A PIONEERING hormone treatment may be the secret to an easy life for diabetics, consigning insulin shots and regular glucose monitoring to the medical history books.
Most people associate diabetes with insulin, the pancreatic hormone that dictates how much glucose circulates in blood. Type 1 diabetics have to inject the hormone because they can鈥檛 make it themselves. Now, the spotlight is turning on insulin鈥檚 lesser-known pancreatic twin, glucagon, as a treatment that could control blood glucose levels without the need for daily monitoring.
Whereas insulin clears surplus glucose from the blood after meals, squirrelling it away in the liver, muscles and elsewhere, glucagon does the opposite when we are hungry, ordering the liver to release stores of glucose 鈥渇uel鈥� into the blood or to make more if none is available.
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To investigate glucagon鈥檚 role, at the University of Texas Southwestern Medical Center in Dallas and colleagues engineered mice to lack glucagon receptors so they couldn鈥檛 respond to the hormone. Surprisingly, the mice had normal levels of blood glucose. Then, when the team used a toxin to destroy the pancreatic beta cells that make insulin, the mice remained diabetes-free.
鈥淭he bottom line is that without glucagon, you can鈥檛 get diabetes,鈥� says Unger. Even more mystifying, when the mice consumed huge amounts of sugar in so-called 鈥済lucose tolerance鈥� tests, their blood glucose levels remained normal, irrespective of whether or not they could make insulin ().
鈥淭he implication for humans is that [without glucagon] you could drink 10 bottles of sugary drinks and your blood sugar would remain the same, with or without insulin,鈥� he says. 鈥淭his was a huge surprise.鈥�
So theoretically, if glucagon could be safely neutralised in people with type 1 diabetes, their blood glucose levels would stay normal without them having to take insulin or constantly check that level. 鈥淭he only potential downside is too little glucose in the blood, or hypoglycaemia,鈥� says Unger. But this would only likely become an issue if a person was due to run a marathon, or do something equally energy-sapping. 鈥淭he answer would be to take a sugary drink with you,鈥� he says.
The results in mice are so encouraging that a trial has already begun to see if suppressing glucagon has similar benefits in people with diabetes. of San Diego, California, is attempting to do this with leptin, a hormone that controls fat uptake by cells but which also dampened the action of glucagon in studies on mice by Unger鈥檚 team in 2008.
鈥淚t鈥檚 the first time that researchers will test leptin, in the form of an analogue called metreleptin, in people with type 1 diabetes to see if it can improve glucose control,鈥� a company spokeswoman told 快猫短视频. The volunteers will not go without insulin, but will receive the minimum safe amount.
Other diabetes researchers are encouraged, but cautious about the developments. 鈥淚f you get rid of the glucagon receptor, you get these dramatic changes,鈥� says Alan Cherrington of Vanderbilt University School of Medicine in Nashville, Tennessee. 鈥淏ut is it more relevant in rodents than in humans?鈥� he asks.
Cherrington says that the study leaves important questions unanswered. Firstly, where does surplus glucose go in the mice lacking glucagon and insulin? Unger agrees that this urgently needs investigation and says that tracer studies are under way with labelled glucose so its fate in the animals can be tracked. The most likely destination, according to Cherrington, is the liver, but if so, what happens when it is 鈥渇ull up鈥�?
The key question is: how are the mice managing to regulate glucose if insulin is not involved? Cherrington鈥檚 hunch is that glucagon-like peptide-1 (GLP-1), a hormone made in the gut, may be deputising. 鈥淕LP-1 may affect the liver and muscle in an insulin-like way, ordering them to store glucose,鈥� he says.
at the Samuel Lunenfeld Research Institute in Toronto, Canada, who investigates GLP-1 and glucagon, agrees. 鈥淎nimal models show elimination of glucagon is associated with increased circulation of GLP-1, so this hormone may certainly be playing a role,鈥� he says.
Drucker also says that suppressing glucagon levels, as expected in the leptin treatment, is probably safer than completely blocking the receptors. That鈥檚 because blocking causes the cells that make glucagon to multiply rapidly to increase glucagon output, potentially resulting in the development of a pancreatic tumour. This shouldn鈥檛 happen if glucagon action is only dampened.
Another question, of course, is how the finding will translate to people with type 1 diabetes, says Robert Henry of the University of California at San Diego, who is head of medicine and science for the . 鈥淭he animals don鈥檛 have any glucagon activity from birth, so would blocking the hormone have different effects in animals or humans already producing it?鈥� he says.
Although cautious, most commentators were confident that the finding could lead to new treatments, or at the very least to new insights challenging the historical pre-eminence of insulin. 鈥淚t raises a large number of issues challenging the classic dogma that insulin is the most important hormone in diabetic control,鈥� says Henry.
