ABSTRACT
6-((2-Fluoro-3-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)propyl)amino)-2,3-dihydro-1H-inden-1-one is a potent drug-like G protein-coupled receptor 119 (GPR119) agonist. It is hoped that this compound would be instrumental in probing the pharmacological potential of GPR119 agonists.
Subject(s)
Indenes/chemistry , Indenes/pharmacology , Piperidines/chemistry , Piperidines/pharmacology , Receptors, G-Protein-Coupled/agonists , Animals , Cell Line , Glucose Tolerance Test , Humans , Indenes/chemical synthesis , Indenes/pharmacokinetics , Male , Mice , Mice, Inbred C57BL , Piperidines/chemical synthesis , Piperidines/pharmacokinetics , Rats , Rats, Wistar , Receptors, G-Protein-Coupled/metabolismABSTRACT
We disclosed a novel series of G-protein coupled receptor 119 (GPR119) agonists based on a bicyclic amine scaffold. Through the optimization of hit compound 1, we discovered that the basic nitrogen atom of bicyclic amine played an important role in GPR119 agonist activity expression and that an indanone in various bicyclic rings was suitable in this series of compounds. The indanone derivative 2 showed the effect of plasma glucose control in oGTT and scGTT in the rodent model.
Subject(s)
Amines/chemistry , Bridged Bicyclo Compounds/chemistry , Hypoglycemic Agents/chemical synthesis , Indans/chemical synthesis , Pyrimidines/chemical synthesis , Receptors, G-Protein-Coupled/agonists , Amines/chemical synthesis , Amines/pharmacology , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , Glucose Tolerance Test , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Indans/chemistry , Indans/pharmacology , Mice , Mice, Inbred C57BL , Protein Binding , Pyrimidines/chemistry , Pyrimidines/pharmacology , Receptors, G-Protein-Coupled/metabolism , Structure-Activity RelationshipABSTRACT
OBJECTIVES: There is little information on lipid metabolism after sauna treatment in the literature. The present research is aimed to determine the influence of sauna baths on fat metabolism in young women. MATERIALS AND METHODS: Twenty healthy, eumenhorreic, female volunteers (19-21 yr old) were exposed to Finnish sauna bath seven times every second day. In group I (n = 10) each time the sauna treatment lasted 30 min, whereas in group II (n = 10) 40 min with 5-minute break to cool down. Body mass, heart rate and blood pressure were measured before and after sauna bath. Rectal temperature was monitored during stay in sauna room. Prior to the sauna bath and during its last two minutes the minute oxygen uptake and the level of CO2 exhalation were analyzed in the exhaled air, and the respiratory quotient RQ was calculated. In the blood samples collected before the sauna bath and immediately afterwards hematocrit, hemoglobin, and lipid profile--total lipids, free fatty acids, total free fatty acids, triacylglycerols, total cholesterol (TC), high density lipids (HDL), low density lipids (LDL) were analyzed. RESULTS: Rectal temperature was lower in the last sauna bath than in the first one. Losses of plasma were greater during the seventh bath than during the first one. Acceleration of the metabolism of lipids occurs after every sauna bath. A reduced level of TC and LDLC and a raised level of HDL was observed after repeated sauna baths. CONCLUSION: After 2 weeks of repeated sauna session some changes in total cholesterol and concentration of LDLC were observed, while concentration of HDLC increased after 7th sauna bath in group I. Those kinds of changes may be good prognoses of ischemic heart disease prevention, but further research on the influence of sauna on fat metabolism is needed.
Subject(s)
Cholesterol, HDL/blood , Cholesterol, LDL/blood , Fatty Acids, Nonesterified/blood , Steam Bath , Triglycerides/blood , Body Temperature , Calorimetry, Indirect , Female , Humans , Young AdultABSTRACT
The influence of extremely low temperatures on the human body and physiological reactions are not fully recognized. It has been postulated that cryostimulation could modify immunological reactions, leukocytes mobilization and levels of cytokines. The aim of this research was to estimate the influence of a ten sessions 3-min-long exposures to cryogenic temperature (-130 degrees C) on the white blood cell (WBC) count, level of IL6 and the total oxidative and antioxidative status in 15 young, clinically healthy men. Blood samples were obtained in the morning before cryostimulation, again 30 min after treatment and the next day in the morning, both during the first and tenth session. The WBC count, level of IL6 and total lipid peroxides as the total oxidative status and the total antioxidative status (TAS), were measured. After completing a total of ten whole-body therapy sessions a significant increase in WBC count, especially lymphocytes and monocytes was noted. There was an increase in level of IL6 after first and the last cryostimulation the most pronounced after tenth session. On the contrary the TAS level decreased significant after the treatment. It was concluded that repeated expositions to extremely low temperatures use in cryostimulation have mobilization effect on immunological system.
