Type 2 diabetes is an increasingly frequent pathology, the management of which is complex. This pathology essentially involves a reduction in insulin secretion which remains difficult to improve. This is why finding new treatments for improve diabetes balance in the long term and in particular the secretion of insulin eis an important objective in this field. As Inserm explains, it has been several years since it has been proven that a type of bariatric surgery as an effective treatment for severe obesity called “Gastric bypass” could, before any significant weight loss, improve or even make disappear type 2 diabetes.
This technique makes it possible to reduce both the quantity of food ingested (the size of the stomach is reduced to a small pocket) and their assimilation by the body, thanks to a short-circuit of part of the stomach and intestine (no organ is removed). Thus, food goes directly to the middle part of the small intestine and is assimilated in smaller quantities. If studies have already shown specific effects of this surgery on insulin secretion regardless of weight loss, effects which are not otherwise found in techniques without anatomical change in the intestine (gastric ring), the underlying mechanism is poorly understood.
Secretion of the hormone GLP-1, the key to the mechanism
It is known that weight loss is associated with better glycemic control in the event of Type 2 diabetes. But surprisingly, why do people with obesity and diabetes who have surgery see their blood sugar levels improve long before they lose weight? This is the question that researchers from Inserm wanted to answer, who wanted to know more precisely why this surgery has an effect on blood sugar levels independent of weight loss. The scientific team took as a starting point a specific hormone called “GLP-1” Involved in the control of blood sugar, this hormone is therefore secreted after each meal.
“This hormone then stimulates the release of insulin and reduces the risk of hyperglycaemic peak by slowing the passage food in the intestines and therefore the speed of absorption of nutrients including glucose ”, specify the researchers, whose study is published in Nature Communications. But it turns out that in obese patients who have operated on, this hormone is found in abnormally high quantities in the blood. They therefore decided to study its secretion in different situations, in animals and humans. Since bariatric surgery relies on the elimination of part of the stomach, researchers suspected the existence of changes in its level.
Increased production by the stomach
Researchers previously believed that the secretion of this GLP-1 hormone mainly took place in the colon and ileum (terminal part of the small intestine that precedes the large intestine), the team found that cells that produce the hormone were naturally present in the stomachs of thin rats, releasing the hormone in small amounts. “If these rats become obese, the cells in question lose their sensitivity to glucose and the production of GLP-1 dries up. But when they remove part of their stomach, these cells start to proliferate and become sensitive to glucose again, leading to an increase in the level of circulating GLP-1, capable of acting in the gastric area ”, they note.
“It may seem paradoxical: we are removing part of the stomach and oddly enough, the GLP-1 producing cells start to function again and their quantity increases. There is in fact a remodeling of this organ after surgery, a real reprogramming of its cellular composition ”, indicates Maude Le Gall, who led the study. “It sometimes re-increases in size and, above all, it is enriched in functional GLP-1-producing cells, capable of improving blood sugar control. These data were subsequently confirmed in humans, using gastric and intestinal tissue samples from patients at Bichat and Louis-Mourier hospitals.
The next step for the scientific team will be to discover the biological link between this remodeling of the stomach and surgical intervention. In addition, the latter considers that this discovery does not exclude the existence of other so-called “hypoglycemic” mechanisms induced by surgery. “Other surprises may therefore remain to come,” she concludes. It should be noted that according to statistics from the Academy of Medicine, the number of patients having benefited, in France, from bariatric surgery has tripled between 2006 and 2014, from 15,000 to 46,911 per year. But the organization considers that the monitoring of patients in the medium and long term is very insufficient.