New brain pathway offers hope for treating hypogylcemia

For those with diabetes, managing blood sugar is a balancing act - if blood sugar is too high it raises the risk for nerve damage, blindness, kidney failure, and heart trouble, and if too low it can lead to a seizure or unconsciousness.

Now a team of scientists from the United Kingdom and the University of Michigan Comprehensive Diabetes Center has taken a step forward in understanding how the brain senses low glucose levels and trigger the body's response. The discovery may accelerate work to safely control diabetes.

A novel pathway buried deep within a region of the brain called the parabrachial nucleus produces the brain hormone cholecystokinin (CCK) that acts as a crucial sensor of blood glucose levels. The hormone helps orchestrate responses around the body when levels drop too low, according to the study published in Nature Neuroscience.

"It is remarkable to find that such an incredibly small set of cells in the brain play such an important role in maintaining normal glucose levels," says study author Lora K. Heisler, Chair of Human Nutrition at the Rowett Institute of Nutrition & Health at the University of Aberdeen.

It's known that CCK cells in the brain modify things like appetite and anxiety but they had previously been overlooked in relation to blood sugar levels, authors say.

"The discovery of the important function of this brain hormone raises the possibility of using drugs targeting the CCK system to boost defences against hypoglycaemia, the clinical syndrome that results from low blood sugar," says study author Martin G. Myers, Jr., M.D., Ph.D., the Marilyn H. Vincent Professor in Diabetes Research at the University of Michigan Comprehensive Diabetes Center.

The authors worked with an international team or researchers from the University of Cambridge, University of Edinburgh, University of Chicago on the findings published in the journal Nature Neuroscience.

Heisler says the identification of the role played by CCK could be of particular significance to an estimated 20 percent of those with diabetes who suffer side effects of low blood sugar, called hypoclycemia.

What are symptoms of hypoglycemia and how low is too low?

The normal range of glucose in the bloodstream is from 70 to 100 mg/dL when the individual is fasting (that is not immediately after a meal). The body's biochemical response to hypoglycemia usually starts when sugars are in the high/mid 70's. At this point, the liver releases its stores and the hormones mentioned above start to activate. In many people, this process occurs without any clinical symptoms. The amount of insulin produced also declines in an attempt to prevent a further drop in glucose.

While there is some degree of variability among people, most will usually develop symptoms suggestive of hypoglycemia when blood glucose levels are lower than 50 mg/dL. The first set of symptoms are called adrenergic (or sympathetic) because they relate to the nervous system's response to hypoglycemia. Patients may experience any of the following;