Nature

This blind fish is giving scientists a new perspective on diabetes


The pale, eyeless pink Mexican cavefish is surprisingly chubby for a fish that lives in an environment with a big lack of algae food.

Now a team of researchers have figured out how this can be, and it’s identical to a mechanism that causes insulin resistance in humans.

 

Insulin is a hormone produced by the pancreas to help regulate the amount of glucose in your blood. When you eat, your body converts carbohydrates into glucose, which your body can use as fuel.

The insulin binds to its receptor on the surface of muscle, fat and liver cells, which triggers them to take up glucose from the blood. This returns blood sugar levels to normal, and fuels your body, using some of the glucose for energy and storing the excess for later in the form of glycogen.

If you don’t eat for a while, and your blood sugar levels drop, the pancreas releases a second hormone, glucagon. This does the opposite, telling the liver and muscles to convert glycogen back into glucose and release it back into the bloodstream, thus restoring normal blood sugar levels.

This process of maintaining equilibrium is known as homeostasis.

There are different forms of diabetes, but they all prevent insulin from doing its job properly, resulting in an excess of glucose in the bloodstream. It’s dangerous in humans, but it looks like one species’ serious disorder is another’s survival loophole.

Mexican tetra fish (Astyanax mexicanus) consist of two distinct populations. There are the silver-grey river-dwelling populations, with access to sunlit waters (and eyes); and the plump pink cave-dwelling populations, which, down in the dark under the surface of the Earth, experience long periods of food deprivation.

(Riddle et al./Nature)

It had previously been observed that, when starved, the cavefish lose much less weight compared to their river-dwelling conspecifics. There are several factors that contribute to this, including reduced metabolic circadian rhythm, decreased metabolic rate and elevated body fat, but the genetic changes underneath these had remained a mystery.

Under Nicolas Rohner of the Stowers Institute for Medical Research in the US and led by biologist Misty Riddle, a team of researchers has now determined that the cavefish have developed a mutated version of the insulin receptor, so that insulin does not bind.

 

They raised both river and cave populations of Astyanax Mexicanus in a lab, and monitored their blood glucose. They found that the cavefish had higher blood glucose levels than riverfish both after feeding and short-term fasting.

However, after long-term fasting – 21 days – the cavefish had a much bigger drop in blood glucose than riverfish. This suggests that poorly regulated blood glucose homeostasis is characteristic of cavefish populations.

To investigate the underlying genetic mechanism, the researchers examined the sequences of all known genes in the insulin pathway, using previously sequenced genome data. It was there that they found a coding difference in the insulin receptor gene between riverfish and cavefish, correlating with insulin resistance.

This mutation sees the amino acid residue proline replaced with leucine. This genetic alteration has been implicated in at least two known cases of a rare disorder called Rabson-Mendenhall Syndrome, which is characterised by severe insulin resistance.

In spite of hyperglycaemia and a fatty liver, both of which are associated with Type 2 diabetes, by age 14 the cavefish show less signs of ageing compared to their surface dwelling cousins. There is also no difference in fertility decline, indicating that the evolutionary “cost” of starvation resistance to physiological health is minor.

 

This means they may also have evolved compensatory mechanisms to stay healthy, despite a mutation that causes deleterious health effects in humans, the researchers said. These potential mechanisms are definitely worth further investigation.

“Our findings establish cavefish as a model with which to investigate resistance to pathologies of diabetes-like dysregulation of glucose homeostasis,” the researchers wrote in their paper.

“Moreover, our results highlight the extreme physiological measures that can evolve in critical metabolic pathways to accommodate exceptional environmental challenges.”

The paper has been published online in the journal Nature, with an accompanying editorial.

 



Source link

Products You May Like

Articles You May Like

Fire erupting from cracks in the ground, Andhra Pradesh, India
Former Iran president quotes Tupac Shakur: Mahmoud Ahmadinejad attacks USA with Changes | Weird | News
trail of destruction, dozens dead and missing, farming sector worst affected
ALIENS created Hurricane Michael and left evidence – shock claim | Weird | News
In video: Road destroyed by strange geological event in Oman

Leave a Reply

Your email address will not be published. Required fields are marked *