New research suggests that obesity and diabetes are a downside of human evolution

Feb 24, 2011

As if the recent prediction that half of all Americans will have diabetes or pre-diabetes by the year 2020 isn't alarming enough, a new genetic discovery published online in the FASEB Journal (http://www.fasebj.org) provides a disturbing explanation as to why: we took an evolutionary "wrong turn." In the research report, scientists show that human evolution leading to the loss of function in a gene called "CMAH" may make humans more prone to obesity and diabetes than other mammals.

" is estimated to affect over 25 million individuals in the U.S., and 285 million people worldwide," said Jane J. Kim, M.D., a researcher involved in the work from the Department of Pediatrics at the University of California, San Diego in La Jolla, CA. "Our study for the first time links human-specific sialic acid changes to insulin and and therefore opens up a new perspective in understanding the causes of diabetes."

In this study, which is the first to examine the effect of a human-specific CMAH genetic mutation in obesity-related metabolism and diabetes, Kim and colleagues show that the loss of CMAH's function contributes to the failure of the insulin-producing in overweight humans, which is known to be a key factor in the development of . This gene encodes for an enzyme present in all mammalian species except for humans and adds a single oxygen atom to sialic acids, which are sugars that coat the cell surface.

To make their discovery, the researchers used two groups of mice. The first group had the same mutant CMAH gene found in humans. These mice demonstrated that the CMAH enzyme was inactive and could not produce a sialic acid type called NeuSGc at the . The second group had a normal CMAH gene. When exposed to a high fat diet, both sets of mice developed as a result of their obesity. Pancreatic beta cell failure, however, occurred only in the CMAH mutant mice that lacked NeuSGc, resulting in a decreased insulin production, which then further impaired blood glucose level control. This discovery may enhance scientific understanding of why humans may be particularly prone to develop type 2 diabetes. Results may also suggest that conventional animal models may not accurately mirror the human situation.

"The diabetes discovery is an important advance in its own right. It tells us a lot about what goes wrong in diabetes, and where to aim with new treatments," said Gerald Weissmann, M.D., Editor-in-Chief of the , "but its implications for are even greater. If this enzyme is unique to humans, it must also have given us a survival advantage over earlier species. Now the challenge is to find the function of CMAH in defending us against microbes or environmental stress or both. This evolutionary science explains how we can win some and lose some, to keep our species ahead of the extinction curve."

Explore further: Researcher develops, proves effectiveness of new drug for spinal muscular atrophy

More information: Sarah Kavaler, Hidetaka Morinaga, Alice Jih, WuQiang Fan, Maria Hedlund, Ajit Varki, and Jane J. Kim. Pancreatic β-cell failure in obese mice with human-like CMP-Neu5Ac hydroxylase deficiency. FASEB J. fj.10-175281; doi:10.1096/fj.10-175281

add to favorites email to friend print save as pdf

Related Stories

Fat cells send message that aids insulin secretion

Nov 06, 2007

The body's fat cells help the pancreas do its job of secreting insulin, according to research at Washington University School of Medicine in St. Louis. This previously unrecognized process ultimately could lead to new methods ...

Apelin hormone injections powerfully lower blood sugar

Nov 04, 2008

By injecting a hormone produced by fat and other tissues into mice, researchers report in the November Cell Metabolism that they significantly lowered blood sugar levels in normal and obese mice. The findings suggest that t ...

Body's anticipation of a meal can be a diabetes risk factor

Mar 11, 2010

Alterations in our response to the taste or smell of food may be another culprit responsible for Type 2 diabetes, according to scientists at Duke University Medical Center who have identified the specific mechanism in human ...

Recommended for you

Cellular protein may be key to longevity

Sep 15, 2014

Researchers have found that levels of a regulatory protein called ATF4, and the corresponding levels of the molecules whose expression it controls, are elevated in the livers of mice exposed to multiple interventions ...

Gut bacteria tire out T cells

Sep 15, 2014

Leaky intestines may cripple bacteria-fighting immune cells in patients with a rare hereditary disease, according to a study by researchers in Lausanne, Switzerland. The study, published in The Journal of Experimental Me ...

T-bet tackles hepatitis

Sep 15, 2014

A single protein may tip the balance between ridding the body of a dangerous virus and enduring life-long chronic infection, according to a report appearing in The Journal of Experimental Medicine.

User comments : 0