Testosterone Chases Viagra in Libido Race as Doctors Fret

Prescriptions for testosterone replacement therapies have more than doubled since 2006 to 5.6 million, according to data compiled by Bloomberg. Peter Snyder, MD, professor of Endocrinology, requires his male patients take multiple blood tests in the morning to ensure their testosterone levels are below the normal range of 300 to 1,200 nanograms per deciliter.

“It’s likely the dramatic increase in use of testosterone is mostly for people whose blood test is a little bit low, but for no obvious reason other than age,” Snyder said. “It really isn’t clear that those people are going to benefit.” Snyder, who is studying the effects of testosterone in older men, said the increased popularity signals an overuse of the drugs. He said he won’t prescribe testosterone unless a patient has significantly low testosterone and symptoms, like depression, low sex drive or fatigue.

>> Bloomberg Article

A Penn research team, led by Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine, University of Pennsylvania, reports in Nature Medicine that mice in which an enzyme called histone deacetylase 3 (HDAC3) was deleted had massively fatty livers, but lower blood sugar, and were thus protected from glucose intolerance and insulin resistance, the hallmark of diabetes.

Insulin resistance occurs when the body does a poor job of lowering blood sugars. Typically, patients with obesity and type 2 diabetes have fatty livers, and the dogma in the field, says Lazar, is that the fatty livers contribute to the insulin resistance and diabetes in a vicious cycle. These findings are "a clear counterexample to this thinking," he says.

The researchers observed that the extra fat in the liver did not cause insulin resistance because it was sequestered in tiny lipid droplets inside individual liver cells, coated by a specific protein. The metabolites that would otherwise be used by the body to make glucose were re-routed to make fat, leading to reduced glucose in the bloodstream. The advantage of the lower blood sugar is tempered by the excess liver fat, which can lead to problems of its own, including liver failure.

>> Read Press Release

May 1, 2012

Best Paper:
Dr. Lazar

Authored by Dr. Mitchell Lazar, the paper, "Diet-induced Lethality Due to Deletion of the Hdac3 Gene in Heart and Skeletal Muscle," has been designated as one of the best papers published by the Journal of Biological Chemistry in 2011. The journal's editors selected only 20 papers—out of the more than 4,000 that were published last year—to receive this special designation. One paper was chosen for each of their affinity groups, and this paper represents the Metabolism affinity group. Dr. Lazar is the Sylvan Eisman Professor of Medicine and director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine.

>> View Almanac

May 1, 2012

Arthur H. Rubenstein, MBBCh Former Perelman School of Medicine Dean, Receives Prestigous Medal for Medical Service

Arthur H. Rubenstein, MBBCh, was awarded the highest honor of the Association of American Physicians (AAP), the George M. Kober Medal, this week at the annual joint meeting of the AAP and the American Society for Clinical Investigation.

Since 1925, the association has bestowed the award for research in scientific medicine that rises to the highest level of achievement. Rubenstein and mentor Donald Steiner developed the first accurate way to measure insulin secretion in diabetic patients being treated with insulin derived from the pancreas of cattle or pigs. This method was key to the commercial production of human insulin for diabetics. Rubenstein and Steiner were also part of a team that discovered the first case of diabetes caused by abnormal insulin.

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Circadian Rhythms: The Timekeepers Within

Circadian rhythms have a direct impact on human health, and understanding about how the internal timekeepers in the brain and other organs communicate and what happens to put them out of sync is important. The most recent discoveries involve so-called clock genes, first identified in 1994. The liver, for example, relies on its clock genes to predict when food will be consumed so its cells will be revved up to metabolize and store nutrients.

“If people eat when the liver isn’t anticipating nutrients coming into the body, it can’t regulate sugar and fat metabolism properly,” says Mitchell A. Lazar, director of the Institute for Diabetes, Obesity, and Metabolism, in Proto magazine. “That dissonance can lead to extra fat in the liver and contribute to diabetes and lipid disorders.”

>> Proto Magazine Article

April 8, 2012

Study finds gene variants behind childhood obesity risk

Scientists have discovered two gene variants that appear to play a critical role in the development of common childhood obesity, according to a large genetic study released Sunday. The discovery could eventually lead to treatments and specific lifestyle advice for heavy children.Scientists have discovered two gene variants that appear to play a critical role in the development of common childhood obesity, according to a large genetic study released Sunday. The discovery could eventually lead to treatments and specific lifestyle advice for heavy children.

This research "robustly" shows that these two gene variants predispose some children to obesity more than others, said Struan Grant, associate director of the Center for Applied Genomics at The Children's Hospital of Philadelphia. "Childhood obesity is partly in your genes. It's partly your lifestyle."

April 4, 2012

Penn Medicine Researchers Find that Molecular Pair Controls Time-Keeping a Metabolism

The 24-hour internal clock controls many aspects of human behavior and physiology, including sleep, blood pressure, and metabolism. Disruption in circadian rhythms leads to increased incidence of many diseases, including metabolic disease and cancer. Each cell of the body has its own internal timing mechanism, which is controlled by proteins that keep one another in check.

One of these proteins, called Rev-erb alpha, was thought to have a subordinate role because the clock runs fairly normally in its absence. New work, published in Genes and Development this month, from the lab of Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine, University of Pennsylvania, found that a closely related protein called Rev-erb beta serves as a back-up for Rev-erb alpha. When both are not functioning, the cellular clock loses its time-keeping function.

>> Read Press Release

Duality of Longevity Drug Explained by Perelman School of Medicine Researchers
Rapamycin-induced longevity in mice can be uncoupled from diabetes-inducing side effects

A Penn- and MIT-led team explained how rapamycin, a drug that extends mouse lifespan, also causes insulin resistance. The researchers showed in an animal model that they could separate the effects, which depend on inhibiting two protein complexes, mTORC1 and mTORC2, respectively. The study suggests that molecules that specifically inhibit mTORC1 may combat age-related diseases without the insulin-resistance side effect, which can predispose people to diabetes.

Senior author Joseph A. Baur, PhD, assistant professor of Physiology, comments: “The hope is that we're getting close to understanding how these things are happening and may be able to design a better molecule in the future. I don't think anyone who's healthy at this point would have much hope of improving their lifespan by taking rapamycin, given what we know of the side effects.”

Their work is described in the San Antonio Express-News, New Scientist, and a Discover magazine blog.

Penn Press Release