Hypoglycemia Associated Autonomic Failure
Many health related problems are associated with hyperglycemia (high blood sugar) such as blindness, kidney failure, and/or cardiovascular disease in diabetic patients. The onset and severity of these chronic complications may be lessened when insulin is taken frequently by diabetics. Unfortunately, more frequent insulin taken may result in more frequent episodes of hypoglycemia (low blood sugar).
The counterregulatory neuroendocrine response to hypoglycemia consists of the elevations of epinephrine, adrenal glucocorticoids, glucagaon, and the activation of the sympathetic nervous system. This response is blunted with multiple bouts of hypoglycemia, a syndrome known as Hypoglycemia Associated Autonomic Failure (HAAF). Little is known about the mechanism(s) incuding HAAF and the brain regions involved. Therefore, the hypotheses presented are: HAAF may result from decreased activation of the brain regions that initiate the counterregulatory response to hypoglycemia. HAAF is mediated by glucocorticoids. This is supported by the fact that HAAF-like effect occurs in humans with moderated, clamped hypoglycemia after previous infusions of cortisol. Cortisol is the predominant adrenal glucocorticoid in humans.
To investigate whether increases of the adrenal glucocorticoid, corticosterone (CORT), is able to induce HAAF-like effects, the lab compared the neuroendocrinei response to hypoglycemia in rats with prior exposure to hypoglycemia or CORT. Also in addition to measuring the neuroendocrine response, immunocytochemical measurements of a protein that is involved in gene translation initiation, cFOS, were used. The protein cFOS is produced in the brain in response to many types of stimuli including laboratory induced hypoglycemia. The results from the cFOS will indicate which regions of the brain are active in regulating hypoglycemia. The lab suggests that the paraventricular nucleus of the hypothalamus will play a major role in responding to hypoglycemia and therefore should have high cFOS activity. Understanding the brain mechanism(s) that reestablish normal blood glucose levels can then be used to help maintain regular responses to drops in blood sugar levels of insulin dependent diabetics.
