In the Body, It Regulates Blood Sugar; in the Brain, It Regulates Appetite... Insulin's 'Two Jobs' [Professor Ahn Cheol-woo's Hormone Encyclopedia]

[Financial News]Hormones have evolved alongside life itself and have been passed from species to species. If there is a chemical that must exist as long as life exists, it is hormone. In that sense, hormones are immortal. Through this column, Professor Ahn Cheol-woo aims to explain the hormones that govern the body and suggest ways to live a healthier and happier life.  

What exactly does insulin do in the brain?
As a peripheral hormone, insulin lowers blood sugar by moving glucose in the bloodstream into cells. In the brain, however, even flooding it with insulin does not lower glucose levels. In addition, glucose transport proteins GLUT1 and GLUT3 are needed to deliver glucose to various neurons and nuclei in the brain, and insulin is not involved in that process.
A 1979 study provided the clue. When insulin was directly administered into the ventricles of baboons over a long period, their food intake dropped sharply and they lost a great deal of weight.
A similar result was seen in a 1991 experiment on marmots. Marmots hibernate in winter and eat voraciously in summer. When insulin was administered into their ventricles for an extended period during the summer, they ate less and lost weight.
This is a result that can never be obtained by injecting insulin into humans intravenously. Blood insulin levels do not affect human appetite at all.
In 1998, researchers at the Royal Adelaide Medical School in Australia intravenously injected multiple doses of insulin into 14 fasting young men and women, then let them eat as much as they wanted at a buffet restaurant for 30 minutes. The result showed no causal relationship between the amount they ate and the insulin dose.
These findings show that insulin has nothing to do with appetite in the body and serves only to lower blood sugar, while in the brain it is unrelated to blood sugar and functions to suppress appetite.
If this principle were used for dieting, we could control appetite effectively without worrying about blood sugar dropping.
In fact, in 2012, a research team from the Department of Neuroendocrinology at the University of Lübeck in Germany succeeded in reducing the desire for snacks and lowering snack intake by administering insulin through the noses of women who had finished eating. The insulin delivered through the nose slightly lowered plasma glucose levels, but it did not affect blood insulin levels.
If this method can actually be applied to dieting, it would be tremendous news for diabetic patients who need to lose weight while avoiding hypoglycemia.
In the end, insulin's role in the brain is to suppress appetite. In the body, it keeps blood sugar from rising too high, and in the brain, it suppresses appetite so we do not overeat.
But insulin is not the only factor that affects appetite. Leptin, secreted by fat cells, and ghrelin, secreted by the stomach, also act on the brain's appetite-control system.
There is another powerful appetite-stimulating system we know well: the dopamine reward system. It gives us pleasure and exhilaration when we satisfy hunger and feel full. That becomes a form of learning and motivation, driving us to search hard for food when we are hungry.
However, according to a paper published in 2021 by the Diabetes, Metabolic Diseases Research Center at Tübingen Medical School in Germany, insulin was found to affect the dopamine reward system. The research team injected insulin through the noses of 10 healthy men of normal weight and used magnetic resonance imaging to capture changes in the brain.
As a result, they observed a decrease in dopamine levels in the striatum and changes in the brain's active circuits. Perhaps insulin suppresses appetite by influencing the dopamine reward system.
The way insulin interacts with leptin and ghrelin in the brain also affects appetite. Leptin is secreted by fat cells and ghrelin by the stomach, but their target cells are the same: the arcuate nucleus of the hypothalamus. Leptin is released when we feel full and binds to receptors in the arcuate nucleus.
The arcuate nucleus then sends various neurotransmitters and hormones throughout the brain to suppress appetite, raise body temperature and blood pressure, and increase cellular metabolism. Because leptin sends this signal to stop eating, we can put down our spoons once we feel full after eating a moderate amount.
By contrast, ghrelin is secreted when there is no food in the gastrointestinal tract and binds to receptors in the arcuate nucleus. The arcuate nucleus then releases various signaling proteins and hormones, making us feel hunger and appetite. At the same time, the parasympathetic nervous system is activated and cellular metabolism decreases.
Although leptin and ghrelin have opposite functions, it is difficult to say they simply act as antagonists. Leptin is less a hormone that responds immediately to fullness than one that broadly regulates body fat and appetite.
Ghrelin, on the other hand, is a hormone that responds immediately to hunger and disappears quickly. People who are born without the leptin gene cannot feel full. They are constantly plagued by hunger, keep eating, and become severely obese. In addition, without leptin, gonadotropin-releasing hormone secreted from the hypothalamus is not produced properly, so sexual development also fails to progress. By contrast, the ghrelin gene is encoded together with another hormone called obestatin.
Interestingly, when ghrelin signals hunger and makes us want food, obestatin prepares us to eat less. It slows the rate at which food is digested and the stomach is emptied, thereby stopping ghrelin secretion. If a person is born without the ghrelin gene, they become extremely tall and obese. That is because this hormone stimulates the secretion of growth hormone-releasing hormone in the hypothalamus.
/Ahn Cheol-woo, Professor of Endocrinology, Gangnam Severance Hospital


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