New antidote to diabetic arsenic victims
doi:10.1038/nindia.2013.31 Published online 4 March 2013
Arsenic destroys insulin molecules. So what happens to diabetics living in areas with arsenic contamination of ground water? They suffer a double whammy: one, of arsenic poisoning and two, of unsuccessful diabetes treatment. Insulin treatment has had limited success among such people since arsenic disrupts the therapeutic process.
Researchers from University of Kalyani in West Bengal now bring new hope. They have overcome this long-standing problem by wrapping insulin in a coat of polymer nanoparticles to protect insulin from the effect of arsenic. They have successfully used the nanotherapy to alleviate symptoms of arsenic-induced diabetes in mice.
They call the coated product nano-insulin.
"Nano-insulin successfully combats arsenic-induced diabetes at a dose ten times lower than that of normal insulin in mice," said lead researcher Anisur Rahman Khuda-Bukhsh from the Department of Zoology at University of Kalyani. This raises the possibility of using nano-insulin as anti-diabetic therapy in arsenic victims, he told Nature India.
For poverty-stricken arsenic victims, insulin treatment is expensive. In addition, constant arsenic exposure through drinking water destroys the insulin molecule before it can yield any therapeutic benefits. In recent years, nanoparticles have emerged as excellent drug carriers that could deliver insulin in a protective coat. However, no previous studies have investigated the insulin-ferrying potential of such nanoparticles.
In the hope of finding a nanoparticles-based insulin delivery technique, Khuda-Bukhsh and colleagues encapsulated dried insulin particles with poly (lactic-co-glycolic) acid (PLGA), a type of non-toxic and biodegradable polymer nanoparticles. They then injected arsenic-exposed diabetic mice with nano-insulin. For comparison they used similar untreated mice and mice treated with normal non-coated insulin.
The study revealed that nano-insulin had greater efficacy in modulating diabetes-related physiological anomalies such as higher blood glucose, cholesterol and triglyceride levels than non-coated insulin. Nano-insulin did not enter the beta cells in pancreas that secrete insulin. Instead, the polymer nanoparticles were degraded and only the insulin part entered the beta cells triggering a cascade of signaling events leading to secretion of insulin from beta cells.
At low dose, nano-insulin appeared in various cell tissues. At higher dose, nano-insulin was found in the mice brain tissue. "This clearly suggests that nano-insulin has the ability to cross the blood-brain-barrier (BBB)," Khuda-Bukhsh said.
Hypothalamus, a region in brain, acts as glucose sensor. The BBB also participates in brain-sensing of blood glucose levels. Under normal conditions, glucose is the major metabolic fuel that powers brain cells, which constantly need insulin-mediated glucose supply. "This is why the ability of nano-insulin to cross BBB has great implications," added Khuda-Bukhsh.
Nano-insulin is also thermally stable, according to Kiran Kalia of Sardar Patel University, Gujarat, who studies arsenic-induced diabetes and associated disorders. "However, it remains to be seen whether the nano-insulin could work under the oxidative stress generated by arsenic," Kalia pointed out.
Researchers feel the safety of nano-insulin is yet to be validated. "These results are encouraging but more studies are needed before we can try it in humans," says endocrinologist Deep Dutta from the Institute of Post Graduate Medical Education and Research in Kolkata.