Australian scientists, in association with US pharmaceutical company DiaKine Therapeutics, have shown that a drug candidate, Lisofylline, could be useful in treating Type 2 diabetes.
Drs Georgia Frangioudakis and Carsten Schmitz-Peiffer from Sydney's Garvan Institute of Medical Research, tested the anti-inflammatory drug which is undergoing clinical trials for other diseases, on mice being fed high-fat diets. Their findings are published in the journal Endocrinology, now online.
"This is the first time it has been suggested that Lisofylline could be useful in treating Type 2 diabetes," said Dr Schmitz-Peiffer. "We believe it works by preventing the build up of certain by-products of fat metabolism."
"Fats build up in the muscle and liver cells of obese people or high-fat fed mice. When those fats are metabolised, their breakdown products prevent the normal movement of glucose into cells."
The hormone insulin is produced after we eat to move glucose from our bloodstream into our cells for energy. When people get fat, that process becomes compromised and they develop 'glucose intolerance', or 'insulin resistance', precursors of Type 2 diabetes.
"The blood sugar levels of people with insulin resistance take a long time to come down after eating because glucose can't get into their cells," explained Schmitz-Peiffer. "High blood sugar can lead to many unwelcome complications, such as kidney failure and blindness. So it's something you want to control if you possibly can."
"Certain drugs can prevent the various metabolites of fat from accumulating, and we were interested in blocking development of one known as 'Ceramide'."
"A lot of studies have shown that a build up of Ceramide in muscle correlates at least with a build up of insulin resistance."
"In the absence of Ceramide, the transmission of signals between molecules inside cells improves, and so does the ability of insulin to be effective."
"As it happens, Lisofylline is effective in preventing the build up of a number of fat metabolites, including Ceramide. While we don't yet understand all the mechanisms, we believe the blocking of Ceramide may have something to do with the drug's anti-inflammatory properties."
"We tested Lisofylline and another fat metabolism inhibitor under different dietary conditions, and Lisofylline was able to improve insulin action under all of them, making it a useful potential treatment for obesity-related insulin resistance."
"Lisofylline has already undergone Phase 1 clinical trials, and has been shown to be safe when used in healthy subjects. It is undergoing Phase 2 clinical trials for other purposes at the moment."
"These new results suggest that the development of Lisofylline, or other drugs that might be orally bioavailable with the same spectrum of activity, may be a novel approach to the treatment for Type 2 diabetes."
- G. Frangioudakis, J. Garrard, K. Raddatz, J. L. Nadler, T. W. Mitchell, C. Schmitz-Peiffer. Saturated- and n-6 Polyunsaturated-Fat Diets Each Induce Ceramide Accumulation in Mouse Skeletal Muscle: Reversal and Improvement of Glucose Tolerance by Lipid Metabolism Inhibitors. Endocrinology, 2010; 151 (9): 4187 DOI: 10.1210/en.2010-0250
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