Simultaneously, there is measurable alpha cell hypertrophy and hyperplasia in the early stage of the disease, leading to expanded alpha cell mass. This, together with failing beta cell insulin secretion, begins to account for rising glucagon levels that contribute to hyperglycemia. Some researchers believe glucagon dysregulation to be the primary cause of early stage hyperglycemia. Leading hypotheses for the cause of postprandial hyperglucagonemia suggest that exogenous insulin therapy is inadequate to replace the lost intraislet signalling to alpha cells previously mediated by beta cell-derived pulsatile insulin secretion. Under this working hypothesis intensive insulin therapy has attempted to mimic natural insulin secretion profiles in exogenous insulin infusion therapies. Hypoglycemic glucagon impairment
Glucagon secretion is normally increased upon falling glucose levels, but normal glucagon response to hypoglycemia is blunted in type 1 diabetics. Beta cell glucose sensing and subsequent suppression of administered insulin secretion is absent, leading to islet hyperinsulinemia which inhibits glucagon release.Autonomic inputs to alpha cells are much more important for glucagon stimulation in the moderate to severe ranges of hypoglycemia, yet the autonomic response is blunted in a number of ways. Recurrent hypoglycemia leads to metabolic adjustments in the glucose sensing areas of the brain, shifting the threshold for counter regulatory activation of the sympathetic nervous system to lower glucose concentration. This is known as hypoglycemic unawareness. Subsequent hypoglycemia is met with impairment in sending of counter regulatory signals to the islets and adrenal cortex.
Chlorzoxazone (INN) is a centrally acting muscle relaxant used to treat muscle spasm and the resulting pain or discomfort. It can also be administered for acute pain in general and for tension headache (muscle contraction headache). It acts on the spinal cord by depressing reflexes. It is sold under the brand names Lorzone, Paraflex and Muscol and in combination form as Parafon Forte, a combination of chlorzoxazone and acetaminophen (paracetamol). Possible side effects include dizziness, lightheadedness, malaise, nausea, vomiting, and liver dysfunction. Used with acetaminophen it has added risk of hepatotoxicity,. Like metaxalone, its mechanism of action is still in question. It is believed that metaxalone works by altering serotonin levels and acting as a mild MAO inhibitor. The mechanism of action of chlorzoaxazone is thought to act on Gaba-A & B receptors and voltage-gated calcium channels to a degree. General central nervous system depression is the only currently accepted aspect to its medical benefits. Elucidation of the exact mechanism of action is ongoing but there is limited study due to the existence of more effective, safe muscle relaxants (ex. diazepam, cyclobenzaprine, tizanidine), greatly limiting the potential benefit of identifying novel compounds which share chlorzoxazones mechanism of action. See also
Zoxazolamine

References
Further reading
External links
"Chlorzoxazone". Drug Information Portal. U.S. National Library of Medicine. Chloroxazone Safety Data Sheet Archived 2019-07-12 at the Wayback Machine
D.F. Marsh, U.S. Patent 2,895,877 (1959)