Monthly Archives: August 2014

One Single Enzyme May be the Key to the Development of Diabetes

One Single Enzyme May be the Key to the Development of Diabetes

Reference: August 14th issue of Molecular and Cellular Biology

There may just one enzyme the gets us in trouble when we get overweight.  About 40% of Americans are currently in that state of diabetes or prediabetes, and that’s if you count a blood sugar over 100.  I believe the Whitehall Study shows us that a blood glucose over 86, two hours after a meal is what really matters, as every point over 86 means your risk of developing diabetes increases by 5%.   So, 100 and 126 are just arbitrary numbers that we have picked for levels of increasing risk.  If we take the Whitehall study, my experience (there is no data) is that closer to 90% of us are “not perfect”.

Developing Type II diabetes means you have insulin around, but you are insulin resistant and your fat cells just can’t respond to insulin.  If you measure insulin levels routinely, you see folks who have normal blood sugars, but very high insulin levels – and they are universally overweight.   Obesity makes for larger fat cells that aren’t able to respond to the insulin signal to take up glucose or fat, so your glucose and your fat levels in your blood increase.

What’s the critical enzyme from this study?  One called 12-Lipooxygenase, or 12-LO.  It is present ONLY when people become overweight.   12-LO manufactures small molecules called  HETEs (hydroxyeicosatetraenoic acid) which damage the mitochondria in the pancreas cell.  The mitochondria are the power plants that produce energy for the cell.  With damaged mitochondria, the cells can’t produce enough insulin to keep up with the demand caused by insulin resistance promoted by obesity.

The researchers genetically engineered the mice to have no 12-LO enzyme at all in their pancreas glands, then fed them high fat diets versus low fat diets.  The researchers fed both control and knockout mice the Western Diet – high in saturated fat – and both sets got obese. And insulin resistant.   Then, they looked at their pancreas glands.  The Knockout mice with no 12-LO still had intact and undamaged pancreas glands whereas the control mice had damaged pancreas glands. This implicates 12-LO as the missing ingredient of causing damage that then leads to pancreas failure and overt diabetes.    12-LO may be the cause of pancreatic failure that ensues when we become obese and our blood sugar starts climbing and we become insulin resistant.

What the authors don’t address or explain is that a high fat diet causes obesity mostly when it’s combined with refined sugars and carbohydrates.  That’s the real problem with the “Western Diet”.  Fat does not cause the release of insulin, whereas carbohydrates do.  To remain trim and fit, and not develop diabetes one needs to eat fat.   (Please read the book The Big Fat Surprise by Nina Teicholz).

WWW. What Will Work for Me.  I’m not sure I completely agree with the explanations this author provides about diabetes, but I love the discovery of a single specific enzyme that causes damage to the pancreas gland and causes it to finally poop out.  We can’t let low grade sugar persist without eventually running the gauntlet of overt diabetes.


Pop Quiz

  1. 12-LO in present in pancreas cells only when we become obese.  T or F


  1. 12-LO makes damaging molecules that injure our pancreas glands by damaging their mitochondria, which leads to “power failure” and the inability to make sufficient insulin to meet demand.  T  or  F


  1. About 40% of American’s have prediabetes or diabetes.  T or F

True if you use the measurement of 100 for glucose, but many more if you use the Whitehall data to support 86 as the normal level

  1. I can lower my risk for diabetes by losing weight.  T or F


  1. So, I can get rid of 12-LO by losing weight

Yup, yup.

Marijuana and Multiple Sclerosis

Marijuana and Multiple Sclerosis

Reference:   American Academy of Neurology Guidelines 2014

Time to get serious about this strange plant, cannabis.  In this review, Dr. Koppel reviews 33 studies of  cannabis, THC or oral cannabis extract in the treatment of MS, seizures, Parkinson’s and other disorders.  It included multicenter trials that also had placebo controlled studies.

Conclusion of the report: there is clearly a place for cannabis in the treatment of spasticity, non-neuropathic pain, urinary dysfunction and patient-perceived quality of life in people with multiple sclerosis.   So far there hasn’t been enough evidence to support its use in Huntington’s disease or Tourette’s syndrome, and suggests that it may not be useful in epilepsy (flying in the face of strong evidence for children with some specific forms of intractable epilepsy.)

This column wrote a series of articles about the endocannabinoid system in our brains several years ago (search in  We have found CB-1 receptors in the hippocampus, basal ganglia, cerebellum, spinal cord and peripheral nerves, but not in the brainstem.  The lack of receptors in the brain stem may be why there have been virtually no reported fatalities from “overdosing” with marijuana, as your brainstem is the source of consciousness and breathing.  You may be mellow, but now out.  CB-2 receptors are found mostly outside the brain.  Cannabis has about 60 active compounds of which THC or tetra-hydrocannabinol is the most famous.   Each of them appears to have variable activity in the various receptors.   Considering the neuroactivity that has been discovered, it’s likely going to be a while figuring out just what compound does what.    Studying one at a time is probably going to be the final determinant of what does what.  However, the mix of all of them is what the plant offers and that’s what we know for now.

With MS, oral cannabis extract was found to clearly help central pain or painful spasms.  It also was found to be helpful at reducing bladder voids per day, something that is the bane of bedbound patients.  And finally, some MS patients appeared to have an improved sense of well being when taking cannabis, though not all.   And that may be the most valuable of all.

Is the use of MS without risk?   If there are no receptors in the brainstem, and you can hardly overdose, is it dangerous?  Very high doses of THC have been known to induce psychosis, dysphoria and extreme anxiety.  Dr Koppel quotes a risk of about 1% for serious neurological or psychiatric side effects.   The cannabinoids do inhibit the P-450 enzyme system of the liver, which may radically alter pain medication effectiveness.   Because so many drugs are processed through the P-450 system, we may not know all the side effects yet.  Once legalized, this is a topic that can be further studied.

WWW.  What will work for me.  Marijuana is now bursting on the scene with the legal changes happening in America.  I personally know several folks who have travelled to Colorado to get relief from all their systems of various illnesses.  To some beneficial effect.   There seems to be a whole new chapter of opportunity opening up as we discover the “endocannabinoid” system in our brains, and how we can manipulate it to our benefit.  Interesting the source!  Time for more research.  I’m intensely interested, and hopeful.  I want to be helpful, when it makes clinical, legal sense.

Pop Quiz

  1. Marijuana is an illegal drug and should remain that way.  T or F

Whoa Nellie, it’s becoming legal in multiple venues.  Times are changing and there is evidence it may be a useful drug for much more than Saturday night parties

  1. Marijuana has some serious side effects.  T or F

True. This review article estimates that about 1% of folks have serious psychiatric symptoms, up to and including pyschosis.

  1. With Multiple Sclerosis, marijuana helps reduce painful spasms.  T or F


  1. In MS, marijuana helps increase an overall sense of well being.  T or F


  1. Marijuana has at least 60 known neuro-active compounds.  T or F


  1. Marijuana may block the effectiveness of some pain killers. T or F

True – and many other drugs – not known yet until it is legal.

  1. My opinion, for what it’s worth – it’s better to legalize it and stop pumping money into the drug gangs, and educate our kids to its dangers.  But make it regulated, legal, medically available and taxed – not illegal and unavailable.