This study is one of the references in B.Corkeys paper very interesting paper in which she lays out the framework supporting the hypothesis that hyperinsulinemia is a likely cause of diabetes and obesity. In it, she says.....
Hyperinsulinemia also can cause insulin resistance through insulin-induced receptor down-regulation both in the periphery and in the brain where hyperinsulinemia-induced insulin resistance may abrogate insulin's role as a satiety signal.
If we now turn to the 1974 study linked above we see that chronic ( 5-16hr ) insulin exposure produces a decrease in insulin receptor concentrations. Meanwhile, acute exposure ( 0-2 hr ) was without affect. This seems to indicate that it is the fasting hyperinsulinemia causing the problems, and possibly not the acute insulin spikes in the postprandial state. Infact this is exactly what JJ talks about in his recent paper.
In JJ papers there is an emphasis on the basal hyperinsulinemia, that seems to be caused by beta cell growth. Thats probably exactly where elevated fasting insulin levels comes from, the beta cell proliferation and increase in beta cell mass.
But wait a minute, the acute postprandial insulin spikes aint off the hook yet. The burning question from JJ's paper is, what causes the increase in beta cell mass to begin with? What gets the ball rolling? Remember that we learnt from JJ's paper that insulin positively regulates the growth of its own secretory cells. Is it the acute postprandial insulin spikes then that sets us up for beta cell growth? Which in turn sets us up for fasting hyperinsulinemia?
One of Jane's comments in response to JJ's paper was that it seems to indicate that it is the absence of low insulin which is the problem. Looking at the data from the 1974 paper, Jane may have been more right than anyone would give her credit for.
Absence of low insulin ( i.e. chronic exposure ) keeps insulin receptors down-regulated, so when meal-time does eventually come around and you eat your potatoes, what do you think is gonna happen? Blood sugar spikes, insulin spikes, and suddenly we have all this glucose and insulin in our blood but we have less insulin receptors because of our chronic fasting insulin exposure, so the blood glucose takes longer to clear and we end up secreting even more insulin because our pancreas is panicking trying to keep our blood sugar under control. If you plot these events on a graph, youd be labelled as "glucose intolerant"
We may even experience decreased satiation because of down-regulation of the insulin receptors in the brain. Maybe!
I have another post coming up which further supports the idea that hyperinsulinemia comes before insulin resistance and that hyperinsulinemia may be the initial cause in type 2 diabetes.
In corkeys paper there is another passage worth mentioning, she says...
An elegant study by Sims et al in the 1970's found that experimentally overfed volunteers required nearly 6000 calories per day to maintain a 20% increase in bodyweight and most of these subjects rapidly returned to their normal weight at the end of the study when overfeeding ceased.
So to all those people out there who think over-eating causes obesity. The question is why didnt it more reliably cause obesity in the Sims et al study? If over-eating is such a strong cause of obesity, if over-eating is *sufficient* to produce obesity, then why does it not produce obesity in experimental over-feeding with a success rate of near 100%?
Either over-feeding is a cause, or, its not a cause. If its a cause, the success rate should be very high.
over-feeding, while it can cause *weight gain* ( which appears to be only temporary in most cases ), it does not reliably produce obesity. Remember obesity is not just defined as having a BMI > 30. Obesity is DEFINED by having a homeostatically defended elevated fat mass, and accompanying resistance to weight loss.