Could the antidote to cyanide treat diabetes?

John Murphy, MDLinx | June 13, 2016

Researchers have shown that a cyanide antidote boosts the activity of a “lean gene” to treat type 2 diabetes, according to a study published online June 6, 2016 in the journal Nature Medicine.

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Cyanide linked to diabetes treatment

An investigation of obese mice and lean mice (such as these from a separate study) showed that a cyanide antidote markedly improved diabetes in the obese mice.

In this study, scientists investigated genetic differences between lean but healthy mice and obese mice. The researchers found that the healthy mice had a ‘lean gene’—Tst—that resists metabolic disease, such as obesity and diabetes.

When the researchers boosted levels of the enzyme thiosulfate sulfurtransferase (or TST, which has been used for decades as an antidote to cyanide), the obese mice showed drastic improvements in diabetes.

But the discovery isn’t strictly limited to mice—the research could be translated to clinical trials in humans too, the researchers suggested.

“Gaining this unique insight into the genes of healthy leanness could lead to a completely new approach to treating diabetes associated with obesity,” said one of the study’s lead researchers Nik Morton, PhD, Chair of Molecular Metabolism at the University of Edinburgh’s Centre for Cardiovascular Sciences, in Edinburgh, UK.

The finding is a result of a new take on studying genetics for obesity, the researchers pointed out. Instead of looking for genes that cause obesity, this investigation sought to find genes that prevent people from becoming obese.

“By focusing on obesity resistance rather than susceptibility, we have identified a more common genetic trait linked to leanness. Our findings highlight the importance of the fat tissue in peripheral control of body weight and metabolism,” said the study’s other leader Simon Horvat, PhD, Professor in the Department of Genetics and Immunology at the University of Ljubljana, in Ljubljana, Slovenia.

The researchers’ impetus for the study was their finding that lean mice fed a high-fat diet still lost weight that couldn’t be entirely explained by eating patterns or additional exercise—something else must be going on. Perhaps there was a genetic reason—a gene for leanness—that prevented lean mice from becoming obese, they reasoned.

The investigators also found that fat mice fed a high-fat diet both gained weight and showed lower levels of adipose TST. Upon investigating, they discovered that lean mice had, by contrast, higher levels of TST.

Given this finding, the investigators tested whether increasing TST in fat diabetic mice could offer a beneficial effect. They found that boosting TST levels markedly ameliorated polydipsia, polyuria, insulin-resistance, and elevated HbA1c levels in the diabetic mice, although it did not lessen body weight or fat mass.

TST, also called rhodanese, was discovered more than 80 years ago as part of the body’s protection against cyanide poisoning.

The TST treatment now shows promise as a novel therapy for diabetes in humans, but first it needs to be further developed to improve specificity and efficacy, the researchers noted.

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