Diabetes is a stressful disease, but some diabetics are uniquely sensitive to stress. Anything that stirs up emotion, or aggravation, or worry, also raises their blood sugar levels. Even when these diabetics are extremely careful about diet, insulin, medication, and exercise, their blood glucose levels are hard to control, and in times of extreme stress, medication and even insulin hardly work at all.
These unfortunate men and women suffer a form of type 2 diabetes partially caused by a mutation in a gene called alpha(2A)-AR. This gene causes insulin-producing beta cells in the pancreas to be covered with an unusually large number of receptor sites for the stress hormone adrenalin (epinephrine). When adrenalin binds to pancreatic receptor sites, beta cells release less insulin. Swedish diabetes researcher Dr. Anders Rosengren, head of the translational diabetes research group at Lund University Diabetes Center in Malmo, compares the phenomenon to driving a car with the parking brake on. No matter how hard you press on the gas pedal, the brakes keep you from going forward. Surprisingly, Rosengren and his colleagues have found a remedy for this condition in the herb-derived erectile dysfunction helper yohimbine.
Yohimbine, an Almost-Forgotten Treatment for ED
Before there were Cialis, Levitra, and Viagra, yohimbine was a preferred natural treatment for erectile dysfunction. Derived from the bark of the African yohimbe vine, yohimbine hydrochloride is a standardized, reliably dosed form of the active chemical of the herb that works by binding to receptors in the blood vessels supplying the penis, causing a localized increase in blood pressure that powers an erection and a generalized sensation of excitement that piques interest in sex. (In overdoses, however, the drug can bind to different receptors causing a generally lower blood pressure affecting the entire body.)
Yohimbine in the Pancreas
Yohimbine can also bind to the adrenalin receptors on the insulin-producing beta cells of the pancreas. This blocks the effects of adrenalin itself, so the pancreas is free to release insulin more normally. Most diabetics who have mutations of the alpha(2A)-AR gene also have other genetic mutations that contribute to diabetes, so yohimibine is not a complete cure for diabetes, but the effect is large enough that blood sugars become easier to manage with small doses of other medications.
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A Downside to Yohimbine Treatment
The problem with using yohimbine to treat diabetes is that can lower systemic blood pressure. In the same way that too much Viagra can cause a man to pass out (or, in combination with blood pressure lowering drugs called nitrates, even enter a fatal cardiac arrest), too much yohimbine can cause both male and female users to have unacceptably low blood pressure. There can be orthostatic hypotension, a sudden lowering of blood pressure when moving from a seated position to a standing position that can cause loss of consciousness. There can be extreme fatigue, or just a general loss of energy that makes getting about one's daily routine very difficult. Also, men who take yohimbine are subject to having erections at inappropriate times and in inappropriate places.
Gene-Based Diabetes Treatments, A New Frontier in Diabetic Control
Moreover, the amount of yohimbine used in the study was four times as much as is generally needed to induce an erection in men or a sexually receptive state in women. However, the results of administering the herb chemical were clearly beneficial for diabetes control. In type 2 diabetics who had two copies of the relevant gene, treatment with yohimbine increased insulin production as much as 79 percent. In people who do not have two copies of the relevant gene, however, the treatment would have no effect, at least not blood sugar levels. It could still cause unwanted erections in male users.
New diabetes treatments, however, are likely not be based on the principle that "the same treatment (other than insulin) works for every diabetic." New diabetes treatments are likely to be tailored to genetic differences in the diabetics who take them. Here are two examples of how this principle is already being used in treating diabetes:
- In the late 1990's, a class of drugs called the thiazolidinediones, or TZD's (Actos and Avandia) seemed to be a wonder drug for type 2 diabetes. They lowered blood sugar levels by activating PPAR-gamma receptors on the surfaces of fat cells. Even diabetics who had horrible diets could get good results by taking these drugs. However, in a few years, diabetics and doctors learned that easy blood sugar control with TZD's came at a price. Actos and Avandia stimulated the development of stem cells intended to become bone cells or red blood cells into fat cells. Enormous weight gain became all too common among users of these drugs. Because this weight gain involved the creation of new fat cells, returning to normal weight was not a simple matter of diet and exercise. Several TZD's were banned entirely, and Actos and Avandia now come with stern warnings. However, it is now possible to do genetic testing for the number of PPAR-gamma binding sites on fat cells. Some diabetics have too many binding sites and will suffer side effects form the drugs. Some diabetics will have too few binding sites and not respond to the drugs. Some diabetics will have just the right number of binding sites and respond well to Actos and Avandia. For these diabetics, TZD's may truly be wonder drugs.
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- In some parts of the world, up to one fifth of the population has a mutation in the genetic code from the production of an enzyme called methylene tetrahydrofolate reductase, or MTHFR. In these people, the body lacks an enzyme for the efficient conversion of folic acid to methylfolate, its active form. People who have the MTHFR mutation suffer especially severe MTHFR symptoms as complications of diabetes that can be prevented simply by taking a safe, inexpensive, and widely available B vitamin supplement, methylfolate, costing just $5 to $10 a month, and avoiding folic acid supplements. Testing for this mutation is so common that it is now covered by health insurance in the United States and most other countries, but only a small percentage of diabetics who would benefit from MTHFR testing know about the benefits of the supplement.
Gene-based therapies for diabetes can be tremendously successful for the diabetics who need them. Ask you endocrinologist about appropriate testing that lead to a much easier experience of managing your condition.
Sources & Links
- Tang Y, Axelsson AS, Spégel P, Andersson LE, Mulder H, Groop LC, Renström E, Rosengren AH. Genotype-based treatment of type 2 diabetes with an α2A-adrenergic receptor antagonist. Sci Transl Med. 2014 Oct 8. 6(257):257ra139. doi: 10.1126/scitranslmed.3009934.PMID: 25298321.
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- Photo courtesy of thedailyenglishshow: www.flickr.com/photos/thedailyenglishshow/18952373061/
- Photo courtesy of thedailyenglishshow: www.flickr.com/photos/thedailyenglishshow/18923209956/