Understanding How the Body Senses Low Blood Sugar Levels

One of the more challenging problems in diabetes is hypoglycemia unawareness. Normally, a person will feel warning symptoms when their blood sugar goes low, such as shaking and sweating caused by release of stress hormones. However, those with hypoglycemia unawareness have reduced warning signals and do not recognize they are low. The individual can lose consciousness, and blood glucose levels continue to fall until external assistance is provided. This research is designed to better understand how the brain senses changes in blood glucose to ultimately develop therapeutic approaches to prevent or treat hypoglycemia unawareness. A key focus is studying how the brain responds to blood glucose challenges to promote release of these ‘warning’ stress hormones. Some stress hormones are primarily reactive such as the release of epinephrine whereas others such as glucocorticoids and growth hormones are more adaptive than reactive because they provide ability to modify metabolic processes over longer periods of time. These investigators found a novel signal transfer mechanism, controlled by a kinase pathway, in corticotropin-releasing (CRH) neurons in the brain’s hypothalamus that transduces incoming information on blood glucose challenges into downstream secretion of the glucocorticoid hormones.

Ramifications for Individuals with Type 1 Diabetes:

This work attempts to understand the mechanisms that may be impaired during insulin-induced hypoglycemia in T1D which underlie hypoglycemia unawareness. This knowledge will help address the problem of normal glucose maintenance and regulation in T1D. The ultimate goal is for this work is to prevent or treat hypoglycemia unawareness and contribute towards better ways for individuals with T1D to manage their treatment regimes. These strategies could include drug and/or device-based approaches such as the artificial pancreas.

Reference:

Arshad M., Kaminski, KL., Sanchez-Watts, G., Ponzio, TA., Kuzmiski, JB., Bains, JS., and Watts, AG. (2011). MAP Kinases Couple Hindbrain-Derived Catecholamine Signals to Hypothalamic Adrenocortical Control Mechanisms during Glycemia-Related Challenges. The Journal of Neuroscience, 14 December, 31(50): 18479-18491.

JDRF Involvement:

JDRF funded this work via a grant to Alan Watts at the University of Southern California.