Download Expanding the Field of Diabetes Research Diabetes May Originate

Expanding the Field of Diabetes Research
Diabetes May Originate in the Intestines
While the role of the pancreas and the liver in the
development of diabetes are well described, a recent study
conducted by American Diabetes Association-funded
researchers at Washington University in St. Louis suggests
that the digestive system may also play a surprising and
important role in developing the disease.
Lead investigator Clay F. Semenkovich, MD is the main
author on the February 16, 2012 Cell Host & Microbe
publication, which links an insulin-regulated enzyme, called
fatty acid synthase (FAS), to chronic inflammation in the
gut—a known contributor to insulin resistance and type 2
diabetes. Dr. Semenkovich’s former postdoctoral fellow in
an Association mentorship grant, Xiaochao Wei, PhD,
collaborated on the study and is first author on the paper.
From left: Xiaochao Wei, PhD; Clay F.
Semenkovich, MD
While humans (and animals) depend on normal gut bacteria to aid with digestion and help produce
vitamins, a protective mucus barrier prevents harmful pathogenic bacteria from invading the small
intestines and colon. The scientists found that FAS, an enzyme which is critical in lipid and fat
production, helps maintain this protective mucus membrane that lines the intestines. Since FAS is
regulated by insulin, people with diabetes have lower levels of the enzyme and thus may be more
vulnerable to inflammation in their digestive tract.
Dr. Semenkovich and Dr. Wei observed that mice with diabetes have weakened mucus barriers that
allowed their intestines to become more permeable to inflammatory pathogens. By treating the
animals with insulin, the researchers were able to increase FAS levels, restore the mucus layer, and
decrease intestinal permeability.
"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," said Dr. Semenkovich. By identifying new mechanisms involved in the development of
diabetes, these results could provide future avenues for developing therapeutics to combat the
disease. Dr. Semenkovich currently holds two active grants with the American Diabetes Association
and continues to mentor a new fellow, Mariko Johnson, MD, who is exploring related mechanisms.
"These awards continue to make it possible for me to identify and nurture the careers of young
scientists who hope to improve the quality of life for people afflicted with diabetes."
(Wei X, Yang Z, Rey FE, Ridaura VK, Davidson, NO, Gordon JI, Semenkovich CS. Fatty acid synthase modulates
intestinal barrier function through palmitoylation of mucin2. Cell Host & Microbe, Feb. 16, 2012.)