Wooo has posted a couple of times about Dr Shawn Baker who eats an all meat, very high protein diet, maybe over 400g/d protein intake. His HbA1c is reported as 6.3%. Personally I have absolutely no interest in this style of eating but the underlying mechanism is obviously interesting.
How about this for a hypothetical marked protein ingestion scenario:
A person eats a lot of meat. In response to the insulinogenic amino acids present they secrete insulin. This will be amino acid specific, I’ve not looked in to how amino acids trigger insulin secretion in detail but it will NOT be through pancreatic glucokinase and subsequent glucose metabolism, as is the case for glucose triggered insulin secretion. So they secrete post prandial insulin but not using glucokinase. The insulin will be exactly in balance with the glucagon for that specific protein meal.
The expression of the gene for generating pancreatic glucokinase is controlled by the carbohydrate content of the diet. Glucose means glucokinase is required. All amino acid diet, no glucose, down-regulate glucokinase.
So, as glucose is subsequently and gradually produced from gluconeogenic amino acids and then released from the liver over several hours (in the presence of only basal insulin), there is only a mild glucose derived stimulus to trigger insulin secretion, and this slow release of glucose by the liver also provides only a minimal drive to express the gene for pancreatic glucokinase. Also hepatic glucose output shouldn’t trigger any of the gut derived insulin secretion potentiating hormones (GLP-1 and the like).
So pancreatic glucokinase is mothballed. Modest glucose release from protein metabolism won’t trigger insulin secretion without the glucose sensor. End result is low insulin with moderately elevated glucose, especially during the time protein is being processed. Which I'd guess is pretty well all of the time on greater than 300g/d. How high should glucose go? High enough to allow a slow trickle to be taken up by constitutive transporters and so deal with hepatic glucose output in this way, without insulin facilitated augmentation. Facilitated by exercise if you like that sort of thing.
How toxic is glucose in the absence of hyperinsulinaemia, given that HbA1c over 6%? Dr Baker will let us know over the next 15 years!
Of course exactly the same happens on LCHF eating, just fat does not provoke chronic glucose release from its metabolism outside of a little glycerol derived gluconeogenesis… It probably happens too in some of the weird sucrose based weight loss diets where the mice (it's mostly mice but we all know that you can do "carbosis" in humans too) are hypoinsulinaemic (otherwise they would be fat!) but glucose intolerant. A diet based on a non-insulinogenic sugar (fructose) and its palmitate derivative will mothball pancreatic glucokinase too.