Oral Drugs May Someday Replace Insulin Injections

A drug development team in Japan has isolated a compound from garlic that may be the basis of an oral treatment for diabetes, replacing the daily injection of insulin.

Investigators at the Suzuka University of Medical Science (Japan) worked with a line of mice that was treated with streptozotocin to render them diabetic. Streptozotocin is a naturally occurring chemical that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine for treating certain cancers of the islets of Langerhans and used in medical research to produce an animal model for type 1 diabetes.

The current study was based on previous findings that suggested that vanadium helped to control blood sugar levels in diabetics. The mineral appeared to work by mimicking the effects of insulin or by increasing the body's sensitivity to the hormone. It was proposed that this mechanism could allow diabetics to effectively control their blood sugar while using lower dosages of insulin medication.
In their paper published in the November 19, 2008, online edition of the journal Metallomics the investigators reported on results of treating diabetic mice with a compound (bis(allixinato)oxidovanadium(IV) or VO(alx)2) of vanadium and allixin, a compound isolated from garlic. Garlic is known to lower and maintain stable blood sugar by helping to increase the amount of insulin available in the bloodstream. This action, together with garlic's ability to lower cholesterol and blood pressure, has spurred it use as a dietary supplement for people with diabetes.

In addition to confirming earlier results showing that oral administration of the complex lowered blood glucose levels in mouse models of both types 1 and 2 diabetes, the investigators analyzed the effects of the complex on genes affected by diabetes. Results indicated that treatment of diabetic mice with insulin or the VO(alx)2 complex normalized the gene expression levels of 152 down-regulated and 11 up-regulated genes, and especially the up-regulation of Cyp2E1 and FoxO1 in the muscles of the diabetic mice.

The authors concluded that, "The insulin-mimetic effects of VO(alx)2 in the streptozotocin-induced diabetic mice may be due to the enhancement of protein phosphorylation leading to the activation or inactivation of the transcriptional machinery. Our findings suggest that the insulin-mimetic effects of VO(alx)2 in diabetes may be due to changes in the protein phosphorylations and their gene expression levels.”

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Suzuka University of Medical Science