Day 1 :
Colorado State University, USA
Keynote: Why clinical trials that reduce glucose levels fail to prevent complications in diabetic patients: Tests support an alternative hypothesis for pathogenesis
Time : 09:-10:00
Douglas N Ishii received his BA in Biochemistry from University of California, Berkeley and PhD in Pharmacology from Stanford University Medical School and conducted Postdoctoral work in Neurobiology at Stanford. He became Assistant then Associate Professor of Pharmacology at Columbia University, New York City. He is a Professor of Biomedical Sciences at Colorado State University. He served on various scientific study sections for National Science Foundation, National Institutes of Health and The Juvenile Diabetes International Foundation. Press coverage on his laboratory’s research on pathogenesis of diabetic neurological complications, and cause of brain atrophy in Alzheimer’s disease, includes articles in Der Spiegel, Hong Kong Standard, NY Times, LA Times, Denver Post, Chicago Tribune, ABC News, Forbes News, USA Today, National Public Radio, and elsewhere. Nineteen patents were awarded based on this research.
Statement of Problem: Meta-analysis of outcomes on 34,533 Type 2 diabetic patients shows that intensive lowering of glucose levels
does not prevent neuropathy, retinopathy, nephropathy, cardiovascular death, nor excess mortality. Nor does lowering of glucose levels prevent complications in approximately 40% of type 1 patients. Exposing patients to adverse effects from unbeneficial drugs is unjustified, yet remains standard therapy. The development of meaningful novel treatments awaits an alternative hypothesis for
pathogenesis of diabetic complications.
Methodology & Theoretical Orientation: Insulin and insulin-like growth factors (IGFs) are neurotrophic factors. The inter-related
hypotheses were developed that diminished insulin and IGF activities is the dominant cause of neurological complications, and that replacement of such activities should ameliorate diabetic complications irrespective of unabated hyperglycemia. These hypotheses were tested by infusing IGFs, insulin, or their combination into diabetic rats to determine whether neuropathy is alleviated under conditions in which hyperglycemia remains unabated.
Conclusion & Significance: IGF mRNA levels are reduced in peripheral nerves, brain and spinal cord in diabetes. Replacement IGF infusion prevented impaired sensory and motor nerve regeneration, hyperalgesia, abnormal ultrastructure in autonomic axons, loss of epidermal nerve fiber density, and poor gastric wound healing despite undiminished hyperglycemia. Tiny doses of insulin
and/or IGF were infused into diabetic rat brains under conditions that did not reduce hyperglycemia. A decrease in total mRNA, protein, and DNA levels was associated with brain atrophy and impaired learning/memory in diabetic rats. Insulin and IGF i.c.v. infusion prevented all such disturbances despite unabated hyperglycemia. Insulin and IGFs are master switches controlling the levels of hundreds of proteins in brain; loss of protein regulation, not hyperglycemia, is proposed as the most likely pathogenic cause for diabetic complications. Governments should manufacture clinical grade IGF (off- patent). Clinical trials are urgently needed to test insulin/IGF therapy.
University Grenoble Alpes, France
Time : 10:00-10:45
Serge P. Bottari obtained his MD and his PhD degrees at the Free University Brussels, Belgium. He is specialized in OB/GYN and also obtained a PhD in Biochemistry. He was a Post-Doctoral Fellow and Research Associate at UC San Francisco. After having been a Project Leader at Sandoz and Ciba-Geigy in Basel, Switzerland, he became Professor of Cell Biology at the Medical School and Head of Endocrine Biology at the University Hospital in Grenoble, France, in 1993. He published over 65 articles in premium journals and is a member of several editorial boards. His current work focuses among others on the molecular mechanisms involved in insulin resistance and on the development of novel diagnostic tools.
Insulin resistance (IR) affects more than half of the adult population worldwide. Type 2 diabetes (T2D), which often follows in the absence of treatment, affects more than 400 million people and represents more than 10% of the health budget in industrialized countries. A preventive public health policy is urgently needed in order to stop this constantly progressing epidemic. Indeed, early management of IR does not only strongly reduce its evolution towards T2D but also strongly reduces the appearance of cardiovascular comorbidity as well as that of associated cancers. There is however currently no simple and reliable test available for the diagnosis or screening of IR and it is generally estimated that 20% of diabetics are not diagnosed. We therefore developed an ELISA for the quantitative determination of a novel circulating biomarker of IR, IRAP (Insulin-Regulated Amino Peptidase, EC 22.214.171.124). IRAP is associated with and translocated in a stoechiometric fashion to the plasma membrane together with GLUT4 in response to insulin in skeletal muscle and adipose tissue. Its extracellular domain (IRAPs) is subsequently cleaved and secreted in the blood stream. In T2D, IRAP translocation in response to insulin is strongly decreased. Our patented sandwich ELISA is highly sensitive (≥ 10.000- fold normal fasting concentrations) and specific, robust and very cost-effective. Dispersion of fasting plasma concentration values in a healthy population is very low (101.4±15.9 μg/ml) as compared to insulin and C-peptide. Results of pilot studies indicate an excellent correlation between IRAPs levels and insulin sensitivity. We therefore think that plasma IRAPs is a direct marker of insulin sensitivity and that the quantitative determination of its plasma levels should allow large-scale screening of populations at risk for IR and T2D; thereby allow the enforcement of a preventive health policy aiming at efficiently reducing this epidemic.
Chonbuk National University, South Korea
Yoon-Bong Hahn is a Fellow of Korea Academy of Science and Technology, Director of BK21 Center for Future Energy Materials and Devices, Director of National Leading Research Lab for Hybrid Green Energy and Head of Semiconductor and Chemical Engineering School, Chonbuk National University (CBNU). He joined CBNU in 1991 prior to which he worked for LG Metals Research Center from 1988-1991 after he received his PhD in Metallurgical Engineering from University of Utah in 1988. His main research interest is the synthesis of metal and metal oxide nano structures and their applications for optoelectronic devices and chemical and biological sensors, resulting in over 280 peer-reviewed SCI papers and 14 patents. He co-authored 6 books including “Metal Oxide Nanostructures and Their Applications” published in March 2010 by American Scientific Publishers. He received Asian Energy Technology Award 2017 by International Association of Advanced materials, Rudolf A Marcus Award for outstanding research work in the field of Chemical Science in 2016, the ACerS Global Ambassador Award 2016 conferred by the American Ceramic Society, the Scientist of the Month Award in 2011 by Korea Ministry of Education, Science and Technology, the CBNU’s Best Research Professor Award consecutively in 2008-2010, and top 100 scientists award four times in 2005, 2011, 2014 and 2015 accredited by International Biographical Center, Cambridge, UK.
Nanotechnology revolution has led to the nano fabrication of sensor devices for rapid and specific identification of chemical/ biological species. However, the development of multiplexed nanoscale biosensor for simultaneous detection of different analytes still remains a major challenge at the nanotechnology frontier. It is well recognized that diabetes mellitus is a metabolic disorder resulting in an abnormal blood glucose level and activation of several metabolic pathways related to inflammation and apoptosis events. Heart disease and stroke due to excess cholesterol in blood is the leading cause of death and disability, and kidney failure due to excess urea is caused by urea cycle disorders. We have developed metal-oxide nanostructures based, integrated field-effect transistors (FETs) array biosensor with simultaneously immobilizing GOx, ChOx and Ur enzymes on three separated FET arrays. In this lecture, we report a novel straight forward approach for simultaneous and highly selective detection of multianalytes (i.e., glucose, cholesterol and urea) with the FETs array biosensor without interference in each sensor response. Compared to analytically measured data, performance of the FETs array biosensor is found to be highly reliable for rapid detection of multianalytes in mice blood, serum and blood smaples of diabetic dogs. The development of an integrated, low-cost FETs array biosensor will produce quick detection under critical patient conditions, early identification of disease/disorder, and also have an enormous impact on the future generations.