ABSTRACT
G protein-coupled receptor 119 (GPR119) has been a promising target for the treatment of type 2 diabetes. It can not only directly promote insulin secretion, but also indirectly increase insulin secretion by stimulating the release of glucose-dependent GIP/CLP-1 without causing hypoglycemia. The remarkable advantages of small molecule GPR119 agonists make it one of the research hotspots for the development of type 2 diabetes drugs. This article reviews the anti-diabetic small molecules based on the GPR119 target in the past five years.
ABSTRACT
Aim To elucidate the effect of Lucy-tag polypeptide label on the expression of olfactory receptor membrane in sea lamprey ( Petromyzon marinus). Methods Immunocytochemis-try, double luciferase system and calcium flow detection were used to verify the effect of polypeptide label Lucy-tag on olfactory receptors of sea lamprey. Results Polypeptide label Lucy-tag promoted the membrane expression of 13 olfactory receptors out of 20 olfactory receptors, and Lucy-tag did not affect the intrinsic activity of olfactory receptors, nor did it affect the IP3 signaling pathway of G protein coupled receptor (GPCR). Conclusions It provides a favorable technique for finding the ligand of olfactory receptor and lays a good theoretical foundation for the further study of the function of the GPCR and ligand.
ABSTRACT
While several hypotheses about the neural mechanisms underlying auditory verbal hallucinations (AVH) have been suggested, the exact role of the recently highlighted intrinsic resting state activity of the brain remains unclear. Based on recent findings, we therefore developed what we call the 'resting state hypotheses' of AVH. Our hypothesis suggest that AVH may be traced back to abnormally elevated resting state activity in auditory cortex itself, abnormal modulation of the auditory cortex by anterior cortical midline regions as part of the default-mode network, and neural confusion between auditory cortical resting state changes and stimulus-induced activity. We discuss evidence in favour of our 'resting state hypothesis' and show its correspondence with phenomenal, i.e., subjective-experiential features as explored in phenomenological accounts. Therefore I speak of a 'neurophenomenal resting state hypothesis' of auditory hallucinations in schizophrenia.
Subject(s)
Auditory Cortex , Brain , Hallucinations , SchizophreniaABSTRACT
Objective To study the mechanism of insulin-stimulated glucose uptake in skeletal muscle cells. Methods The responses of GluT4 translocation and glucose uptake to the investigational drugs of SB203580 and Wortmannin as well as the effect of insulin on the drugs during differentiation were detected to study the insulin signal pathway. Results The GluT4 translocation and glucose transport were increased under insulin stimulation by 2.5±0.2 and 2.2±0.1 folds, respectively while compared with control; but t1/2 were 3.3 min and 6.0 min, and IC50 to wortmannin were 43 nmol/L and 3 nmol/L respectively.SB203580 inhibited 64% and 62% of insulin-stimulated glucose uptake and photolabelling of cell surface GluT4, respectively, but had no effect on GluT4 translocation.The fold increase of insulin-stimulated glucose uptake (1.7±0.1 fold vs control)was lower than that of GluT4 translocation (2.3±0.1 fold vs control) in myoblasts. Conclusions In skeletal muscle cells, two insulin signal pathways mediate GluT4 translocation and activation of GluT4, respectively.Insulin engages both of the pathways to stimulate the cells for maximum glucose uptake.