Autophagy & Type-2 Diabetes: Should We 'Treat' at All?

[mktsgm]

With this year's Nobel prize for physiology going to autophagy related research, the interest in autophagy and its roles in health and disease is rekindled.

Autophagy is an important cellular process which clears the cell debris and promotes health. So the autophagy process should never be interfered with for good health.

It is surmised that Type-2 diabetes is a condition where autophagy is an on-going process or interrupted process. If the process of autophagy of pancreatic beta/alpha cells is completed on its own, the disease would resolve on its own.

It is well known that Glucagon is a major inducer of autophagy in liver. Glucagon promotes glycolysis, causing an increase in blood plasma glucose. It suppresses insulin. Exactly the same conditions we experience in Type-2 diabetes.

Then the raised glucose/glucagon levels and suppressed insulin levels are quite normal and expected. If so, why should we see diabetes as an abnormal condition? Once the autophagy mechanism which is currently active and when the removal of cell debris work is over, things should fall into their place.

My question is why don't we consider Type-2 Diabetes as a transient condition and glucose would come down to normal levels once the autophagy mechanism has finished its job. Should we 'treat' diabetes at all?

 

[BillTre]

My question is why don't we consider Type-2 Diabetes as a transient condition and glucose would come down to normal levels once the autophagy mechanism has finished its job. Should we 'treat' diabetes at all?

Do people die from Type-2 Diabetes or have their lives significantly affected? Maybe not just a transient condition.
If so, good reason to treat.

 

[Ygggdrasil]

It is surmised that Type-2 diabetes is a condition where autophagy is an on-going process or interrupted process. If the process of autophagy of pancreatic beta/alpha cells is completed on its own, the disease would resolve on its own.

I'm not too familiar with this field. Do you have some references that discuss these two statements in more detail? I thought that Type-2 diabetes had to do with normal cell's inability to respond to insulin, not any dysfunction of the pancreatic alpha and beta cells.

 

[jim mcnamara]

Hmm. https://www.ncbi.nlm.nih.gov/pubmed/21029295
Sort of a review of that question, discusses β-cell pathology and autophagy

 

[mktsgm]

Thanks. I saw the article. There area many such articles which emphasise role of autophagy in diabetes. I wonder why the medical world has largely ignored this connection.

In diabetes our target seems to be hyperglycemia, not the root cause.

 

[Ygggdrasil]

From the abstract of the review cited by @jim mcnamara

In this review we attempt to give an overview of the data generated by others and by us in view of the possible role of autophagy in diabetes, a role which depending on the conditions, could be beneficial or detrimental in coping with stress.

(emphasis mine)

At least that review does not give the impression that the role of autophagy in diabetes is well understood (or if it is even clear whether altered autophagy is causal of the disease).

 

[jim mcnamara]

I believe type II is currently thought to be as @Ygggdrasil describes - environmental - i.e., caloric overload, usually from carbohydrates. I have personally seen it in action in an isolated population on a US Indian reservation after the introduction of USDA food stamps. In 1980, on the Navajo Reservation there were no reported cases of Type II in anyone under the age of 18. Prior to the introduction of food stamps in 1968, type II was seldom reported in any patient. Obesity was less than 10%. It is now prevalent among clinically obese children between ages 12 - 18. This is from conversations with IHS staff over the past 40 years.

So, I would suggest that massive calorie overload has to happen. Humans did not evolve in a world where Coca-cola and Pringles chips were standard fare for dinner.

PS: Navajos have had perennial problems with potable water, and the tradition has been to buy multiple cases of Coca-cola every shopping trip, since it is paid for by the food stamp program.

http://www.fns.usda.gov/snap/eligible-food-items

So someone doesn't ask and turn the thread upside down: Why can people buy junk food with food stamps?
http://asktheexpert.custhelp.com/app/answers/detail/a_id/5268/related/1

The real reason is political pressure from US agribusiness marketers - Coca-cola contains substantial sugar produced in the US - either as cane sugar or high fructose corn syrup. The drink is: simple sugar (fructose and or sucrose), carbonated filtered water, caramel coloring, citric acid, and a 'secret' flavoring. Plus some other goodies. See:
https://en.wikipedia.org/wiki/Coca-Cola_formula

Coca-cola is a proxy for lots of different sugar drinks available, BTW. I use that because it is a preferred drink.
https://ndb.nal.usda.gov/ndb/foods/show/92190?manu=&fgcd=&ds=Branded Food Products

Bottom line:
So, if you require 2 liters of liquid daily, then you are skewing the traditional diet by 265g of simple sugar, ~1050 kCal. A 2000 kCal diet with water becomes a 3050 Kcal diet. Which represents a net weight gain of 2 lbs (.89 Kg) body weight per week, all other things held constant. This is a 30% caloric overload, over years, which did not occur historically, specifically did not occur prior to food stamps being used on the Reservation.

Remote populations are good for modeling nutritional effects. Modeled this issue in an IHS white paper in the 1970's. Another later update in 1982, I think. I cannot find either one.