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UT graduate students win research grants |
| By
Jim Winkler |
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Jan 7, 2008 |
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Two graduate students studying in the Center for Diabetes and Endocrine Research (CeDER) on the Health Science Campus have received grants from the American Heart Association (AHA) and the American Diabetes Association (ADA).
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| Garrett Heinrich, left, and Jehnan Liu review the results of an experiment. |
Garrett Heinrich, a PhD student, is recipient of a two-year, $40,000 AHA award for a study titled “A Novel Molecular Link Between Vascular and Metabolic Diseases,” while Jehnan Liu, an MD/PhD student, has received a three-year, $90,000 ADA Physician Scientist Training Award for a study titled “CEACAM2: A Novel Mechanism of Diabetes and Complications.”
The CeDER is headed by Dr. Sonia Najjar, professor of physiology, pharmacology, metabolism and cardiovascular sciences, who has done pioneering work on the discovery of the role of a protein called CEACAM1 as a cause of obesity, fatty liver disease and type 2 diabetes and on the genetic and dietary basis of the diseases. Her laboratory also is investigating the molecular basis of the increase in the rate of death of common types of cancer with increased obesity.
Using genetically modified mice, Najjar and her research team have found when the body has difficulty in clearing insulin, obesity increases and insulin resistance develops, resulting in type 2 diabetes. Najjar’s discovery, coupled with the identification of CEACAM1, a liver protein that controls insulin clearance, could play a major role in finding a cure for type 2 diabetes.
The laboratory has developed genetically altered mice, which express an inactive form of CEACAM1 in the liver. The mice — called L-SACC1 — develop obesity and insulin resistance.
Heinrich is investigating whether the mouse model develops atherosclerosis, which can lead to impairments in blood flow, blood clotting and stroke.
Feeding the mice a diet high in fat makes them diabetic and causes fat deposits and inflammation in the liver similar to that seen in human patients with non-alcoholic steatohepatitis, a disease on the rise in the United States along with obesity.
“It is expected that more people will develop the disease,” Heinrich said. “We plan to use the L-SACC1 mouse on a high-fat diet to determine if these characteristics occur not only in the liver, but also in blood vessels, as in atherosclerosis.
“If the L-SACC1 mice on a high-fat diet develop atherosclerotic lesions,” he continued, “we would be able to introduce hepatic CEACAM1 as a therapeutic target in the treatment of vascular dysfunction in obesity and type 2 diabetes. Developing a drug that increases the level and/or activity of CEACAM1 in the liver would be important research for the future.”
A 2001 bioengineering graduate of the University of California at Berkeley, Liu is investigating the role of CEACAM2, which is produced in the brain cells controlling food intake, in insulin action and energy balance.
Preliminary laboratory work reveals that female mice with genetic deletion of CEACAM2 develop insulin resistance due to decreased energy expenditure in muscle and increased food intake. Male mice develop the same problem, but at a much older age.
“However in males and females,” Liu noted, “the secretion of insulin in response to glucose was decreased with age and the presentation of the disease simulates the situation in uncontrolled older human type 2 diabetics who exhibit decreased ability of the pancreas to secrete insulin to compensate for insulin resistance in muscle.”
To identify a role for CEACAM2 in insulin secretion and in regulating food intake and energy balance, he plans to feed the genetically altered CEACAM2 mice a high-fat diet to decrease CEACAM1 levels in the liver.
“In this manner, we would be able to understand how insulin secretion from pancreatic cells and insulin clearance in liver interact to regulate insulin action,” Liu explained.
“This will place CEACAM2 at the intersection of altered insulin secretion and peripheral insulin resistance,” Liu added, “and promote CEACAM proteins as therapeutic targets for complex diseases such as type 2 diabetes.”
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