Type 2 diabetes may originate in intestines

Type 2 diabetes and problems controlling blood glucose may originate in the intestines, according to researchers at Washington University School of Medicine in St. Louis.

Scientists studied mice that cannot produce fatty acid synthase (FAS) in the intestine. FAS is an enzyme necessary for the production of lipids and is regulated by insulin. People with type 2 diabetes have defects in FAS.

The researchers found that mice unable to make the FAS enzyme developed chronic inflammation in the gut, known to be a strong predictor of diabetes.

Inadequate intestinal lining

Upon close inspection, researchers found that the mice with a defect in FAS had lost the protective lining of intestinal mucus, called Muc2, that separates the gut microbes from direct exposure to cells. FAS is required to keep the mucosal layer intact and protects the colon and small intestine.

The loss of the mucosal layer allowed bad bacteria to penetrate otherwise healthy cells in the guts of the mice. This caused weight loss, diarrhea, and other gastrointestinal symptoms.

Clay F. Semenkovich, MD, lead researcher in the study, explained:

“Diabetes may indeed start in your gut,” “When people become resistant to insulin, as happens when they gain weight, FAS doesn't work properly, which causes inflammation that, in turn, can lead to diabetes.”

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Inflammation and insulin resistance - a bad combination

Inflammation and insulin resistance reinforce each other, according to the study. Inflammatory substances can cause insulin resistance, and insulin resistance is known to promote inflammation.

Scientists have long looked to the pancreas and liver for the underlying causes of diabetes since the pancreas produces insulin and the liver stores sugar. This new research suggests that diabetes originates in the intestines.

The researchers found gastrointestinal effects in the mice resembling some features of inflammatory bowel disease, and many people with diabetes develop gastrointestinal issues.

“Abdominal pain and diarrhea are some of the most common problems we see in people with diabetes,” said Semenkovich. “We could only connect these 'dots' because other experts at the university could help us link what we observed in these mice to what occurs in patients with diabetes and inflammatory bowel disease.”

A paper on the research study appears in the Feb. 16 issue of the journal Cell Host & Microbe.

Source: University of Washington School of Medicine