Insulin Therapy and Alzheimer’s – Could Cyclodextrin Sugar Act on Insulin and Glucose Metabolism?
Recently reports in the news shows how insulin therapy may be a treatment for Alzheimer’s. Basically, a low dose of insulin has been found to suppress the expression in the blood of four precursor proteins involved in the pathogenesis of Alzheimer’s disease, according to research by University at Buffalo endocrinologists. Paresh Dandona, MD, PhD, University at Buffalo is a senior author on the study.
I am very interested in insulin therapy for Addi and Cassi and I have been looking into this along with a drug called Rosiglitazone. I wonder if I am already doing insulin therapy by giving the twins the sugar compound cyclodextrin into their bodies and brains? I think I’ll email Paresh Dandona about it.
Addi and Cassi have major disruption in glucose metabolism in their brains. Dr. Harry Chugani and his team at Children’s Hospital of Michigan discovered this a few years ago in the twins and it is spreading out of control based on our last PET scan. Dr. Chugani and team are publishing a paper about the glucose metabolism PET based brain biomarker in Niemann Pick Type C disease.
For over a year, I have been looking into whether or not hydroxy-propyl-beta-cyclodextrin (HPBCD) might have some sort of effect on insulin and glucose metabolism in the body and brain.
I found these very interesting references:
- International Journal of Molecular Sciences (2009): The objective of this study was to elucidate the effects of hydroxylpropyl- B-cyclodextrin (HPBCD) on the in vitro stability of insulin. It was found that HPBCD had positive effects on the stability of insulin in acid and base and under high temperature conditions. Furthermore, use of HPBCD could also increase the stability of disulfide bonds which are important to the conformation of insulin. Through 1H-NMR experiments it was found that the protective effect of HBPCD was due to complexation with insulin. The results suggest that the presence of HPBCD could improve the stability of insulin in different environments.
- Abulrob et.al. (J Neurochem. 2005 Mar;92(6):1477-86) demonstrated the neuroprotective activity of some cyclodextrin derivatives against oxygen-glucose deprivation (OGD), N-methyl-D-aspartic acid (NMDA) and glutamate in cortical neuronal cultures. Although all Cyclodextrin complexed with NMDA or glutamate, only beta-, methylated beta-and sulfated beta-CDs displayed neuroprotective activity and lowered cellular cholesterol.
I have been asking our researchers to see if they can conduct microPET on the Niemann Pick Type C mice to see if they can find a hypometabolism issue in the brains of the mice like they find in my identical twins. If found, researchers could give the NPC mice the cyclodextrin and test as to whether or not it has an effect on insulin and glucose metabolism in the brain. If so, this could be a very important finding that could bolster the University at Buffalo’s work.
Also, one of the things I find really interesting is there is a rare disease called Ataxia – telangiectasia that I think provides further clues to neurodegeneration. In Ataxia – telangiectasia, there are issues with glucose and insulin receptors: http://www.ncbi.nlm.nih.gov/pubmed/651946
Both Niemann Pick Type C and Ataxia – telangiectasia there is massive loss of Purkinje cells in the brain — loss of Purkinje cells in one of the first signs in NPC disease. Why the massive loss of Purkinje neurons in Niemann Pick Type C and Ataxia – telangiectasia? What is the connection point causing loss of Purkinje neurons? I think it might be glucose metabolism or insulin utilization.
Given the glucose metabolism issue we have found in Addi and Cassi’s brains and the ataxia which is one of the first symptoms of the disease, maybe glucose metabolism and insulin issues are a core issue in NPC? I read that the cerebellum is largely fueled by glucose and the cerebellum is where Purkinje neurons are located!
Steve Walkley’s work shows that cyclodextrin rescues Purkinje neurons in the NPC mouse model – could it be acting on glucose metabolism or insulin? Could cyclodextrin rescue Purkinje cells in Ataxia – telangiectasia?