Bear-ly Understanding Diabetes

May 30, 2014

By Medical Discovery News

What can studying grizzly bears reveal about human diabetes?

While they are some of the largest bears on earth, Grizzly bears aren’t usually accused of being fat. Regardless, these animals are helping scientists discover new and better treatments for human obesity and diabetes.

Grizzlies spend the late summers consuming more than 50,000 calories per day. As a comparison, a moderately active 50-year-old human female is recommended 2,300. Grizzlies then hibernate for up to seven months, relying on the pounds of stored fat they accumulated before winter. While hibernating, bears do not eat, urinate, or defecate. 

Scientists wondered if all the weight and fat bears gain results in diabetes like it does in humans. Overweight people face an increased risk of type 2 diabetes, in which the body does not make enough of the hormone insulin or cells do not respond to it. Insulin helps move a type of sugar called glucose from the blood into cells, where it is used for energy and as a precursor for other molecules the body needs. If sugar levels in the blood remain elevated and the body doesn’t have enough insulin, cells are starved for energy, leading to damaged eyes, kidneys, nerves, and hearts. 

Interestingly, Grizzly bears can actually control their insulin responsiveness. When they are the fattest, they are most sensitive to insulin, thereby keeping their blood sugar levels healthy. Soon after going into hibernation, they switch to complete insulin resistance, meaning they develop type 2 diabetes. But unlike humans, their blood sugar levels remain normal. When they awaken in the spring, their insulin responsiveness is restored. Bears do this not so much to regulate their blood sugar levels as to regulate their storage and utilization of fat. So how do bears control their insulin responsiveness? And could it lead to new treatments for type 2 diabetes in humans?

PTEN is a protein that regulates cells’ sensitivity to insulin. Scientists know exactly when Grizzlies increase or decrease PTEN activity, they just don’t know how. People with a PTEN mutation have a metabolism similar to Grizzlies’.  These people have an increased risk of obesity and cancer but a decreased risk of developing type 2 diabetes because they are more sensitive to insulin.

Grizzlies have also evolved to the ability to accumulate large amounts of fat only in their adipose tissue, just below the skin so it doesn’t interfere with the rest of their bodies. In humans, on the other hand, fat can accumulate in many places like the liver, in muscles, and around other internal organs, which are all highly unhealthy places to keep fat. Bears can also have elevated levels of cholesterol without the serious consequences of cardiovascular disease.

During hibernation, the Grizzly bears’ kidneys shut down. But despite the high levels of toxins that accumulate in the blood without working kidneys, they don’t die or even suffer from it like a human would. When they wake up, their kidney function is restored with no permanent damage.

After millions of years of evolution, Grizzly bears and other animals have developed solutions for biological challenges humans still face. Studying them is a new approach that has the potential to create treatments for many human conditions.

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What Makes a Male?

May 16, 2014

By Medical Discovery News

What makes a male?

Despite centuries of women being celebrated for siring sons, or scorned for failing to produce an heir, it is actually men who determine a baby’s gender. Women give each of their offspring an X chromosome, but the male can give an X or a Y chromosome to create a female (XX) or male (XY), respectively. But how much of the Y chromosome is required to make a male? It turns out only two genes are needed to create a male mouse, a species that determines gender the same as humans. 

Humans have 23 pairs of chromosomes, one of which is the sex chromosome. Chromosomes contain lots and lots of genes, all which carry instructions that tell different parts of the body what to do. In males, the Y chromosome carries a gene called SRY that encodes the Sex-determining region Y (also abbreviated SRY) protein. This protein, as its name suggests, will decide the sex of future offspring. Consequently, this one single gene, SRY, is all that’s required to produce an anatomically male mouse. However, these male mice are infertile because they lack some of the genes involved in sperm production.

That’s where another gene called Eif2s3y comes in. With this second gene, male mice can at least generate sperm cell precursors known as round spermatids, but not mature sperm. To fully develop sperm, the mice need both copies of this gene. One is toward the end of the Y chromosome and the other version is on the X chromosome.

So with only two genes from the Y chromosome, male mice are able to produce immature sperm. Scientists used an assisted in vitro fertilization technique to treat male infertility by injecting the round spermatids directly into the eggs of female mice. The round spermatids fertilized the eggs nine percent of the time. In comparison, sperm from natural-born male mice fertilized eggs 26 percent of the time. The offspring born from these efforts developed into normal, healthy, fertile adult mice. 

Even though only two genes from the Y chromosome are required to produce fertile adult mice, the Y chromosome is still important. More genes are required to produce fully mature, motile sperm capable of fertilizing an egg without intervention. The Eif2s3y gene may play a role in some forms of male infertility in humans. With this new data, therapies could be invented to encourage the development of functional sperm that could reproduce through in vitro methods. Injecting round spermatid into eggs is not currently an option for humans due to technical and safety issues, but this technique is likely to get better with additional research. 

The genetic information contained in the Y chromosome plays important roles in reproduction by controlling the development of sperm and normal fertilization and will continue to do so, negating suggestions that it is being eliminated by evolution or rendered useless by in vitro fertilization. For now at least, men remain indispensable.