The alteration of the transport of leptin, the hormone of satiety, contributes to disrupt the secretion of insulin and promotes the onset of diabetes.
- Leptin is transported to the brain by cells called tanycytes to which it attaches via receptors called LepR.
- It is during this altered transport to the brain that partly explains the dysfunctions in the regulation of appetite in obese or overweight people.
- The absence of the LepR receptor disrupts the secretion of insulin and promotes the overflow of glucose which causes type 2 diabetes.
Leptin, otherwise known as the satiety hormone or appetite suppressant hormone, is a hormone secreted by adipose tissue depending on the fat reserves in the body. Its role is to regulate appetite by controlling the feeling of satiety. In a new study, published this Monday, August 2 in the journal Nature MetabolismFrench researchers from Inserm have discovered that its deregulation modifies the secretion of insulin and promotes the onset of diabetes.
Without a receptor, fat mass increases
Leptin is transported to the brain by cells called tanycytes to which it attaches via receptors called LepR. It is by this process that the hormone manages to cross the blood-brain barrier and to deliver satiety information to the neurons. Previous research has shown that it is precisely during this transport to the brain that is altered in obese or overweight people and which partly explains the dysfunctions in the regulation of appetite.
In this new research, scientists took a closer look at the role of LepR receptors. In mouse models, they observed what happens in the absence of these receptors. After three months, they found that the mice’s fat mass had doubled while muscle mass had halved.
Altered leptin transport implicated in the development of type 2 diabetes
Additionally, the researchers noted that, to maintain normal blood sugar levels, the mice secreted more insulin during the first four weeks of the experiment. Three months after receptor removal, their ability to secrete insulin from the pancreas appeared exhausted. These characteristics show that the mice have developed a pre-diabetic state. “In the longer term, the mice become unable to secrete insulin and therefore to control the amount of glucose present in the blood.the researchers wrote. These data thus suggest that an altered transport of leptin to the brain, via LepR receptors, is involved in the development of type 2 diabetes..”
Normally, blood sugar rises after ingesting glucose, before falling to help it enter the body’s cells. Without the LepR receptor, blood sugar displays abnormally high fasting levels that increase further after glucose ingestion. This renders the pancreas unable to secrete the necessary insulin and it becomes non-functional.
Leptin essential to the brain
Finally, the researchers reintroduced leptin into the brain to observe the body’s reaction. This caused an immediate resumption of its action and that of the pancreas, which immediately regained its ability to secrete insulin to regulate blood sugar. For the mice, this allowed them to have a healthy metabolism again.
“We show on the one hand that the perception of leptin by the brain is essential for the management of energy homeostasis and glycaemia. On the other hand, that blocking the transport of leptin to the brain alters the proper functioning of neurons that control insulin secretions from the pancreas”, concludes Vincent Prévot, director of research at Inserm, the last author of the study.
.
