UCSD Researchers Find Protein That Triggers Diabetes

Posted by Alexander Nguyen
Times of San Diego 

June 8, 2014

The origins and steps of obesity-related diabetes have been established for the first time, according to a significant set of findings just published by researchers at the UCSD School of Medicine.

The researchers concentrated on a protein, called ANT2, that they believe causes diabetes in fat people.

UCSD Skaggs School of Pharmacy & Pharmaceutical Sciences. Courtesy of UCSD News Center

“We’ve pinpointed the steps, the way the whole thing happens,” said Jerrold M. Olefsky, associate dean for Scientific Affairs and Distinguished Professor of Medicine at UCSD.

“The research is in mice, but the evidence suggests that the processes are comparable in humans and these findings are important to not just understanding how diabetes begins, but how better to treat it and prevent it.”

In a study published this weekend in the medical journal Cell, the UCSD researchers described a sequence that begins at the cellular level, as cells react to high-fat diets. These high-fat diets can then result in obesity- induced insulin resistance, and then diabetes.

Olefsky and others have previously shown that obesity is characterized by low-grade inflammation in fat tissue, and that this inflammation can become chronic and result in insulin resistance and diabetes. In their most recent findings, the scientists describe the earliest stages of the process which begin before obesity manifests itself.

The scientists began by feeding mice a high-fat diet. They noticed that the high levels of saturated fatty acids in the diet activated a protein in the fat cell membranes, which in turn caused increased oxygen consumption in the cells.

The increased oxygen consumption by the ANT2 protein left less oxygen for the rest of the cell.

Without an adequate oxygen supply, the cells go through a process that ultimately launches the immune system’s inflammatory response system. A sustained high-fat diet ensured that the process continued unimpeded, and that led to obesity, chronic tissue inflammation and insulin resistance in the mice.

The researches found that by controlling certain aspects of the process, they could protect the mice from inflammation, insulin resistance and elevated glucose levels that were caused by the high-fat diet.

The researches suggest that by impeding two specific steps in the sequence, they could blunt or even reverse the damaging cellular sequence.

— City News Service

It seems that four times a week may be the ideal workout schedule

There were, remarkably, almost no differences in fitness gains among the groups. The women working out twice a week had become as powerful and aerobically fit as those who had worked out six times a week. There were no discernible differences in cytokine levels among the groups, either.

However, the women exercising four times per week were now expending far more energy, over all, than the women in either of the other two groups. They were burning about 225 additional calories each day, beyond what they expended while exercising, compared to their calorie burning at the start of the experiment.

The twice-a-week exercisers also were using more energy each day than they had been at first, burning almost 100 calories more daily, in addition to the calories used during workouts.

But the women who had been assigned to exercise six times per week were now expending considerably less daily energy than they had been at the experiment’s start, the equivalent of almost 200 fewer calories each day, even though they were exercising so assiduously.

“We think that the women in the twice-a-week and four-times-a-week groups felt more energized and physically capable” after several months of training than they had at the start of the study, says Gary Hunter, a U.A.B. professor who led the experiment. Based on conversations with the women, he says he thinks they began opting for stairs over escalators and walking for pleasure.

The women working out six times a week, though, reacted very differently. “They complained to us that working out six times a week took too much time,” Dr. Hunter says. They did not report feeling fatigued or physically droopy. Their bodies were not producing excessive levels of cytokines, sending invisible messages to the body to slow down.

Rather, they felt pressed for time and reacted, it seems, by making choices like driving instead of walking and impatiently avoiding the stairs.

Why Four Workouts a Week May Be Better Than Six
By GRETCHEN REYNOLDS
New York Times
February 13, 2013

A common concern about exercise is that if you don’t do it almost every day, you won’t achieve much health benefit. But a commendable new study suggests otherwise, showing that a fairly leisurely approach to scheduling workouts may actually be more beneficial than working out almost daily.

For the new study, published this month in Medicine & Science in Sports & Exercise, researchers at the University of Alabama at Birmingham gathered 72 older, sedentary women, ages 60 to 74, and randomly assigned them to one of three exercise groups.

One group began lifting weights once a week and performing an endurance-style workout, like jogging or bike riding, on another day.

Another group lifted weights twice a week and jogged or rode an exercise bike twice a week.

The final group, as you may have guessed, completed three weight-lifting and three endurance sessions, or six weekly workouts.

The exercise, which was supervised by researchers, was easy at first and meant to elicit changes in both muscles and endurance. Over the course of four months, the intensity and duration gradually increased, until the women were jogging moderately for 40 minutes and lifting weights for about the same amount of time.

The researchers were hoping to find out which number of weekly workouts would be, Goldilocks-like, just right for increasing the women’s fitness and overall weekly energy expenditure.

Some previous studies had suggested that working out only once or twice a week produced few gains in fitness, while exercising vigorously almost every day sometimes led people to become less physically active, over all, than those formally exercising less. Researchers theorized that the more grueling workout schedule caused the central nervous system to respond as if people were overdoing things, sending out physiological signals that, in an unconscious internal reaction, prompted them to feel tired or lethargic and stop moving so much.

To determine if either of these possibilities held true among their volunteers, the researchers in the current study tracked the women’s blood levels of cytokines, a substance related to stress that is thought to be one of the signals the nervous system uses to determine if someone is overdoing things physically. They also measured the women’s changing aerobic capacities, muscle strength, body fat, moods and, using sophisticated calorimetry techniques, energy expenditure over the course of each week.

By the end of the four-month experiment, all of the women had gained endurance and strength and shed body fat, although weight loss was not the point of the study. The scientists had not asked the women to change their eating habits.

There were, remarkably, almost no differences in fitness gains among the groups. The women working out twice a week had become as powerful and aerobically fit as those who had worked out six times a week. There were no discernible differences in cytokine levels among the groups, either.

However, the women exercising four times per week were now expending far more energy, over all, than the women in either of the other two groups. They were burning about 225 additional calories each day, beyond what they expended while exercising, compared to their calorie burning at the start of the experiment.

The twice-a-week exercisers also were using more energy each day than they had been at first, burning almost 100 calories more daily, in addition to the calories used during workouts.

But the women who had been assigned to exercise six times per week were now expending considerably less daily energy than they had been at the experiment’s start, the equivalent of almost 200 fewer calories each day, even though they were exercising so assiduously.

“We think that the women in the twice-a-week and four-times-a-week groups felt more energized and physically capable” after several months of training than they had at the start of the study, says Gary Hunter, a U.A.B. professor who led the experiment. Based on conversations with the women, he says he thinks they began opting for stairs over escalators and walking for pleasure.

The women working out six times a week, though, reacted very differently. “They complained to us that working out six times a week took too much time,” Dr. Hunter says. They did not report feeling fatigued or physically droopy. Their bodies were not producing excessive levels of cytokines, sending invisible messages to the body to slow down.

Rather, they felt pressed for time and reacted, it seems, by making choices like driving instead of walking and impatiently avoiding the stairs.

Despite the cautionary note, those who insist on working out six times per week need not feel discouraged. As long as you consciously monitor your activity level, the findings suggest, you won’t necessarily and unconsciously wind up moving less over all.

But the more fundamental finding of this study, Dr. Hunter says, is that “less may be more,” a message that most likely resonates with far more of us. The women exercising four times a week “had the greatest overall increase in energy expenditure,” he says. But those working out only twice a week “weren’t far behind.”

The New Science of Mind: Chromosomes, genes, depression, autism, schizophrenia

The New Science of Mind
New York Times
By ERIC R. KANDEL
Published: September 6, 2013

THESE days it is easy to get irritated with the exaggerated interpretations of brain imaging — for example, that a single fMRI scan can reveal our innermost feelings — and with inflated claims about our understanding of the biological basis of our higher mental processes.

Such irritation has led a number of thoughtful people to declare that we can never achieve a truly sophisticated understanding of the biological foundation of complex mental activity.

