ARRA IMPACT REPORT:
Diabetes Imaging


Public Health Burden
Diabetes is the seventh leading cause of death in the U.S. Approximately 26 million Americans are estimated to have diabetes and another 79 million Americans to be at increased risk for developing the disease. Diabetes increases cardiovascular disease risk and is the leading cause of kidney failure, lower limb amputations, and adult onset blindness.

Imaging the Pancreatic Beta Cell in Diabetes
The ability to measure mass, function, and inflammation of the insulin-producing pancreatic beta cell would allow researchers and clinicians to monitor the progression and treatment of diabetes and to study the mechanisms of beta cell failure and regeneration. This is a challenging goal for numerous reasons, requiring ingenuity evidenced by these ARRA-supported preliminary and encouraging results:

  • “Pre-targeting” Imaging Strategy: Researchers at the University of Massachusetts Medical School successfully imaged human insulin-producing pancreas cells, called “islets,” that had been transplanted under the skin of mice using a “pre-targeting” strategy. First, the scientists infuse an antibody into the mice that specifically ’tags’ only the human islet cells. After 2 days, excess antibody is excreted through the mouse’s urine, and a radioactive imaging molecule that binds to the antibody was then injected allowing the islets to be visualized. This technique provided specificity and a robust signal for non-invasively imaging human islets in mice.1
  • Novel Imaging Agent: Researchers at the University of California Irvine demonstrated the potential utility of 18F-fallypride as an imaging agent for pancreas islet cells. Fallypride is a novel imaging agent which binds dopamine receptors. These receptors colocalize with the insulin secreting areas in the pancreatic beta cell. The 18F-fallypride-bound receptors were successful in imaging insulin-secreting cells in rats and transplanted human cells in rats.2

Imaging Brown Adipose Tissue
Unlike white adipose tissue that stores fat, brown adipose tissue (BAT) burns fat to dissipate heat, and helps keep babies and small animals warm. The discovery that BAT is present in adult humans and appears metabolically active with exposure to cooler temperatures may represent a novel strategy to stimulate weight loss. Toward that goal, ARRA-supported investigators made advances in the development of tools to image and measure the amount and activity of brown fat:

  • Magnetic Resonance Imaging of Human BAT: Currently, human BAT can only be visualized using invasive radioactive imaging. Scientists at Harvard Medical School demonstrated the feasibility of measuring BAT volume and function in rats using routine magnetic resonance imaging sequences that are available in most clinical scanners. This technique holds significant promise for imaging in humans as it does not use ionizing radiation, is noninvasive, and has minimal risk.3
  • BAT Measurements in Pediatric Population: By examining existing scans of children and adolescents who had undergone imaging for cancer surveillance, the Harvard Medical School researchers analyzed the volume and activity of BAT in a pediatric population. In this study, researchers observed a more than 5-fold higher rate of BAT in children than in adults, with similar percentages in boys and girls. BAT activity increased from childhood into adolescence, when it was detected in almost half of the patients. As in adults, BAT mass is highest in lean children and correlates with muscle mass.4

Brain Imaging in Obesity and Diabetes
Both obesity and diabetes can affect the brain and its function. Neuroimaging allows scientists to investigate the effects of these conditions on the brain. ARRA-funded researchers added exciting results to our understanding of these conditions:

  • Brain Blood Vessel Imaging Changes in Diabetic Individuals: Diabetes alters blood flow regulation in the brain and contributes to cognitive decline in the elderly, but how it does so is not well-defined. By comparing brain magnetic resonance images of people with type 2 diabetes and people without diabetes, researchers at Beth Israel Deaconess Medical Center found that diabetes is associated with shrinkage of the cerebral cortex; narrowing of brain blood vessels; depression; and slower walking speed. They found that adhesion molecules, which are markers of vascular health, were linked to altered reactivity of blood vessels, slower walking, and poorer flexibility in cognitive function.5
  • Walking Abnormalities associated with Reduced Global Grey Matter Volume in Diabetic Individuals: The same group of researchers examined the relationship between diabetes, grey matter volumes, and ability to walk in people with type 2 diabetes and diabetic peripheral neuropathy (DPN), compared to people without DPN and with or without diabetes. They found that in people with DPN, abnormalities in walking were strongly associated with reduced global grey matter volume, especially within regions linked to motor control.6
  • Insulin Signaling and Dopamine Transport Linkage in Diabetes and Obesity: Researchers at Vanderbilt University and the University of Texas Health Science Center produced complementary studies suggesting that the metabolic hormone insulin modulates the neurotransmitter dopamine which work together to control hunger. In one study, they found that feeding rats a high-fat diet impaired insulin signaling in the brain, which reduced dopamine transporter function in the reward circuitry and led to increased caloric intake. This suggests that disruption of brain insulin signaling could increase risk of “food-abuse” disorders.7 In the other study, the researchers found that, in diabetic rats, the effects of the missing insulin in the brain could be “rescued” by increasing dopamine activity using amphetamine therapy. Magnetic resonance imaging was used to monitor function of the dopamine system. These results indicate that insulin disorders, like diabetes, can disrupt dopamine transporter function and suggest that new therapeutic strategies to restore normal dopamine transporter function may help patients with diabetes and obesity.8

