- Messages
- 8,470
- Type of diabetes
- Type 2
- Treatment type
- Tablets (oral)
De-Differentiation became a buzzword last year, and it entered and nearly derailed a few threads here in the Forum, so I feel it deserves its own topic thread. I have placed it in the Soapbox section because discussion on this topic can become quite heated, The purpose of this thread is to discuss and learn about the subject, not win points.
When i was diagnosed some 30 years ago as a nascent T2D (Newbie) I was informed by the experts at that time that the condition is progressive, and will lead to needing insulin treatment within 10 years at most. i was informed that my beta cells will suffer apoptosis and fail. The cause of T2D in those days was believed to be insulin resistance in the muscle tissue, which could only be overcome by massive excess of insulin in the manner of a sledgehammer cracking a nut. I have learnt since that this is only part of the story, and that management of the condition has improved.
We do know that beta cell output does deplete with T2D, and that beta cell mass does change as the condition progresses, but recent experiments have demonstrated that for some T2D it is possible to recover beta cell output to the point of not requiring diabtic medications. So beta cells do not always die, some just go off the radar but can be recovered apparently through the intervention via a diet that mimics bariatric surgery outcomes. At present only one diet has been recognised as being suitable, and that is the very low calorie diet(VLC). However the study that proved this used a diet that was not only calorie restricted, but was also a low carb diet at the same time. So there are IMHO potentially 2 diets that may have this effect
The old theory of beta cell death through exhaustion does not exlain how beta cells that stopped output can suddenly recover almost full output just through losing some weight. This is where de-differentiation raises its head, as a theory (so far) that can explain what the beta cells do when they are not on duty.
Let me start by looking at what differentiation means in terms of the beta cell (in all cell actually). It is a term used by endocrinologists (called endo's henceforth) that describe the process that occurs shortly after conception whereby nascent stem cells get programmed by the DNA to perform their different tasks, i,e the RNA formula that they use to control their activities.
There is no evidence found so far that any cell in our body gets reprogrmmed to perform a different function or revert back to being a stem cell. Yes, some cells do change, but this is what we call cancer. Damaged cells such as happens all the time from toxin, radiation, virus etc are detected by our immune system and are removed naturally as they occur. So cancer cells are damaged cells that have an altered DNA, but which are not detected as alien to our body. Cancer cells seem to serve no function except replicate and grow,
Beta cells do not get replaced unlike most of the other cells in our body. The pancreas starts its work from the get-go with a full set of beta cells within the first month following conception.
So what is de-differentiation? There are currently two definitions. The original definition as used by the endo' is that sometimes cell lose some or all of their programming info (their RNA code) and stop providing their original function. They remain identified as being part of our body so do not get removed by the immune system, and they do not replicate like cancer. It is akin to the Microsoft BSOD condition, where something significant needs to be done to reboot them back into useful function. Until that happens, they could be described as being dormant. A recent study has shown that the pancreas does contain dormant beta cells, and that under certain (surgical) conditions, they can become active again. this is a by product of pancreatic surgery.
But Prof Roy Taylor has taken this a step further in relation to beta cells. He is currently seeking funding for research to investigate his theory which in essence is that instead of becoming dormant, the de-differentiation of the beta cell is such that it takes on the function of an Alpha cell instead (i.e. is reprogrammed as an Alpha) and starts producing glucagon instead of insulin. For it to do this it would have to be damaged in such a way as to replace the RNA code for insulin by that for glucagon. Thus it requires our bodies to engineer a gene splicing within the cell when it gets distressed by T2D. Not too sure if this is possible, and I am unaware of any other cell in the body changing its function like this.
What is even more astounding is the claim by Roy in his application paper that the VLC diet that leads to 15% weight loss also induces the same process, but in reverse to turn the cell back into a Beta. In my mind this is not logical, so it will be interesting to see what his research finds.
https://pubmed.ncbi.nlm.nih.gov/27926891/
In my laymans mind, I see a simpler explanation that does not need de-differentiation at all.
If weight loss improves the beta cell function (not yet proven since all tests in vivo so far are on the panceras output not individual cell outputs) then if weight in the form of ectopic fat within the pancreas can repair the damage when it is removed, then probably the same weight gain in the pancreas organ is causing a problem. Now maybe the fat is blocking a pathway for the enzyme demand signal, or is stopping calcium getting into the cell (required to give the switch on voltage that starts insulin production), or is simply blocking the output portal of the beta cell so insulin is not stored or released then these are mechanisms that make sense. I would personally plump for the calcium being interferred with but a blocked drain also does it for me.
