Question: What drives the pancreas to produce insulin except blood sugar?


(Cathrine Helle) #1

Is cortisol one of the culprits?

This is what I’ve come to understand about the insulin hypothesis (which hardly is an hypothesis any longer, but oh well):

  1. Cells become insulin resistant
  2. Pancreas tries to compensate by producing more insulin to keep bloodsugar levels healthy
  3. High insulin levels means fat storing mode
  4. Low insulin levels allow fat burning mode
  5. High insulin levels causes overweight / obesity
  6. High insulin levels AND insulin resistance eventually lead to diabetes type two, because the insulin no longer can keep blood sugars low

In my head this means that you should somehow be able to gauge how insulin resistant people are simply by weight, but this isn’t the case, is it. Skinny people can be type two diabetic and fat people can be insulin sensitive (according to Ivor Cummings).

So I’m curious to know what other mechanisms drive obesity. Obviously there is high insulin and no access to fat stores - but why? If cells are insulin sensitive, blood sugars should be well managed and insulin low. What am I missing?

I’ll include the link to Ivor Cummings talk, it’s long, but very good - perhaps I missed some vital information in there :confused:

Edit: the slides I’m referring to appears around the 35 min mark


(eschor) #2

‘A New Paradigm of Insulin Resistance’ from Low Carb Breck https://t.co/VpJLsJTTox via @YouTube

Dr. Jason Fung - ‘A New Paradigm of Insulin Resistance’
Dr. Jason Fung completed medical school and internal medicine at the University of Toronto before finishing his nephrology fellowship at the University of Ca…
YOUTU.BE/EUISCEBGXXK

this may apply as well…answered questions…or clarified answers for me


(Cathrine Helle) #3

Thank you, I agree, it’s a very good talk. However, it does not shed more light on my initial question which arose after seeing the talk from Ivor Cummings.

Between 35 and 38 minutes in he shows a graphic dividing the population into thirds.

  1. Low/no risk of heart disease/diabetes - no insulin resistance
  2. Medium risk of heart disease/diabetes - insulin resistant
  3. High risk of heart disease - diagnosed T2D

He further states that body fat is not a good measurement to determine if someone is insulin resistant/diabetic/at risk of heart disease, because there are both skinny and obese people in all three categories. He continues on with explaining the mechanisms causing insulin resistance. However he does not go in more depth as to how insulin sensitive people get obese, and that is what I can’t seem to find an answer to :confused:


(Cathrine Helle) #4

I have posted my question in the comment section below the video - hopefully he sees it and have time to answer it :slight_smile:

Anyway - could this be a topic for the podcast? @Carl_Franklin and @richard?

I found your episode on skinny diabetics fascinating and it would be nice to shed some light on fat non diabetics as well :slight_smile:


(Todd Allen) #5

I don’t know the whole story but here are some elements I’ve read about that might partially answer your questions.

Insulin drives nutrient uptake by cells. So it affects a wide range of tissues and it affects nutrients other than glucose, for example it can stimulate cells to take in amino acids. It also is a signaling hormone to other endocrine functions that need to act when there is an abundance of nutrients and I think it has an impact on most if not all endocrine glands.

When insulin is chronically elevated the various tissues it acts upon become less responsive to the signal. How that happens can vary dramatically from person to person. I have a genetic muscle wasting disease that plays havoc on the mitochondria of skeletal muscle. The muscle has diminished ability to absorb and burn glucose so other tissues have to shoulder more of the burden of glucose disposal and to get them to do it the pancreas has to produce more insulin resulting in cascading insensitivity to glucose uptake by multiple tissues.

Other big sinks for glucose are the liver and adipose tissues and these also vary person to person. For example some people are much better than others at growing new subcutaneous fat cells. These people gain weight more easily but tend to be healthier because subcutaneous fat is a great place to store excess energy. And they tend to stay insulin sensitive because it doesn’t take much insulin to get new fat cells to absorb excess nutrients. People with an impaired ability to grow subcutaneous fat cells develop the TOFI syndrome, thin on the outside but fat on the inside with excess energy storing as fat in various organs and tissues elsewhere. When liver fills with fat it becomes insulin resistant which leads to numerous problems. Other organs and tissues such as the heart, muscles and bones can also get choked with fat.

