Alberta Innovates- Health Solutions

Insulin resistance link
Heritage researcher Dr. David Brindley is working out the signalling pathways for a lipid messenger in fat cells, called ceramide, which has different effects on different types of cells. It can cause white blood cells to die, or fibroblasts to divide and produce scar tissue. In fat tissue, the ceramide pathway prevents the uptake and use of insulin-stimulated glucose by cells. However, without insulin, fat cells still can take up glucose through another mechanism controlled by ceramide. "Insulin resistance is associated with obesity, and fat cells need glucose to grow in the absence of effective insulin action. This ceramide mechanism bypasses insulin and can contribute to fat growth in people who are insulin-resistant, says Dr. Brindley. His research could bring new insights into insulin resistance, a major health problem for nine out of ten type II diabetics in the developed world.

Links to cancer and atherosclerosis
The proteins produced by genes dictate the functions of all living organisms. To control what the proteins do, cells attach different types of molecules, such lipids, to the proteins like chemical "postal codes." Heritage researcher Dr. Luc Berthiaume studies how these combinations of different fats and proteins cause cancer. He's testing compounds that prevent this modification. Two of his compounds have shown to be very promising and might lead to a new type of anti-cancer drug. He's also studying apolipoprotein B (apo B), a protein that is changed by a fat called palmitate. Apo B helps transport cholesterol and triglycerides in the blood, a function controlled by palmitate. Understanding how palmitate works could help people who have too much cholesterol and triglycerides in their bloodstreams, a risk factor for heart attack and stroke.

One of these proteins, called apolipoprotein E (apo E), has been linked to Alzheimer's disease, because of a single substitution at one of two positions in the protein's chain of 299 amino acids. Of the three common forms apo E can take in humans, one is often found in people who suffer Alzheimer's disease. Another form of apo E however, differing by only one amino acid, is thought to protect against the disease.

Heritage researcher Dr. Robert Ryan is studying the way apo E interacts with lipoproteins particles and a cell membrane receptor to determine how it might be involved in heart disease and Alzheimer's disease. Dr. Jean Vance uses three models to study the ways lipids are moved around in cells to build cell membranes. She is also looking at the role of lipids in the growth and development of nerve cells, particularly apo E, implicated in Alzheimer's disease. Dr. Richard Lehner is studying three enzymes that are involved in how a fat called triacylglycerol (TG) is used in the body. Too much TG leads to obesity. He has found an inhibitor to one of these enzymes that has potential as a lipid lowering drug.

All five scientists are funded by the Medical Research Council of Canada and four are funded by the Heart and Stroke Foundation of Alberta and the Northwest Territories.

Dr. David Brindley is a Heritage Medical Scientist at the U of A. He also receives support from the National Institutes of Health (USA) and the Canadian Diabetes Association.

Dr. Luc Berthiaume is a Heritage Scholar.

Dr. Robert Ryan is a Heritage Medical Scientist. He has three AHFMR-funded trainees working in his lab: Dr. Paul Weers and Dr. Vincent Raussens, both postdoctoral fellows; and Ms. Daisey Sahoo, a student.

Dr. Richard Lehner was an AHFMR postdoctoral fellow who is now on faculty at the U of A. He is funded by a MRC-Pharmaceutical Manufacturers Association of Canada, a Canadian Lipoprotein Conference/Parke-Davis/Pfizer research grant and by Glaxo-Wellcome.

Dr. Jean Vance is also funded by the Alberta Paraplegic/Rick Hansen Foundation.