Glucose-induced Effects and Joker Function of Glucose: Endocrine or Genotoxic Prevalence?

Abstract The steady increase in chronic “glycemic load” is characteristic for modern times. Among myriad of glucose functions, two principals can be emphasized: first, ENDOCRINE (in particular, ability to induce insulin secretion) and second, DNA-DAMAGING related to formation of reactive oxygen species (ROS). It was suggested by us earlier that a shift in the ratio of mentioned functions reflects a possible “joker” role of glucose as an important modifier of human pathology. Therefore, we embarked on a study to investigate AN INDIVIDUAL effect of peroral glucose challenge on serum insulin level and ROS generation by mononuclears (luminol-dependent/latex-induced chemiluminescence) in 20 healthy people aged between 28-75. Concentrations of glucose, blood lipids, carbonylated proteins, malondialdehyde, leptin and TNF-α were determined as well. On the basis of received data two separate groups could be distinguished: one (n=8), in which glucose stimulation of ROS generation by mononuclears was increased and relatively prevailed over induction of insulin secretion (state of the so called glucose-induced genotoxicity, GIGT), and another (n=12), in which signs of GIGT were not revealed. People who belonged to the first group were characterized with a tendency to lower body mass index, blood leptin and cholesterol and to higher TNF-α concentration. Thus, if joker function of glucose is realized in “genotoxic mode”, the phenotype (and probably genotype) of subjects may be rather distinctive to the one discovered in glucose-induced “endocrine prevalence”. Whether such changes may serve as a pro-mutagenic or pro-endocrine basis for the rise of different chronic diseases or, rather, different features/aggressiveness of the same disease warrants further study.