Alternate Path to Satiety
Now comes study in the New England Journal of Medicine issue March 18 on Semaglutide, a diabetes medicine which along with healthful diet and exercise induced a near 15% average weight loss in overweight subjects. This is a once a week injection given at high dose, one of a class of diabetic drugs called glucagon like peptide 1 agonists (GLP-1 agonist). You may recognize their generic names ending in, “tide.”
GLP-1 is an incretin meaning a small peptide leading to decreased glucose and increased insulin levels. GLPs-1s excite the neurologist by virtue of a widespread signaling effect and presence in gut and brain, in the brain associated with the nucleus solitarius. This group of brain cells sub serves taste sensation thus related to eating. The appetite center of the brain though is the hypothalamus. In recent years scientists have uncovered a good number of molecular signals affecting satiety, among these ghrelin, leptin, and GLP agonists.
On the most fundamental level, the obese differ from the rest of us in their being always hungry. The over-nourished may be as hungry as the malnourished. Given the chance overweight people consume more food. If medical science finds a way to reduce appetite to satisfy cravings, that is going to be the holy grail for treatment of obesity.
GLP-1s or incretins appear after a meal and deactivate quickly. They provide the quintessential signal for gut and brain. They enhance insulin secretion, slow the movement of food in the stomach thus preserving gastric dissension and increase hypothalamic medicated satiety. Thus they diminish food consumption.
More interesting, is their neurotrophic effect. Insulin is made by beta cells in the pancreas. Incretins or GLP-1s signal pancreatic beta cells to secrete more insulin and to proliferate. Beta cells become less likely to die what is called a trophic effect. Thus GLP-1s may possibly lead to enhanced diabetic control in the long run.
But the piece de resistance is that GLP-1s may diminish pathways of neuronal cell death such as occurs in degenerative conditions such as Alzheimer’s, Parkinson’s and may even prove useful in Huntington’s chorea, degenerative conditions of the brain. Thus do pathways of satiety and all other signals interconnect in one vast skein.
Bill Gates makes the argument, play your cards right and technology may just save us from ourselves, from the terrible dystopia of global warning. Technology may save us from the ravages of aging. Here, neuronal degeneration, aging and sugar handling mechanisms intersect. Alzheimer’s is type 3 diabetes. As in Walt Whitman, the blade of grass thoughtfully considered relates to everything.