Sodium salicylate, a cousin to aspirin, reduced blood sugar levels in obese people and patients with Type 2 diabetes in recent studies, and a new study in mice finds a key way the drug does so. The results will be presented Tuesday at The Endocrine Society’s 92nd Annual Meeting in San Diego.
“Obesity is now viewed as a condition where the fat tissue in the body becomes inflamed. However, it was not clear how anti-inflammatory drugs like aspirin lower blood sugar levels and improve insulin sensitivity in obese mice and patients,” said study co-author Brian Walker, MD, PhD, professor of endocrinology at the University of Edinburgh in the U.K.
“We found that the ability of these drugs to prevent complications of obesity depends on lowering ‘stress’ steroid hormone levels in fat,” he said.
These hormones, called glucocorticoids, likely increase because of the inflammation in fat and then lead to the detrimental effects on metabolism seen in obese people, such as Type 2 diabetes, Walker believes.
He and his group investigated whether sodium salicylate or salsalate (a prodrug of sodium salicylate) could reduce production of glucocorticoids in fat. They treated obese mice for four weeks either with sodium salicylate, using a minipump that delivered the drug below the skin, or with a solution that did not contain this drug (vehicle).
Sodium salicylate treatment improved blood glucose (sugar) levels and insulin resistance, the investigators found. Treatment also reduced amounts of an enzyme called 11-beta-hydroxysteroid dehydrogenase 1 (11-beta-HSD1), which generates glucocorticoids in fat, particularly in belly fat. Knockout mice that genetically lack this enzyme were resistant to the effects of sodium salicylate. Walker said these findings demonstrate that 11-beta-HSD1 probably is a key mechanism behind the glucose-lowering ability of salicylates.
“We have evidence that the same changes to 11-beta-HSD1 occur in humans after salsalate treatment. Inhibiting 11-beta-HSD1 in fat may be a useful treatment strategy in obesity,” Walker said.
Possibly, even nonsalicylate drugs that inhibit 11-beta-HSD1 would prevent the cardiovascular complications of obesity, he added. A recent study by other researchers found that an experimental 11-beta-HSD1 inhibitor that is not a salicylate improved blood sugar and cholesterol levels in patients with Type 2 diabetes.
Funding sources for Walker’s study included the British Heart Foundation, the Wellcome Trust and the Medical Research Council in the U.K.
