Gene analysis identifies potential metformin alternative
medwireNews: Analysis of gene expression changes underlying excess glucose production in the liver has identified a drug – derived from broccoli – with a mechanism of action complementary to that of metformin.
In cultured liver cells, the drug, sulforaphane, reduced glucose production by downregulating key enzymes involved in gluconeogenesis, meaning its mode of action was different to that of metformin, which acts by lowering cyclic AMP and inhibiting mitochondrial glycerophosphate dehydrogenase.
As reported in Science Translational Medicine, the researchers identified the compound from among 3852 “drug signatures” (ie, the changes in gene expression caused by the drugs). These were compared against 50 hepatic genes most likely to have a role in diabetes pathophysiology, identified in turn from an initial set of 1720 genes involved in glucose production in the liver.
Having established the ability of sulforaphane to improve glucose tolerance in animal models, Anders Rosengren (Lund University Diabetes Center, Malmö, Sweden) and co-researchers randomly assigned 103 patients with type 2 diabetes to receive sulforaphane 150 μmol once daily in the form of an aqueous extract of broccoli sprouts, or placebo. Most patients were also taking metformin.
Among the 97 patients who completed the study, taking sulforaphane for 12 weeks resulted in significant reductions in fasting blood glucose and glycated hemoglobin specifically in patients who had poorly controlled diabetes, were obese, or had elevated triglyceride levels. Its effectiveness was also greater in patients who were more insulin resistant or had elevated liver fat.
The team cautions that sulforaphane cannot yet be recommended as an antidiabetic treatment, but notes that besides the glucose-lowering effect shown in the current study, the drug also has antioxidant effects that protect against diabetic complications such as neuropathy and renal failure in animal models.
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