BME Research and
Development Programs
Diabetes, Obesity, and Metabolic Diseases
Preventing chronic diseases that happen because of diet, aging, and medications (Drs.
Krishna and Grobmyer)
Various factors – often related to diet, aging, and medications – cause long-term, continual stress on the body. These
environmental and lifestyle factors include inhaling polluted air, drinking alcoholic beverages, taking oral contraceptives, and
becoming overweight/obese. Such chronic stressors can trigger inflammation and disorders such as cancer, inflammatory
bowel disease, or conditions in which nerves and muscles deteriorate. Certain highly reactive species called “free radicals”
(molecules that have unstable electron) are part of this disease-causing process. These free radicals tend to damaging
healthy tissues and organs causing diseases. If we had no stress, our natural antioxidants could get rid of these “free
radicals”; but under stress, the amount of free radicals generated is too high to be handled by our antioxidants. Research has
focused on natural and traditional antioxidant supplements, such as green tea and vitamins. However, these don’t always
work, for following reasons: 1) they may work on only one type of free radical; 2) they may not fight off very high levels of free
radicals; 3) they may not be in a form that the body can use most effectively; 4) not all traditional antioxidants activate body’s
own natural antioxidant system; and 5) certain traditional antioxidants may themselves generate free radicals. Using
nanoengineering materials (NEMs), we are designing unique tiny structures that overcome these drawbacks by working on
many types and even on high levels of free radicals, but being easily processed by the body to be really effective. Our early
studies have shown that these new NEM-antioxidants are safe, nontoxic and do not generate free radicals. Our NEMs
formulation could be made to be taken either by mouth or just rubbed onto the skin. At this point, philanthropic money could
help us move our NEMs-antioxidant research forward more rapidly.
Summary: Dr. Krishna and Dr. Grobmyer are developing new nanotechnology for unique antioxidants that are safe to use
and that can prevent certain diseases caused by environmental and lifestyle factors that cause us harm.
Healing of Diabetic Skin Wounds (Dr. Maytin)
Delayed wound healing can be a serious, even life-threatening problem, especially in people with obesity and adult-onset
diabetes. Today, over 6 million Americans have chronic, nonhealing ulcers on the feet or legs – large wounds that may not
heal for months or years. About 100,000 people per year undergo amputation for such ulcers. Even in the 21st century, the
available creams and wound dressings may still fail to improve wound healing, which only shows how little we still know about
how healing works. In the Maytin laboratory, we are asking how hyaluronan (HA), a molecule composed entirely of sugars,
helps to regulate wound healing. In diabetics, high blood sugar levels seem to slow or prevent healing, but how this happens
is not well understood. In the skin, the amount and size of HA (which is affected by sugar availability) is likely to be a major
contributor to abnormal inflammation, build-up of fibrous tissue (as in scarring), and delayed healing under high-sugar
conditions.
Summary: By studying how HA controls wound healing, we believe our line of research will ultimately lead to new therapy
that can speed healing, especially for people with obesity and diabetes.
Diabetes and Obesity: A Possible Cause and Eventual Cure? (Dr. Hascall)
To discover how cells are affected by diabetic conditions, we study “stem cells,” which exist in the adult body and can become
any of a number of more highly specialized cell types. Our research uses adult stem cells from bone marrow.
Under normal conditions, stem cells divide into one bone-forming cell and one stem cell. We have shown that in the presence
of abnormally high blood sugar, they instead divide into two fat cells. As a reaction to being in the high-glucose solution, these
fat cells synthesize a supporting structure (the “extracellular matrix”) made up of the molecule hyaluronan (HA). The presence
of this material causes inflammation and can reduce the animal’s bone mass. The abnormal multiplication of fat cells in the
presence of high sugar could be a major cause for the ongoing epidemic of obesity in our society and might also be relevant
to bone loss or osteoporosis.
Summary: Dr. Hascall's laboratory investigates a possible reason for the abnormal cell division that causes the formation of
fat cells and structures involved in obesity and diabetes in humans. This research may lead to the development of drugs and
therapies to prevent the development of obesity.