When i was diagnosed some 30 years ago as a nascent T2D (Newbie) I was informed by the experts at that time that the condition is progressive, and will lead to needing insulin treatment within 10 years at most. i was informed that my beta cells will suffer apoptosis and fail. The cause of T2D in those days was believed to be insulin resistance in the muscle tissue, which could only be overcome by massive excess of insulin in the manner of a sledgehammer cracking a nut. I have learnt since that this is only part of the story, and that management of the condition has improved.
We do know that beta cell output does deplete with T2D, and that beta cell mass does change as the condition progresses, but recent experiments have demonstrated that for some T2D it is possible to recover beta cell output to the point of not requiring diabtic medications. So beta cells do not always die, some just go off the radar but can be recovered apparently through the intervention via a diet that mimics bariatric surgery outcomes. At present only one diet has been recognised as being suitable, and that is the very low calorie diet(VLC). However the study that proved this used a diet that was not only calorie restricted, but was also a low carb diet at the same time. So there are IMHO potentially 2 diets that may have this effect
The old theory of beta cell death through exhaustion does not exlain how beta cells that stopped output can suddenly recover almost full output just through losing some weight. This is where de-differentiation raises its head, as a theory (so far) that can explain what the beta cells do when they are not on duty.
Let me start by looking at what differentiation means in terms of the beta cell (in all cell actually). It is a term used by endocrinologists (called endo's henceforth) that describe the process that occurs shortly after conception whereby nascent stem cells get programmed by the DNA to perform their different tasks, i,e the RNA formula that they use to control their activities.
There is no evidence found so far that any cell in our body gets reprogrmmed to perform a different function or revert back to being a stem cell. Yes, some cells do change, but this is what we call cancer. Damaged cells such as happens all the time from toxin, radiation, virus etc are detected by our immune system and are removed naturally as they occur. So cancer cells are damaged cells that have an altered DNA, but which are not detected as alien to our body. Cancer cells seem to serve no function except replicate and grow,
Beta cells do not get replaced unlike most of the other cells in our body. The pancreas starts its work from the get-go with a full set of beta cells within the first month following conception.
So what is de-differentiation? There are currently two definitions. The original definition as used by the endo' is that sometimes cell lose some or all of their programming info (their RNA code) and stop providing their original function. They remain identified as being part of our body so do not get removed by the immune system, and they do not replicate like cancer. It is akin to the Microsoft BSOD condition, where something significant needs to be done to reboot them back into useful function. Until that happens, they could be described as being dormant. A recent study has shown that the pancreas does contain dormant beta cells, and that under certain (surgical) conditions, they can become active again. this is a by product of pancreatic surgery.
But Prof Roy Taylor has taken this a step further in relation to beta cells. He is currently seeking funding for research to investigate his theory which in essence is that instead of becoming dormant, the de-differentiation of the beta cell is such that it takes on the function of an Alpha cell instead (i.e. is reprogrammed as an Alpha) and starts producing glucagon instead of insulin. For it to do this it would have to be damaged in such a way as to replace the RNA code for insulin by that for glucagon. Thus it requires our bodies to engineer a gene splicing within the cell when it gets distressed by T2D. Not too sure if this is possible, and I am unaware of any other cell in the body changing its function like this.
What is even more astounding is the claim by Roy in his application paper that the VLC diet that leads to 15% weight loss also induces the same process, but in reverse to turn the cell back into a Beta. In my mind this is not logical, so it will be interesting to see what his research finds.
https://pubmed.ncbi.nlm.nih.gov/27926891/
In my laymans mind, I see a simpler explanation that does not need de-differentiation at all.
If weight loss improves the beta cell function (not yet proven since all tests in vivo so far are on the panceras output not individual cell outputs) then if weight in the form of ectopic fat within the pancreas can repair the damage when it is removed, then probably the same weight gain in the pancreas organ is causing a problem. Now maybe the fat is blocking a pathway for the enzyme demand signal, or is stopping calcium getting into the cell (required to give the switch on voltage that starts insulin production), or is simply blocking the output portal of the beta cell so insulin is not stored or released then these are mechanisms that make sense. I would personally plump for the calcium being interferred with but a blocked drain also does it for me.
Last edited: