High-fat diet leads to type 2 diabetes

Protect your health by eating a low-fat or moderate-fat diet. Low fat means under 20% of calories from fat. Moderate fat means under 30% of calories from fat. Fat has 9 calories per gram; carbohydrates and protein have 4. So by weight low-fat is under 10% fat in your food and moderate is under 15% fat. Eat less cheese and more vegetables.

Howard Hughes Medical Institute researchers have discovered a molecular link between a high-fat, Western-style diet and the onset of type 2 diabetes. This research helps to explain the recent rise in type 2 diabetes in North America.

In studies in mice, the scientists showed that a high-fat diet disrupts insulin production, resulting in the classic signs of type 2 diabetes. Their article appears in the December 29, 2005, issue of the journal Cell.

The researchers report that knocking out a single gene encoding the enzyme GnT-4a glycosyltransferase (GnT-4a) disrupts insulin production. They also showed that a high-fat diet suppresses the activity of GnT-4a, causing failure of the pancreatic beta cells and leading to type 2 diabetes.

“We have discovered a mechanistic explanation for beta cell failure in response to a high-fat diet and obesity, a molecular trigger which begins the chain of events leading from hyperglycemia to insulin resistance and type 2 diabetes…..” (What follows is my translation of the rest of the announcement.)

In its earliest phases, type 2 diabetes causes failure of the insulin-secreting beta cells, which leads to high levels of glucose in the blood. Later in the disease, the beta cells overcompensate for the high glucose levels and eventually pump out too much insulin. This leads to insulin resistance and full-blown type 2 diabetes.

Normally, the beta cells in the pancreas secrete insulin, which lowers glucose levels. The beta cell detects glucose when proteins called glucose transporters carry glucose across the cell membrane into the cell. Glucose in the beta cell triggers it to secret insulin.

The researchers focussed on a glycosyltransferase enzyme called GnT-4. Glycosyltransferases attach sugar-like molecules called glycans to proteins. Many proteins need glycans to function properly. In particular, the enzyme GnT-4a attaches glycans that maintain glucose transporters on the surface of beta cells in the pancreas. One of those transporters is the protein Glut-2.

Without the GnT-4a enzyme, Glut-2 is missing an attached glycan that it needs to stay at the cell membrane. The Glut-2 molecule sinks into the cell surface, whence it can not transport glucose into the cell. No longer sensing glucose, the beta cells secrete less insulin, causing type 2 diabetes in the mice.

The researchers found that the whole disease process could be started by a high-fat diet. “….when we fed normal mice a high-fat diet, we saw this same mechanism of pathogenesis [disease creation].”

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