I have a lot of ideas and theories about hormones which are (hopefully) not that esoteric and pertain directly to a lot of people with certain health conditions. I want to record them before I forget 'em.
My first idea is about diabetes, and has a lot to do with the concepts of down-regulation and negative feedback. First, hormones are extremely potent, causing big effects despite being present in extremely low quantities in serum. Hence, in the presence of dangerously elevated hormone levels, cells will decrease the number of receptors to that hormone on their exterior surfaces, so they become less responsive to the hormone. That's down-regulation. And in the presence of high levels of circulating hormone, the body will tend to produce less of that hormone. That's negative feedback. These are both healthy, normal compensatory mechanisms.
I think diabetes is better understood in light of these two concepts. If humans eat only when they're hungry, their blood sugar levels rise and fall periodically throughout the day. Following that, insulin levels rise and fall. But continual overingestion of starches and sugars can lead to a constantly high glucose level—and therefore a constantly high insulin level. Now, insulin is a potent hormone. It pushes serum sugar into cells (and shifts potassium too, right?). You can inadvertantly kill someone with insulin. So people with diabetes undergo a usually healthy compensatory response by making less insulin and becoming more resistant to insulin. In other words, they've down-regulated (reduced the number of insulin receptors) and have undergone negative feedback (reduced their production of insulin). The cells don't care if blood sugar levels are high, as long as they protect themselves from the high levels of circulating insulin and glucose.
This is why diet and exercise are so effective at relieving diabetes if it is not too far progressed. I remember thinking all diabetics had to inject insulin three times a day; that's not true at all. Many diabetics have up-regulated their insulin receptors and decreased that negative feedback response by diet and exercise (albiet often with the help of oral antidiabetic meds which boost insulin production or decrease glucose production).
When diabetes becomes extreme, it will down-regulate receptors and reduce insulin production so much that even in the presence of extreme hyperglycemia (high blood sugar), the body will enter a starving response, metabolizing the body's own proteins and fatty acids just to stay alive, producing potentially lethal amounts of acidic by-products in the blood (diabetic ketoacidosis).
In the hospital, and in acute cases, we inject exogenous insulin to push all that sugar into the cells regardless of whether the cells want it. My question is, does this do anything bad to the cells? I assume the cells have down-regulated for a reason. If they had the capacity to bring a 400 or 600 glucose level down to 100 just by storing infinite amounts of glucose, they would already do it, and we wouldn't have to force it with insulin. So what does this do to the various cells of the body? Anything? I'm not saying, of course, that we should avoid giving insulin for acute high blood sugar or brittle (unresponsive) diabetes; we have clear evidence of the harm that would cause. But I'm curious if research will eventually show any evidence of intracellular damage: i.e. DNA alteration, malignancy, etc.
Insulin image by Isaac Yonemoto.
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