In fact, recent newspaper articles have argued that psychiatry is a “semi-science” whose practitioners cannot base their treatment of mental disorders on the same empirical evidence as physicians who treat disorders of the body can. The problem for many people is that we cannot point to the underlying biological bases of most psychiatric disorders. In fact, we are nowhere near understanding them as well as we understand disorders of the liver or the heart.

But this is starting to change.

Consider the biology of depression. We are beginning to discern the outlines of a complex neural circuit that becomes disordered in depressive illnesses. Helen Mayberg, at Emory University, and other scientists used brain-scanning techniques to identify several components of this circuit, two of which are particularly important.

One is Area 25 (the subcallosal cingulate region), which mediates our unconscious and motor responses to emotional stress; the other is the right anterior insula, a region where self-awareness and interpersonal experience come together.

These two regions connect to the hypothalamus, which plays a role in basic functions like sleep, appetite and libido, and to three other important regions of the brain: the amygdala, which evaluates emotional salience; the hippocampus, which is concerned with memory; and the prefrontal cortex, which is the seat of executive function and self-esteem. All of these regions can be disturbed in depressive illnesses.

In a recent study of people with depression, Professor Mayberg gave each person one of two types of treatment: cognitive behavioral therapy, a form of psychotherapy that trains people to view their feelings in more positive terms, or an antidepressant medication. She found that people who started with below-average baseline activity in the right anterior insula responded well to cognitive behavioral therapy, but not to the antidepressant. People with above-average activity responded to the antidepressant, but not to cognitive behavioral therapy. Thus, Professor Mayberg found that she could predict a depressed person’s response to specific treatments from the baseline activity in the right anterior insula.

These results show us four very important things about the biology of mental disorders. First, the neural circuits disturbed by psychiatric disorders are likely to be very complex.

Second, we can identify specific, measurable markers of a mental disorder, and those biomarkers can predict the outcome of two different treatments: psychotherapy and medication.

Third, psychotherapy is a biological treatment, a brain therapy. It produces lasting, detectable physical changes in our brain, much as learning does.

And fourth, the effects of psychotherapy can be studied empirically. Aaron Beck, who pioneered the use of cognitive behavioral therapy, long insisted that psychotherapy has an empirical basis, that it is a science. Other forms of psychotherapy have been slower to move in this direction, in part because a number of psychotherapists believed that human behavior is too difficult to study in scientific terms.

ANY discussion of the biological basis of psychiatric disorders must include genetics. And, indeed, we are beginning to fit new pieces into the puzzle of how genetic mutations influence brain development.

Most mutations produce small differences in our genes, but scientists have recently discovered that some mutations give rise to structural differences in our chromosomes. Such differences are known as copy number variations.

People with copy number variations may be missing a small piece of DNA from a chromosome, or they may have an extra piece of that DNA.

This single segment of chromosome 7 contains about 25 of the 21,000 or so genes in our genome, yet an extra copy or a missing copy has profound, and radically different, effects on social behavior.

The second finding is de novo point mutations, which arise spontaneously in the sperm of adult men. Sperm divide every 15 days. This continuous division and copying of DNA leads to errors, and the rate of error increases significantly with age: a 20-year-old will have an average of 25 de novo point mutations in his sperm, whereas a 40-year-old will have 65. These mutations are one reason older fathers are more likely to have children with autism and schizophrenia...

Eric R. Kandel, a professor at the Mortimer B. Zuckerman Mind Brain Behavior Institute at Columbia, a senior investigator at the Howard Hughes Medical Institute and a recipient of the 2000 Nobel Prize in Physiology or Medicine, is the author of “The Age of Insight: The Quest to Understand the Unconscious in Art, Mind and Brain, From Vienna 1900 to the Present.”

Matthew State, at the University of California, San Francisco, has discovered a remarkable copy number variation involving chromosome 7. An extra copy of a particular segment of this chromosome greatly increases the risk of autism, which is characterized by social isolation. Yet the loss of that same segment results in Williams syndrome, a disorder characterized by intense sociability.