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July 17, 2014
Reversal of Type II Diabetes May Be Possible
Here's some big news: Ron Evans and co-workers at Salk report that treatment with the growth factor FGF1 appears to reverse type II diabetes in mice. (Article in Science Daily on this study here). Evans has been working in this field (diabetes, insulin sensitivity, and related areas like growth factors and nuclear receptors) for a long time, and I would definitely take this work seriously.
They reported a couple of years ago that FGF1 seemed to be involved in insulin sensitivity. It's induced in adipose tissue under high-fat diet conditions. FGF1 knockout mice, for their part, have a seemingly normal phenotype, but when they're put on high-fat diets they respond very poorly indeed, quickly showing abnormal glucose control and other defects.
This new paper shows that in normal mice with metabolic problems brought on by a high-fat diet, a single injection of recombinant FGF1 is sufficient to normalize glucose for up to 48 hours. Interestingly (and importantly), this mechanism doesn't seem to overshoot - you don't swing over to hypoglycemia, which is always a worry in this field. And repeated FGF1 therapy leads to increased insulin sensitivity, suppression of hepatic glucose production - basically, everything you'd want in a Type II diabetes therapy. It's great stuff, and the best candidate I've yet seen for the Real Mechanism behind the disease.
Now, FGF1 is a cellular growth factor, so there's a possibility for trouble. But the glucose/insulin effects seem to be mediated by one particular FGF receptor (FGFR1), which makes one hopeful that this axis can be separated out. I would expect to see a great deal of work coming on variants of the protein with longer plasma half-life and greater selectivity. In vivo, the protein seems to be secreted and used locally in specific tissues - it's not in wide circulation. But perhaps it should be - you can be sure that someone's going to try to find out. Overall, this is excellent, exciting news, and we're poised to learn a huge amount about type II diabetes and how to treat it.
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