Navigation Links
Diabetes may start in the intestines, research suggests
Date:2/15/2012

Scientists at Washington University School of Medicine in St. Louis have made a surprising discovery about the origin of diabetes. Their research suggests that problems controlling blood sugar the hallmark of diabetes may begin in the intestines.

The new study, in mice, may upend long-held theories about the causes of the disease. Because insulin is produced in the pancreas and sugar is stored in the liver, many scientists have looked to those organs for the underlying causes of diabetes.

The findings are reported Feb. 16 in the journal Cell Host & Microbe.

In the new research, scientists studied mice that are unable to make fatty acid synthase (FAS) in the intestine. FAS, an enzyme crucial for the production of lipids, is regulated by insulin, and people with diabetes have defects in FAS. Mice without the enzyme in the intestines develop chronic inflammation in the gut, a powerful predictor of diabetes.

"Diabetes may indeed start in your gut," says principal investigator Clay F. Semenkovich, MD. "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."

First author Xiaochao Wei, PhD, and Semenkovich, the Herbert S. Gasser Professor of Medicine, professor of cell biology and physiology and director of the Division of Endocrinology, Metabolism and Lipid Research, collaborated with specialists in gastroenterology and genome sciences to determine what happens in mice that can't make FAS in their intestines.

"The first striking thing we saw was that the mice began losing weight," says Wei, a research instructor in medicine. "They had diarrhea and other gastrointestinal symptoms, and when we looked closely at the tissue in the gut, we found a lot of inflammation."

Initially, the researchers thought that the mice became sick because of changes to the mix of microbes that naturally live in the gut, where they help digest food and synthesize vitamins.

In collaboration with Jeffrey I. Gordon, MD, director of the Center for Genome Sciences and Systems Biology at the School of Medicine, they looked more closely at gut microbes in the mice.

"The mice had substantial changes in their gut microbiome," Semenkovich says. "But it wasn't the composition of microbes in the gut that caused the problems."

Instead, Wei says, the mice got sick because of a defect in fatty acid synthase. The mice without fatty acid synthase had lost the protective lining of mucus in the intestines that separates the microbes from direct exposure to cells. This allowed bacteria to penetrate otherwise healthy cells in the gut, making the mice sick.

In a further collaboration with Nicholas O. Davidson, MD, director of the Division of Gastroenterology, the researchers found gastrointestinal effects resembling some features of inflammatory bowel disease. Other investigators studying humans with ulcerative colitis had previously made the unexplained observation that colon biopsies from these patients have low amounts of fatty acid synthase.

AUDIO: Mice with defects in their ability to make the enzyme fatty acid synthase in their intestines develop inflammation, and diabetes. In a new study, Washington University researchers made the surprising...

Click here for more information.

"Fatty acid synthase is required to keep that mucosal layer intact," Wei says. "Without it, bad bacteria invade cells in the colon and the small intestine, creating inflammation, and that, in turn, contributes to insulin resistance and diabetes."

Inflammation and insulin resistance reinforce each other. Inflammatory substances can cause insulin resistance and inhibit the production of insulin, both of which interfere with the regulation of blood sugar. In turn, insulin resistance is known to promote inflammation.

Further study showed that the ability to build the thin, but important, layer of mucosal cells was hindered by faulty FAS.

That the gut is so important to the development of diabetes makes sense because many people with the condition not only have faulty FAS, but they also frequently develop gastrointestinal difficulties, Semenkovich says.

"Abdominal pain and diarrhea are some of the most common problems we see in people with diabetes," he says. "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," Semenkovich says.

Semenkovich and Wei say much more study is needed, but they say that FAS and a key component of the intestinal mucosa called Muc2 may be potential targets for diabetes therapy. They now plan to study people with diabetes to see whether FAS is altered in a similar way, producing damage to the mucosal layer in the intestines.


'/>"/>
Contact: Jim Dryden
jdryden@wustl.edu
314-286-0110
Washington University School of Medicine
Source:Eurekalert  

Related medicine news :

1. Neighborhood socioeconomic status and diabetes
2. NACDD Receives Two-Year Grant From Merck & Co., Inc. to Improve Diabetes Education
3. International Diabetes Federation awards $2 million to 9 global diabetes research projects
4. Diabetes drug ups risk for bone fractures in older women
5. Diabetes Drugs Avandia, Actos Tied to Fractures in Women
6. Fishy Smell May Keep Patients From Diabetes Drug
7. Small Increase in Diabetes Risk Noted in Statin Patients
8. FDA Approved Diabetes Drug Despite Hints at Cancer Risk
9. Remove Diabetes Drug Avandia From Market: FDA Reports
10. Remove Diabetes Drug Avandia From Market: FDA Documents
11. Excessive Weight Gain During Pregnancy Raises Gestational Diabetes Risk
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Diabetes may start in the intestines, research suggests
(Date:12/9/2016)... ... December 09, 2016 , ... Sober College, ... with the grand opening of the Sober College Robert Pfeifer Memorial Learning Center ... December 2-3, and was attended by an overwhelming amount of alumni, family, colleagues ...
(Date:12/9/2016)... , ... December 09, 2016 , ... "I had a ... inventor from Winchester, Va. "I thought that if the nebulizer had a more child-friendly ... than fearing them." , He developed the patent-pending NEBY to avoid the need to ...
(Date:12/8/2016)... , ... December 08, 2016 , ... ... Franchising Company LLC, announced the first national #QuackGivesBack campaign which supported local ... “This was our first franchise-wide Quack Gives Back initiative, and we’re ...
(Date:12/8/2016)... ... December 08, 2016 , ... With the increasing demand for dental implants, the ... (WIYM) campaign to inform dentists and patients about the safety issues related to dental ... market in the U.S. is projected to reach $6.4 billion in 2018 with more ...
(Date:12/8/2016)... ... 2016 , ... Catalent Pharma Solutions, the leading global provider ... products, today announced that it had joined the Pharmaceutical Supply Chain Initiative (PSCI). ... unite pharmaceutical and healthcare companies that share a vision of better, social, environmental ...
Breaking Medicine News(10 mins):
(Date:12/8/2016)... , Dec. 8, 2016  Eli Lilly and ... results of its phase 3 EXPEDITION3 trial at the ... meeting. As previously disclosed, solanezumab did not meet the ... of solanezumab initiated in people with mild dementia due ... regulatory submissions for solanezumab for the treatment of mild ...
(Date:12/8/2016)... de dezembro de 2016  A Mederi Therapeutics Inc . anunciou aprovação ... não cirúrgico para a doença do refluxo gastroesofágico (DRGE). Foto -  ... ... Live Stretta procedure performed and broadcast during the Chinese ... Union Hospital , ...
(Date:12/8/2016)... Pa. , Dec. 8, 2016  Pennsylvania ... Secretary of Drug and Alcohol Programs Gary ... and insomnia medications, known as benzodiazepines, developed with ... "Benzodiazepines are medications that are frequently prescribed ... when they are used with opioid pain medications, ...
Breaking Medicine Technology: