Accelerated intestinal glucose absorption in morbidly obese humans – relationship to glucose transporters, incretin hormones and glycaemia
Another study showing that obese people have rapid and increased glucose absorption from the duodenum due to increased glucose transporters. This rapid glucose absorption facilitates hyperglycemia and hyperinsulinemia, because as we know, faster digesting carbs spike blood sugar and insulin more aggressively.
Although it has long been thought that the hyperglycemia and hyperinsulinemia in obese people is due to insulin resistance, the authors here question this, and speculate that rapid glucose absorption could instead easily account for this.
Further there is an imbalance of postprandial incretin hormones, obese people exhibit reduced GLP-1 secretion in response to carbs, ( which is also seen in the graphs here ), the authors here mention that reduced GLP-1 secretion allows glucagon secretion to be enhanced in the postprandial state, which is very inconvenient when combined with the hyperglycemia from the food ingested, because the job of glucagon is to raise blood sugar ( and its already raised from the food ) The combination of enhanced glucagon levels AND the carbs results in even HIGHER blood glucose, and you need even HIGHER insulin to deal with it. Something of a vicious cycle.
We know way back from the powdered carbs study that there is something about the digestibility of carbohydrates that can SERIOUSLY enhance how fattening they are. Indeed it seems to be refinement of carbs that makes them more easily and quickly digested that is the devil. The obesity epidemic has risen in parallel with refined carb consumption.
How hard would it be to believe that...
refined carbs -> morphological changes to intestine** -> hyperglycemia + hyperinsulinemia in response to carbs -> adipogenesis + histone acetylation in fat tissue -> elevated fat mass setpoint -> obesity + resistance to weight loss
There is already some evidence hyperglycemia can cause chromatin remodeling to DNA.
**to the best of my knowledge, this has never been investigated, so we dont know if its true, or false. I.E. if the refinement of dietary carbs can directly cause elevated glucose transporters in the duodenum.
The speculation about possibly enhanced duodenal glucose transporters is very interesting.
ReplyDeleteYour talk of carb refinement/digestibility reminds me of this paper "Comparison with ancestral diets suggests dense acellular carbohydrates promote an inflammatory microbiota, and may be the primary dietary cause of leptin resistance and obesity”. You might find it worth your time.
I think the causality pathway you outlined here is correct but I see it as an extension/refinement of the causal chain, not as an overturning of "...hyperglycemia and hyperinsulinemia in obese people is due to insulin resistance…”. The latter simply points to the tipping-point variable (insulin) as being primarily responsible for the actual accumulation of FAs in adipose cells. Your/the papers' causal chain simply place refined CHO as the prime external candidate capable of triggering that deciding variable (insulin). That makes all the sense in the world. However, it seems like insulin is still ‘central’ because (for e.g.) circadian timing could replace refined CHO & your causal chain would still make total sense.
I don’t think it's semantics - actually, the morphological changes to the intestine might be a proxy marker for CHO-induced IR &/or adipocyte enlargement/proliferation. It’d be helpful to distinguish between other sources of IR or manners in which adipocytes make become dysregulated.
We know from Bill’s last post how important circadian timing is acetylating/deacetylating histones