Link Between High-fat Diet and Type 2 Diabetes

Eating such food every day may
lead to diabetes; © Hemera

The researchers found out that knocking out a single gene encoding the enzyme GnT-4a glycosyltransferase (GnT-4a ) disrupts insulin production. Importantly, the scientists showed that a high-fat diet suppresses the activity of GnT-4a and leads to type 2 diabetes due to failure of the pancreatic beta cells.

The new studies suggest that people with an inherited predisposition to type 2 diabetes might have variations in the gene for GnT-4a. The researchers began their studies hoping to learn more about the function of protein glycosylation in the pancreas. They focused on the function of GnT-4a, in part, because it is highly expressed in the pancreas.

GnT-4a was known to maintain glucose transporters on the surface of beta cells in the pancreas. Those transporters, such as Glut-2, play a crucial role in allowing the beta cell to sense how much glucose is in the blood. Transport of glucose across the cell membrane into pancreatic beta cells triggers insulin secretion.

The new studies showed that in the absence of sufficient GnT-4a enzyme, Glut-2 lacks an attached glycan that is required for it to be expressed at the cell membrane. Without that glycan, Glut-2 leaves the cell surface and becomes internalised, where it can no longer transport glucose into the cell. In turn, this failure impairs insulin secretion, causing type 2 diabetes in the mice.

"What was really astounding to us, however, was that when we fed normal mice a high-fat diet, we saw this same mechanism of pathogenesis with attenuation of GnT-4a enzyme levels, reduced Glut-2 glycosylation, and loss of cell surface Glut-2 expression," said Marth.

The discovery of the link between diet and insulin production offers new information that may aid in the development of treatments that target the early stages of type 2 diabetes.; Source: Howard Hughes Medical Institute