Contributing NIH Institutes & Centers

  • National Institute on Aging (NIA)
  • National Institute on Drug Abuse (NIDA)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  1. 1R21DK082894-01A1 - LIU, GUOZHENG - UNIV OF MASSACHUSETTS MED SCH WORCESTER - WORCESTER - MA
    5R21DK082894-02 - LIU, GUOZHENG - UNIV OF MASSACHUSETTS MED SCH WORCESTER - WORCESTER - MA
    5RC1DK087352-02 - MUKHERJEE, JOGESH - UNIVERSITY OF CALIFORNIA IRVINE - IRVINE - CA
    http://www.ncbi.nlm.nih.gov/pubmed/21361360
  2. 1RC1DK087352-01 - MUKHERJEE, JOGESH - UNIVERSITY OF CALIFORNIA IRVINE - IRVINE - CA
    5RC1DK087352-02 - MUKHERJEE, JOGESH - UNIVERSITY OF CALIFORNIA IRVINE - IRVINE - CA
    5RC1DK087352-02 - MUKHERJEE, JOGESH - UNIVERSITY OF CALIFORNIA IRVINE - IRVINE - CA
    http://www.ncbi.nlm.nih.gov/pubmed/21680697
  3. 5RC1DK087317-02 - KAHN, C RONALD - JOSLIN DIABETES CENTER - BOSTON - MA
    5RC1DK087317-02 - KAHN, C RONALD - JOSLIN DIABETES CENTER - BOSTON - MA
    http://www.ncbi.nlm.nih.gov/pubmed/22343821
  4. 1RC1DK087317-01 - KAHN, C RONALD - JOSLIN DIABETES CENTER - BOSTON - MA
    5RC1DK087317-02 - KAHN, C RONALD - JOSLIN DIABETES CENTER - BOSTON - MA
    5RC1DK087317-02 - KAHN, C RONALD - JOSLIN DIABETES CENTER - BOSTON - MA
    http://www.ncbi.nlm.nih.gov/pubmed/21839465
  5. 1R01AG028076-01A2, http://www.ncbi.nlm.nih.gov/pubmed/21926285 - NOVAK, VERA - BETH ISRAEL DEACONESS MEDICAL CENTER - BOSTON - MA
  6. 1R01AG028076-01A2, http://www.ncbi.nlm.nih.gov/pubmed/22665216 - NOVAK, VERA - BETH ISRAEL DEACONESS MEDICAL CENTER - BOSTON - MA
  7. 2R01DA014684-06A2 - GALLI, AURELIO - VANDERBILT UNIVERSITY MED CTR - NASHVILLE - TN
    5R01DA014684-07 - GALLI, AURELIO - VANDERBILT UNIVERSITY MED CTR - NASHVILLE - TN
    5R01DA014684-07 - GALLI, AURELIO - VANDERBILT UNIVERSITY MED CTR - NASHVILLE - TN
    http://www.ncbi.nlm.nih.gov/pubmed/21969871
  8. 2R01DA014684-06A2 - GALLI, AURELIO - VANDERBILT UNIVERSITY MED CTR - NASHVILLE - TN
    5R01DA014684-07 - GALLI, AURELIO - VANDERBILT UNIVERSITY MED CTR - NASHVILLE - TN
    5R01DA014684-07 - GALLI, AURELIO - VANDERBILT UNIVERSITY MED CTR - NASHVILLE - TN
    http://www.ncbi.nlm.nih.gov/pubmed/22357848