Type 2 First phase insulin, Metformin & GLP-1

ajbod said:

My simplified take on phases, is that when we eat the saliva contains Amylase which tells the system fuel is on the way. So the pancreas releases some Insulin to start working. Then when the body can better detect the levels of Glucose the second phase kicks in to regulate the blood sugar levels. Obviously with Insulin resistance the expected output of Insulin doesn't work as expected, so more is needed to do the job. Hence Hyperinsulimia. As type 2 our levels drop slower than they should as resistance means it takes longer to deposit the Glucose within the tissues.
This to my mind is why low carbing works so well , as we are reducing the Glucose load to a level our second phase response actually handles. Although we still have the slower drop of levels due to resistance, but an insufficient rise to kick in even more Insulin secretion.

Click to expand...

Nice explanation. The first phase is like a warning shot. While we are in fasting state, our beta cells charge up their internal granule based stores (insulin is stored as clusters of 6 molecules in a hexamer) and the amylase in saliva triggers the output portal to open and release this store. Then later, a second amylase release occurs in the duodenum that triggers the second follow on phase. This second phase is cyclic, i,e, close output portal, charge up the cell granule again then release it. Because the beta cells operate autonomously, the result appears to be continuous output but it is actually a pump/prime/release operation at the cellular level. This second stage is mainly controlled by GLP-1 which is the ON switch. The volume is controlled by sulfonylurea generated by the delta cells. The process turns off when GLP-1 is removed by the Alpha cells which are the ones controlled by glucose levels.

Even in fasting state our glucose levels fluctuate during the day, and there is a fluttering of GLP-1 that the alpha cells generate as bgl levels rise, and this is what is supposed to be the main control regime, and where the basal effect occurs. Type 2 due to insulin resistance means that the levels do not drop so there is a high demand for insulin to be produced to combat it. But our beta cells are rate limited so this limits the insulin we produce.

IMHO the claim that some meds lead to beta cell burnout is a misnomer, because in T2D we are already thrashing our betta cells. I suppose if your insulin output is already weak then those meds may increase the demand signal and make things worse. But I think beta cell demise is due to other causes. The ND study seems to show that ectopic fat in the pancreas is a severe limiter of insulin capacity. Low calorie or low carb diets seem to reduce this ectopic fat.

My limited understanding is that the first FAT to use is the glycogen store, which is topped up every time we eat. The second the ectopic fat, followed by the subcutaneous fat. So i think the ND diet works well with the ectopic fat, but as soon as subcutaneous fat starts going, (shown by waist level dropping). Then i think a switch to proper low carb would work much better, and reduce hunger and therefore be easier to stick to. But the problem there would be sales of shakes would stop, so that's not going to happen is it.