue 1, January 2006

Current rules forbid even legitimate research, critics say.

Woo-Suk Hwang's research is under investigation.

Researchers are injecting stem cells to treat diseases.

Violating the so-called voluntary rules could result in stiff penalties.

CDC staff say the reorganization is a change for the worse.

Lawsuit alleges that at least five people have died in illegal trials.

NIH scientists join forces to tackle internal problems.

Three years after scientists declared estrogen harmful to the heart, some say the hormone was unfairly maligned. Apoorva Mandavilli finds out why it's time to reopen the debate.

Chicago octogenarian Janet Rowley has always strived to balance a stellar research career with the needs of her family. Even working only part time for more than 20 years, she was the first to discover that chromosome translocations can trigger cancer.

Cytokines secreted during tissue damage and inflammation can trigger the formation of fibrous tissue. The cytokine IL-13 is now shown to induce TGF-β, the major fibrotic cytokine. IL-13 does so through a receptor previously thought to relay no signal (pages 99–106).

A cancer genetics dogma states that hematologic malignancies arise as a result of defined chromosomal translocations, whereas mutations underlie epithelial solid tumors. This rule is now broken in an analysis of chromosomal translocations in prostate cancer.

Changes in blood flow and hypoxia lead to endothelial-mediated control of vascular tone. An additional nucleotide receptor on endothelial cells has been identified that mediates release of nitric oxide and vasodilation (pages 133–137).

In people with Parkinson disease, neurons in certain brain regions are more likely to die than others. A potassium channel may be the key to understanding this differential neuronal death.

A single enzyme is responsible for antibiotic resistance to two very different drugs (pages 83–88).

Defects in the ability of fat cells to transport glucose are linked to insulin resistance in muscle and liver. Retinol binding protein 4 (RBP4) now comes to the fore as a new adipokine, linking glucose uptake in adipocytes with systemic insulin sensitivity.

The interplay of factors that impair insulin signaling to cause type 2 diabetes is unclear, but one idea is that visceral fat might produce them. Visfatin, a protein previously known for its effect on immune cells, may be one of these factors.

Liver glucose production is crucial to survival during fast and is abnormally elevated in diabetes. Studies of the transcriptional coactivator Torc2 redefine the mechanism by which cAMP signaling affects fasting-induced glucogenesis.

Sirt1, an enzyme that removes acetyl groups from specific nuclear proteins, has been linked to the regulation of aging. It is now clear that Sirt1 also controls hepatic glucose metabolism by serving as a sensor of the metabolic status in hepatocytes.

Insulin secretion regulates glucose homeostasis and its dysregulation causes type 2 diabetes. Short noncoding microRNAs have now been shown to control exocytosis, the final event in insulin secretion. This discovery opens potential perspectives for diabetes therapy.

The transcriptional network downstream of the insulin receptor is incompletely understood, but recent data identify a new player. Foxa2—a forkhead transcription factor—controls hepatic lipid metabolism in fasting and type 2 diabetes, improving insulin resistance in peripheral tissues.

Comparing gene expression patterns of pancreatic islets from normal and diabetic people show that the transcription factor ARNT/HIF1β is the most markedly reduced in humans with the disease. ARNT regulates many beta-cell genes, insulin secretion and glucose tolerance.

Obesity-related chronic inflammation underlies insulin resistance, a key feature of type 2 diabetes. Recent data link the stress pathway of the endoplasmic reticulum to this phenomenon.

Primary alterations in insulin signaling pathways are not the only way to reduce the body's sensitivity to insulin. By promoting the release of cytokines, liver inflammation can also lead to insulin resistance.

A reduction in mitochondrial activity and the subsequent decrease in energy expenditure contribute substantially to metabolic dysfunction in aging, insulin resistance and diabetes. Enhancing mitochondrial activity could improve metabolic homeostasis.

'Survival of the fittest' is based in part on the notion that genetic selection allows individuals to escape predators in the wild. A recent study indicates that selection for increased aerobic capacity may afford protection from cardiovascular risk factors associated with the metabolic syndrome.

A spate of recent studies has identified key neural pathways that control glucose production from the liver. They may provide a new link between obesity and type 2 diabetes.

AMP-activated protein kinase has a crucial role in coupling substrate availability with substrate oxidation in skeletal muscle. Recent findings suggest that this biochecmical fuel sensor also participates in the hypothalmic recognition of the body's energy status.

The influence of hormones on the development of brain circuits has long been recognized. A recent study shows that leptin has a similar effect on the emergence of feeding pathways. There might therefore be a crucial window during which a subject's basal metabolic phenotype can be altered.

Circadian control depends on oscillating transcription factors, master switches synchronized by stimuli such as light and feeding. Recent studies show that altering circadian rhythmicity also results in pathophysiological changes resembling the metabolic syndrome.

Insulin resistance can be good for your health when it is caused by klotho, a hormone that prolongs life. A reduction in insulin-stimulated intracellular glucose availability may prevent intracellular lipid overload and lipotoxicity, a proposed mechanism of hte life-shortening metabolic syndrome.

Overweight and obesity, the main drivers of type 2 diabetes, have long been regarded as health risks associated with affluence. Over the last decade, profound changes in the quality, quantity and source of food consumed in many developing countries, combined with a decrease in levels of physical activity among the population, have led to an increase in the prevalence of diabetes and its complications. Here, we present quantitative estimates of the epidemiological and economic impact of obesity and diabetes on developing countries. We provide the economic rationale for public policy action. We stress the importance of creating a roadmap to guide the development of comprehensive policies involving governments and private companies, and emphasize the need for experimentation in building the evidence while testing theories.

Obesity and type 2 diabetes are urgent and extraordinarily complex health problems. The US National Institutes of Health (NIH) thus supports a broad and vigorous portfolio of research aimed toward developing effective strategies for prevention and treatment, and building the scientific evidence base for public policy decisions. Much of this research stems from the creativity of individual investigators. Above and beyond these studies, the NIH uses a variety of mechanisms, in consultation with external scientific and lay communities, to foster research in emerging disciplines, encourage new collaborative efforts and promote research translation from basic discoveries to clinical trials (from bench to bedside) and from clinical trials to medical practice and community awareness (from bedside to practice). These efforts encompass extensive research on obesity's many devastating comorbidities in addition to type 2 diabetes: cardiovascular disease (CVD), cancer, nonalcoholic steatohepatitis and other diseases and disorders. Given the topic of this month's special content, however, this Commentary focuses on obesity and diabetes, including CVD research associated with both.

It is astonishing that, in our times, a noncommunicable disease should have acquired the cursed label of pandemic, yet such is the situation for diabetes. The numbers speak for themselves, with up to 200 million people worldwide currently suffering from the disease and the prediction that this number will double by the year 2025. In addition to the decreased life expectancy and lower quality of life of individuals with diabetes, the disease and its associated complications are a major burden on national budgets.

Medical services in Japan are public. This health system ensures free access to medical facilities for all Japanese citizens under universal insurance coverage and, as a result, the life expectancy of the Japanese population has become the world's longest (mean, 81.8 years). The cost of medical services now accounts for 7.7% of the gross domestic product of Japan, and is the second lowest in the developed world, after the UK. In 2000, the World Health Organization ranked Japan's medical services as the most efficient in the world.

What makes the metabolic syndrome field tick? Discover the recent papers with the most impact in the discipline and find out the funding priorities of countries interested in this problem.