Currently, type 2 diabetes treatments focus on replacing insulin or making insulin work more effectively (known as improving insulin sensitivity). But, finding a way to block some of the action of glucagon might also help control type 2 diabetes.
The problem is that because glucagon serves a vital function in keeping the brain and body nourished with glucose in times of fasting, scientists can't make a drug that completely suppresses the action of glucagon.
In addition to the brain not getting enough sugar, early research that just partially blocked glucagon caused weight gain, fatty liver deposits and increased cholesterol. Tabas said it's still not entirely clear why partially blocking glucagon caused these effects.
Clearly, a different approach was needed. So, rather than trying to block glucagon, Tabas and his colleagues followed glucagon's pathways.
"Imagine if you have five pathways: A, B, C, D and E. Blocking pathways A and B can stop diabetes. But, if you block C, D, and E, you cause bad effects. So, you have to move further downstream to find the molecules that are responsible for pathways A and B so you can block those without blocking C, D, and E," Tabas explained.
"The more specific you can get, the less likely you'll have adverse effects," he added.
The pathway they found is an enzyme called CaMKII, and Tabas said this particular pathway is also being studied in inflammatory diseases, such as arthritis and asthma, because inhibiting this enzyme seems to lower inflammation as well.
When the researchers blocked CaMKII in obese mice bred to have diabetes, their blood sugar went down, insulin sensitivity improved, cholesterol decreased and fatty liver improved. And, there was no evidence of adverse effects from blocking CaMKII.
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