So there are many different flavors of insulin insensitivity and you can have healthy obese people who are exquisitely insulin sensitive where moderate amounts of insulin make their fat soak up too much energy leaving them hungry all the time as their brains demand to be fed.


(A ham loving ham! - VA6KD) #6

Do you think the keto mantra KCKO holds true for these kind of folks if it wasn’t insulin insensitivity that caused the weight gain? I’m starting to wonder if that’s my deal… Relatively metabolically healthy (according to my doc compared to others at my BMI). Relatively low visceral fat (from CT and Dexa scans). I’ve lost weight on keto, but no where near as fast as most seem to report and have now leveled out to <1lb/week with some good stalls too. Don’t get me wrong :slight_smile: I’m 100% committed to KCKO.


(Cathrine Helle) #7

Yes! This addresses my question exactly! So your saying that there might be such a thing as insulin over sensitive? It’s the reversed issue somehow. I wonder how a ketogenic woe plays in to this - I would imagine it to be highly beneficial as insulin is lowered allowing body fat to be metabolised. If there is such a thing as oversensitivity it would make perfect sense that too much glucose would be converted to fat with the inevitable weight gain as a result.

Thank you! :raised_hands:


(Cathrine Helle) #8

This is the paragraph I think explains it so well. Again; thank you :blush:


(Todd Allen) #9

Regardless of whether one is insulin sensitive or not insulin drives energy storage and impedes release of stored fat. A keto diet lowers insulin making it easier to lose weight.

People like myself who don’t easily grow new fat cells and had elevated insulin for a long time eventually get fat and the fat cells are very big and sick and desperate to release their excess fat like over pressured balloons about to pop. Lower the insulin and fat rushes out and we feel energetic and the fat tissue gets healthy, stops the inflammatory signaling and we experience dramatic change at least for a while as the over pressure releases. And then we may struggle when it changes from easy and we still have more healthy/stubborn fat then we want.

Change may come slower for people who generated lots of healthy new fat cells. They need to squeeze out diminishing fat from many cells and kill off and recycle the excess cells. It takes stronger signalling (more time with insulin very low) for that to happen… The body has no urgency to lose healthy fat and it can take longer to get the process started.


(Todd Allen) #10

Yes, KCKO. One thing I failed to mention in my reply to Camomilla is those with healthy fat have the advantage of time. They aren’t likely to suffer a stroke or heart attack before shedding the pounds and probably have suffered less damage to contend with in later years.


(Cathrine Helle) #11

Wow, this is me!!! My weight loss have always been very slow. And I felt really bad for eight weeks starting keto in 2010. I have never had any rush of energy either. But keto proved very useful to me, it’s actually the only way of eating that have let me shed some kilos at all. I would assume that eating a regular diet would drive insulin up that moves too much of the energy to my nice, new subcutaneous freezer :stuck_out_tongue: Leaving my glycogen fridge empty and me hungry :confused:


(A ham loving ham! - VA6KD) #12

Yep. Same here. Keto is the first way of eating that I’ve tried in over 25 years (and I’ve tried A LOT) that leaves me satiated, feeling alive, clear minded, all whilst (slowly) losing weight and not being consumed with watching calories.


(Dory) #13

You mention that fat loss shrinks the adipose cells, which eventually are killed off and recycled. Dr. Ted Naiman stated in episode 29 that when fat cells empty out, they send signals of distress, wanting to be filled back up, and this is interpreted as hunger. If this truly happens, at what point do they give up crying for more fat and go ahead and die? And what can be done (besides fasting and a ketogenic diet) to encourage the recycling of excessive adipose cells? Does their death really then result in reduced appetite?


(Cathrine Helle) #14

That is a good question, that I don’t know the answer to. After my weight loss I had a dramatic increase in appetite. Coupled with paleo (more carbes) I experienced every symptom of a reduced basal metabolic rate. It took almost five years to put the weight back on, but I was not able to turn it around until I went strict keto again. I have been low carb all along, but this doesn’t seem to be enough at all.

