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Antidiabetic effects discovered in the appetite hormone CART

Researchers at Lund University in Sweden have discovered that the appetite hormone CART is regulated by glucose and is found in greater quantity in people with type 2 diabetes.
“This could be the body’s own defence mechanism to lower blood sugar levels in case of type 2 diabetes”, says Associate Professor Nils Wierup, in charge of the study.

The study shows that the appetite hormone CART not only controls the sensation of satiety, but it also helps increase insulin secretion and decrease glucagon production.

CART (Cocaine and Amphetamine-Regulated Transcript) is a hormone that has mainly been studied in the brain’s centre for appetite control.

The research group behind the new study made the previously unknown discovery that CART can also be found in human alpha and beta cells located in the pancreas, and that cells from people with type 2 diabetes contain more CART than cells in people who are healthy.

“The high glucose levels could be what triggers the production of CART”, says Nils Wierup.

The study also shows that CART increases the effect of GLP-1, an intestinal hormone that lowers blood sugar levels. GLP-1 represents the basis of the latest drugs against type 2 diabetes by stimulating the body’s own insulin production.

Nils Wierup says that the new discoveries can eventually lead to new drugs against type 2 diabetes. However, because CART is currently only available for research purposes, the active molecule of the hormone needs to be further developed to create the equivalent effect artificially. Furthermore, the receptor that binds to the molecule is still unknown.

“However, we believe that we’re getting close”, says Nils Wierup and continues: “Once we find the unknown receptor, we hope to explain the biological mechanisms behind CART’s function, which will hopefully lead to new and better drugs.”

The findings are published in the scientific journal Diabetologia.

Facts/Insulin and glucagon

Insulin and glucagon are both hormones regulating blood sugar levels. The concentration of glucose, i.e. sugar, in the blood increases when you eat. Insulin is produced in beta cells and released in response to glucose to help the body’s cells to absorb glucose, thereby serving as a hypoglycaemic agent.
Glucagon is produced in the alpha cells, and, in contrast to insulin, it raises blood sugar levels. Together they work to stabilise the blood sugar level. In case of diabetes, the function of the beta cells is disrupted, which explains why the blood sugar level becomes too high.
 

Link to the publication

CART is Overexpressed in Human Type 2 Diabetic Islets and Inhibits Glucagon Secretion and Increases Insulin Secretion.

Abels M, Riva M, Bennet H, Ahlqvist E, Dyachok O, Nagaraj V, Shcherbina L, Fred RG, Poon W, Sörhede-Winzell M, Fadista J, Lindqvist A, Kask L, Sathanoori R, Dekker-Nitert M, Kuhar MJ, Ahrén B, Wollheim CB, Hansson O, Tengholm A, Fex M, Renström E, Groop L, Lyssenko V, Wierup N.
Diabetologia. 23 June 2016.