Posted on 09/26/2007 10:02:14 AM PDT by Red Badger
Insulin, it turns out, may be as important for the mind as it is for the body. Research in the last few years has raised the possibility that Alzheimer’s memory loss could be due to a novel third form of diabetes.
Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer’s disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer’s removes insulin receptors from nerve cells, rendering those neurons insulin resistant. (The protein, known to attack memory-forming synapses, is called an ADDL for “amyloid ß-derived diffusible ligand.”)
With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer’s disease, the Northwestern study sheds light on the emerging idea of Alzheimer’s being a “type 3” diabetes.
The new findings, published online by the FASEB Journal, could help researchers determine which aspects of existing drugs now used to treat diabetic patients may protect neurons from ADDLs and improve insulin signaling in individuals with Alzheimer’s. (The FASEB Journal is a publication of the Federation of American Societies for Experimental Biology.)
In the brain, insulin and insulin receptors are vital to learning and memory. When insulin binds to a receptor at a synapse, it turns on a mechanism necessary for nerve cells to survive and memories to form. That Alzheimer’s disease may in part be caused by insulin resistance in the brain has scientists asking how that process gets initiated.
“We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed,” said William L. Klein, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, who led the research team. “Instead, they are piling up where they are made, in the cell body, near the nucleus. Insulin cannot reach receptors there. This finding is the first molecular evidence as to why nerve cells should become insulin resistant in Alzheimer’s disease.”
ADDLS are small, soluble aggregated proteins. The clinical data strongly support a theory in which ADDLs accumulate at the beginning of Alzheimer’s disease and block memory function by a process predicted to be reversible.
In earlier research, Klein and colleagues found that ADDLs bind very specifically at synapses, initiating deterioration of synapse function and causing changes in synapse composition and shape. Now Klein and his team have shown that the molecules that make memories at synapses -- insulin receptors -- are being removed by ADDLs from the surface membrane of nerve cells.
“We think this is a major factor in the memory deficiencies caused by ADDLs in Alzheimer’s brains,” said Klein, a member of Northwestern’s Cognitive Neurology and Alzheimer's Disease Center. “We’re dealing with a fundamental new connection between two fields, diabetes and Alzheimer’s disease, and the implication is for therapeutics. We want to find ways to make those insulin receptors themselves resistant to the impact of ADDLs. And that might not be so difficult.”
Using mature cultures of hippocampal neurons, Klein and his team studied synapses that have been implicated in learning and memory mechanisms. The extremely differentiated neurons can be investigated at the molecular level. The researchers studied the synapses and their insulin receptors before and after ADDLs were introduced.
They discovered the toxic protein causes a rapid and significant loss of insulin receptors from the surface of neurons specifically on dendrites to which ADDLs are bound. ADDL binding clearly damages the trafficking of the insulin receptors, preventing them from getting to the synapses. The researchers measured the neuronal response to insulin and found that it was greatly inhibited by ADDLs.
“In addition to finding that neurons with ADDL binding showed a virtual absence of insulin receptors on their dendrites, we also found that dendrites with an abundance of insulin receptors showed no ADDL binding,” said co-author Fernanda G. De Felice, a visiting scientist from Federal University of Rio de Janeiro who is working in Klein’s lab. “These factors suggest that insulin resistance in the brains of those with Alzheimer’s is a response to ADDLs.”
“With proper research and development the drug arsenal for type 2 diabetes, in which individuals become insulin resistant, may be translated to Alzheimer’s treatment,” said Klein. “I think such drugs could supercede currently available Alzheimer’s drugs.”
Source: Northwestern University
Thank you for responding back to me. My husband takes Metformin and Actos (since he was diagnosed a year and a half ago). He was having trouble with his feet, lower legs. Bee sting feeling; heaviness; clumsiness. Awkard unsteady gait. With all of the other really bad diagnonsis he could have had, we were relieved to hear it was from diabetes (they were originally thinking neurological). The neuropathy is his main concern right now. His numbers are fairly stable (he was spiking in early months of treatment). He is in the low 100s and never usually over 130. He was over 400 when first diagnosed. He walks; but can’t run with the kids or our dog like he used too...he used to coach soccer and baseball and now just helps out when he can (having a good day). The med you are referring to is advertised for ‘bee sting’ sensation...I remember seeing that once or twice (and then it went away).
Alzheimers doesn't happen to old folks, that's "senile dementia." Alzheimers happens to people in their forties and fifties.
PaMom
There is a healthy sweetner that is not a carb; it's called Stevia. Used correctly, it tells your tongue 'sweet,' but has no effect on anything else, unlike aspertame which has caused some to go blind due to the conversion to methanol that occurs when it is metabolized.
over here ...
Yes it is. It's carbon, hydrogen, and oxygen, (C2H5OH) just like all the other carbs, and it is far more harmful to a diabetic than sucrose.
Bump to #66. Pingees, please give F@H a look. It’s literally painless (much like DM itself).
Thanks, TxB.
Because, based on the latest information about Avandia, it is acurate.
The literature is available from Glaxo for Avandia and Takeda Pharmaceuticals for Actos. As well as recently published stories about Avandia.
They are both drugs of the class thiazolidinedione but they are slightly different chemically. Literature from Takeda states that its product, Actos does not pose the cardio-vascular risk that Avandia does. So far, the FDA has agreed.
That's why I wrote what I did. Reporting published facts.
While alcohols are "OH group attached to a saturated carbon". As your example shows, alcohols can have a very different hydrogen to oxygen ratio.
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