It is generally agreed that insulin secretion increases as blood glucose increases, and the same is true for islets/beta-cells in a dish in response to glucose. I have been trying to locate definitive findings in the literature of what the glucose dose-response curve for insulin secretion looks like for rodent and/or human islets across a broad range of glucose concentrations (0-200 mM or more). At what glucose load does insulin secretion max out? My impression is that the range is far broader than I would have expected. Does secretion remain steady beyond this peak value or does it actually diminish if glucose loads become too high, thus creating the inverted U-shaped curve? I would greatly appreciate citations or links to well accepted publications on this matter.
I am not sure about insulin secretory response of islets, pancreas (in isolated organ perfusion) or in vivo at glucose concentrations that exceed too far beyond 25mM. I am not certain why you are interested in concentrations of glucose that are far too high, way beyond what may be physiologically relevant (200mM or higher - hypersonic by itself).
In general, in case of isolated islets or pancreas, continued perfusion with high glucose (20-25mM glucose) will result in a biphasic insulin secretion; first sharp peek, followed by a plateau of insulin secretion for some time (10-15 min) but then the level may gradually decrease. From the perspective of normal physiology, this is expected because in response to hyperglycemia, insulin is secreted which results in lowering of blood glucose and insulin secretion goes back to basal level. In response to sustained hyperglycemia, islets will gradually deplete of their reserves and finally the insulin secretion will diminish.
Dear Tausif,
Your response matches rather closely with what I teach in my lectures on basic beta-cell physiology. I don't exceed 28 mM glucose for my studies either because that's a plenty high concentration to maximize insulin release and reach the top of the glucose dose-response curve, right? Apparently, not. The few peer-reviewed studies I have been able to find suggest 50-200 mM glucose to reach maximum insulin secretion--much, much higher than I would have expected.
I was eliciting help in finding a well-cited publication that includes a proper dose-response curve for insulin secretion in response to glucose stimulation. Sometimes Pubmed can be a bit unwieldy for this purpose.
Also, while I don't view 200 mM glucose as physiologically relevant either, it made me ask myself what is the highest blood glucose level a pancreas might see. I found this in the Guinness Book of World Records... "Michael Patrick Buonocore (USA) (b. 19 May 2001), survived a blood sugar level of 147.6 mmol/L (2,656 mg/dl) when admitted to the Pocono Emergency Room in East Stroudsburg, Pennsylvania, USA, on 23 March 2008."
I believe this was a transient event in a child upon diagnosis with type 1 diabetes, but the previous record was in the same range, so it really makes one marvel at the limits of the human body!
Anyway, thanks for your response. Hopefully, I will track down a publication or two eventually.
Hello Craig,
Although it seems possible that an undiagnosed child, soon after having a rather large amount sugar (dessert) could reach a transient peak of glucose levels that seem surprisingly high but I am somewhat skeptical of levels approaching 150mM to occur with any degree of regularity, even if transiently.
Just to go over the numbers, to attain a blood glucose level of 2,500mg/dl, a child of 20kg will have to consume 500gm of glucose, assuming 100% transport to blood through the digestive system and assuming roughly 10% body weight as blood volume - this rough estimate does not include cellular or interstitial space.
I am not sure how oblivious a parent can be to let a child consume so much sugar but I suppose that there is always room for exceptional cases.
In our experimental untreated diabetic animals, we have noted blood glucose levels approaching 1000mg/dl (the glucometer used in such measurements has no upper limits of measurements due to the fact that the plasma can be diluted to any degree to keep the numbers in the reliable range of the standard relationship).
I never use glucose concentrations higher than 20.6 mM glucose in isolated beta cells. However if you add a depolarization concentration of K or a permeable analog of cAMP you will get much more secretion.
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