When blood sugar is falling, the stopper built into the body is the release of glucagon from the alpha cells of the pancreas which stimulates the release of glucose from the liver (but only if your adrenaline is flowing). However, when hypoglycemia is due to injected insulin - the stopper isn't entirely in place. Scientists explain how epinephrine (adrenaline) plays a major role in regulating glucose in times of low blood sugar and how this response could be adversely affected by the use of beta-blockers.

During insulin-induced hypoglycemia in dogs, the roles of adrenaline and glucagon were evaluated. The dogs fasted overnight to remove excess glucose from the blood. The dogs also had their adrenal glands removed. The adrenal glands are the source of adrenaline. Adrenaline is released into the bloodstream in response to physical or mental stress,to initiate the stimulation of glucose, among many other functions. Adrenaline and insulin were released at two different rates: a basal rate or a variable rate to simulate an adrenaline response. When the blood sugar fell to 42 mg/dL, the dogs in the basal rate group failed to release glucagon, but the simulated adrenaline response group increased normally. The liver response to releasing glucose fell in the basal group but increased in the simulated adrenaline response group. The researchers conclude that adrenaline must be responsible for this critical response to insulin-induced hypoglycemia.

Beta blockers are a common class of prescription drugs that counteract the stimulatory effects of adrenaline. Diabetics who inject insulin and take beta-blockers should be extra cautious of hypoglycemia. Hypoglycemic unawareness is already established for diabetics injecting GM insulin (genetically modified human insulin). Given the side effects of beta blockers, there is greater reason to be more aware of hypoglycemis unawareness -- yes, oxymoron. Those individuals who are on the brink of diabetes should avoid beta-blockers at all costs, according to a study in The Lancet (January 2007) beta-blockers used for hypertension increase a patient's risk of developing diabetes.

Knocking out the gene for a peptide associated with insulin was shown to protect mice against the harmful effects of a high-fat diet. Urocortin 3 plays a role in the increased production of insulin in response to high caloric intake in animals.

Scientists found that by removing the urocortin 3 gene from mice, they did not develop the age-related insulin resistance and high blood sugar observed in the normal control mice. The metabolisms of normal mice were compared to the metabolisms of those without the urocortin 3 gene. When placed on a high caloric diet for three months, the mice without the urocortin 3 gene packed on the same amount of weight but had lower insulin levels. But these mice also had lower blood sugar, improved glucose tolerance curves and they did not develop the fatty livers the control mice experienced.

Scientists hypothesize that by curtailing the abnormally high insulin levels, they were able to manipulate insulin sensitivity and avoid some of the untoward consequences of the high food intake and weight gain. Like many of us diabetics already know too well - while insulin is effective at lowering blood sugar it also promotes fat storage. This is a natural protective response to prepare for times when food may not be available. When insulin is produced at too high a level for too long, the body becomes insulin resistant and blood sugar and certain blood lipids gradually creep up, which can cause progressive damage to multiple organs.

Urocortin 2 and urocortin 3 are part of the system that governs the body's response to insulin. Scientists already know that mice on a high-fat diet do better if either urocortin 2 or urocortin 3 is removed. Now they want to know if the mice will respond even better if both are missing. Such results may instruct us how best to develop therapeutic means to exploit these powerful effects.