I believe that keto and fasting are powerful tools to take control of my metabolic health, and that autophagy might be a way I can force my body to feed on cells that are redundant.


(Cathrine Helle) #15

@brownfat Could you point me in the direction of articles / talks on this topic? I’ve found very little on my own.


(Richard Morris) #16

I think he was saying that a fat cells job is to store energy, when it is full it stops signalling that it can store more. His theory about stalls is that in someone who has had their cells chronically stuffed, that when those fat cells eventually become less stuffed … that signal “I can take some more” is mistaken for “I need some more”.

I don’t agree with Ted.

I suspect the cause of the stall that many people see after losing a lot of weight is their adipose tissue is becoming healthy and willing to store energy, but their fasted insulin is high enough even when they don’t eat carbs to prevent them losing weight.

Someone who is type 2 diabetic has fat cells that are no longer willing to abide by the signal of insulin to hold onto energy. So fat cells are overflowing energy into their circulation. Their pancreases are producing more and more insulin to try to get circulating lipids down. It is one of insulin’s roles to switch us between using fat for energy and using glucose for energy. When glucose is present insulin goes up to turn off the spigot releasing fat into circulation. It also shuts off getting long chained fats into the furnaces to be burned. The idea is when you have glucose in circulation you burn that, and when it drops so does insulin and then your body fat releases energy and your cells burn it.

So the derangement is fat cells unable to live up to that contract any more and releasing free fatty acids into your blood, and cells unable to oxidize that fat.

What happens when we go keto is we lower insulin sufficient to allow our cells to burn fat, and we start drawing down fat in circulation and eventually our body fat becomes willing to listen to insulin again to regulate when they release and store energy,

The point that the stall happens is I believe when your adipose becomes healthy and meets your own level of fasted insulin secretion.


(Cathrine Helle) #17

Thank you for your input, much appreciated! If the above is the case, it still doesn’t explain why it is so hard for people with healthy fat to lose weight.

I’m wondering how bariatric surgery ties in to this as well. According to dr Fung is bariatric surgery basically a forced fast, with all the benefits of fasting but without the envasive surgery. Is there a difference in the obese that are undergoing surgery depending on how insulin resistant they are?


(Cathrine Helle) #18

I’m sorry for being so bothersome asking all these questions. But I don’t understand this and it’s sort of driving me nuts :stuck_out_tongue_winking_eye:


(Todd Allen) #19

Dory, you ask some great questions and I wish I knew the answers.

Tissues including adipose (fat) expand via hypertrophy (cells get bigger) and hyperplasia (more cells). There has been a lot of research showing that for adipose tissue hypertrophy leads to insulin resistance while hyperplasia is linked to insulin sensitivity. There is more focus on hypertrophy as insulin resistance is a factor in so many diseases.

The idea that fat cells, adipocytes, are able to send signals to other cells, cytokines - which when made by adipocytes are adipocytokines or adipokines, is relatively new and a huge area of research. Hundreds of adipokines have been discovered but the understanding of them is limited. The view of fat tissue has changed from merely storage for excess energy to that of an incredibly complex endocrine organ because energy is fundamental to everything from powering muscles, brains and immune responses to growing new cells, growing cancers, growing babies, etc. Here is a recent paper that summarizes a lot of research on fat expansion and adipokines.

Fat cells can suppress hunger through the adipokine leptin. It’s possible that empty fat cells produce a hunger inducing adipokine or maybe they soak up fuel at the slightest hint of insulin leading other tissues to signal hunger.

I know very little about why fat cells die. One process is apoptosis, which is cellular self destruction or voluntary suicide and another is necrosis which is death from external injury. My guess is apoptosis plays a bigger role in reducing excess fat cells. The average lifespan of a fat cell is roughly 10 years so one could expect to lose roughly 10% of excess fat cells per year due to natural turnover alone. Cold stress and fasting can turn on genes for surviving lean times and may be key in quicker turnover of adipose tissue through apoptosis or other processes.


(Cathrine Helle) #20

I found this study that compares insulin resistant and insulin sensitive obese individuals. Have just read the excerpt, but will try to digest the whole thing. I hope it doesn’t have too many carbs :stuck_out_tongue: