ABSTRACT
Sporadic tumors of the pituitary, parathyroids and adrenal cortex are unique, as their benign forms are very common, but malignant forms are exceptionally rare. Hereditary forms of these tumors occur in multiple endocrine neoplasia syndrome type 1 (MEN1). We hypothesize that the pathogenic link among the sporadic tumors of these organs of different germ layers might be represented by common molecular pathways involving the MEN1 gene and microRNAs (miR). miR-24 might be a microRNA linking the three tumor entities, but other candidates such as miR-142-3p and microRNAs forming the DLK1-MEG3 miRNA cluster might also be of importance.
Subject(s)
Adrenal Cortex Neoplasms/genetics , MicroRNAs/genetics , Multiple Endocrine Neoplasia Type 1/genetics , Parathyroid Neoplasms/genetics , Pituitary Neoplasms/genetics , Proto-Oncogene Proteins/genetics , Calcium-Binding Proteins , Cell Transformation, Neoplastic , Computational Biology/methods , Gene Expression Profiling , Humans , Intercellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Models, Theoretical , Multigene Family , Mutation , Pituitary Gland/metabolism , RNA, Long Noncoding/genetics , Smad3 Protein/metabolism , Transforming Growth Factor beta/metabolismABSTRACT
The effect of metformin on methylglyoxal (MG) metabolism was studied in a prospective non-randomized 24 weeks trial in patients with type 2 diabetes.Metformin treatment, in addition to life style intervention, significantly reduced morning glucose and HbA1c whilst body weight and BMI were only marginally reduced during the 24 week trial. Treatment significantly reduced both plasma MG and carboxymethyl-lysine (CML), a marker of oxidative stress. The reduction in MG was paralleled by a significant increase in the activity of Glyoxalase 1 (Glo1), the major route of MG detoxification, in peripheral blood mononuclear cells and red blood cells. Multivariate analysis showed that the changes in MG were dependent upon the metformin treatment.This study supports previous findings that metformin can reduce plasma MG in type 2 diabetic patients. However, given the observed increase in Glo1 activity, this reduction is due not only to the scavenging properties of metformin, but the restoration of Glo1 activity.
Subject(s)
Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Metformin/analogs & derivatives , Pyruvaldehyde/blood , Adult , Female , Humans , Lactoylglutathione Lyase/metabolism , Male , Middle Aged , Prospective StudiesABSTRACT
The endocannabinoid system contributes to the regulation of appetite, food intake and energy balance. Fatty acid amide hydrolase is responsible for degradating anandamide, a key messenger of the endocannabinoid system. C385A is a common, functionally active genetic polymorphism of the gene encoding fatty acid amide hydrolase and has been associated with overweight and obesity. Our aim was to establish whether single nucleotide polymorphism C385A has an association with polycystic ovary syndrome or its clinical features.A monocentric pilot study was performed on 63 patients with polycystic ovary syndrome and 67 healthy control subjects. Anthropometric parameters and laboratory data were acquired from subjects. The alleles of the polymorphism were detected using polymerase chain reaction and subsequent cleavage by Eco130I (StyI) restriction endonuclease verified by direct DNA sequencing.No difference was found in minor allele frequency between patient and control groups. Those patients, carrying the C385A polymorphism were associated with higher free thyroxine hormone levels. In the control group, carriers of the polymorphism had significantly lower insulin levels.Our data indicate that the C385A polymorphism of the fatty acid amide hydrolase gene is not a genetic susceptibility factor for the development of polycystic ovary syndrome. However, the polymorphism might have a role in influencing the synthesis or metabolism of different hormones including thyroxin and insulin.
