Objective To investigate the neural basis of glucagon-like peptide-1(GLP-1)in regulating glucose homeostasis and elucidate the molecular mechanisms.Methods Male Glp1r-IRES-Cre,Glp1r-KO,and wild-type mice were used in this study.Fiber photometry was employed to record Ca2+signals of neurons in ventromedial hypothalamus(VMH)and patch-clamp was used to analyze electrophysiological properties of GLP-1 receptor-positive(GLP-1RVMH)neurons.Viral stereotaxic injections,chemogenetics,plasma hormone assays,and routine glucose metabolism assessments were combined to determine the regulatory role of GLP-1RVMH neurons in glucose homeostasis.Tissue and cell mitochondrial respiratory function assays,transmission electron microscopy,and conventional molecular biology methods were used to explore the mechanism by which GLP-1R agonists regulate glucose homeostasis.Results When the glucose concentration decreased from 5.0 mmol/L to 0.5 mmol/L,the action potential frequency of GLP-1RVMH neuron decreased significantly[(4.51±0.80)Hz vs.(1.43±0.51)Hz,P<0.01].Activation of GLP-1RVMH neuron significantly enhanced insulin secretion[(7.60±0.56)μU/mL vs.(11.34±0.93)μU/mL,P<0.01],while inhibition of these neuronal activities impaired the hypoglycemic efficiency of GLP-1 agonists[(32.03%±0.91%)vs.(25.77%±1.09%),P<0.001)].Mechanistically,GLP-1 regulated glucose homeostasis through Drp1 phosphorylation-mediated mitochondrial fission and improved mitochondrial energy metabolism.Conclusion GLP-1RVMH neurons are a class of glucose-excited neurons,and which activated directly promotes secretion of insulin.The hypoglycemic effect of GLP-1R agonists depend on the neuronal activity of GLP-1RVMH.

Objective To investigate the neural basis of glucagon-like peptide-1(GLP-1)in regulating glucose homeostasis and elucidate the molecular mechanisms.Methods Male Glp1r-IRES-Cre,Glp1r-KO,and wild-type mice were used in this study.Fiber photometry was employed to record Ca2+signals of neurons in ventromedial hypothalamus(VMH)and patch-clamp was used to analyze electrophysiological properties of GLP-1 receptor-positive(GLP-1RVMH)neurons.Viral stereotaxic injections,chemogenetics,plasma hormone assays,and routine glucose metabolism assessments were combined to determine the regulatory role of GLP-1RVMH neurons in glucose homeostasis.Tissue and cell mitochondrial respiratory function assays,transmission electron microscopy,and conventional molecular biology methods were used to explore the mechanism by which GLP-1R agonists regulate glucose homeostasis.Results When the glucose concentration decreased from 5.0 mmol/L to 0.5 mmol/L,the action potential frequency of GLP-1RVMH neuron decreased significantly[(4.51±0.80)Hz vs.(1.43±0.51)Hz,P<0.01].Activation of GLP-1RVMH neuron significantly enhanced insulin secretion[(7.60±0.56)μU/mL vs.(11.34±0.93)μU/mL,P<0.01],while inhibition of these neuronal activities impaired the hypoglycemic efficiency of GLP-1 agonists[(32.03%±0.91%)vs.(25.77%±1.09%),P<0.001)].Mechanistically,GLP-1 regulated glucose homeostasis through Drp1 phosphorylation-mediated mitochondrial fission and improved mitochondrial energy metabolism.Conclusion GLP-1RVMH neurons are a class of glucose-excited neurons,and which activated directly promotes secretion of insulin.The hypoglycemic effect of GLP-1R agonists depend on the neuronal activity of GLP-1RVMH.

Objective To investigate how opioid-free anesthesia affects the occurrence of emergence agitation(EA)during recovery after transurethral resection of prostate(TURP).Methods A total of 78 patients undergoing TURP from May 2023 to June 2024 in the First People's Hospital of Huzhou were selected as the study subjects.Patients were assigned to two groups using a random number table method,group F received fentanyl(3μg/kg)+propofol(2mg/kg),and group LY received esketamine(0.3mg/kg)+propofol(2mg/kg),39 cases in each group.EA was assessed every 5 minutes following the removal of the laryngeal mask,and pain levels were measured using the visual analog score(VAS).Mean arterial pressure(MAP)and heart rate(HR)were recorded at admission(T0),immediately after laryngeal mask insertion(T1),3 minutes after(T2),6 minutes after(T3),and 9 minutes after(T4).Data on rescue analgesia,operation time,recovery time,and adverse reactions during recovery,such as agitation,nausea,vomiting,hypoxemia,nightmares,and hallucinations were also recorded.Results Compared to group F,incidence of postoperative EA,highest VAS score,and extubation time in group LY were lower(P＜0.05).The highest sedation score in group LY was greater than that in group F(P＜0.05).The comparison of HR and MAP at each time point between two groups showed statistically significant differences from T1 to T4(P＜0.05).Conclusion The opioid-free anesthesia regimen reduces incidence of EA and postoperative pain scores in TURP patients without increasing adverse reactions during recovery.

Objective To investigate how opioid-free anesthesia affects the occurrence of emergence agitation(EA)during recovery after transurethral resection of prostate(TURP).Methods A total of 78 patients undergoing TURP from May 2023 to June 2024 in the First People's Hospital of Huzhou were selected as the study subjects.Patients were assigned to two groups using a random number table method,group F received fentanyl(3μg/kg)+propofol(2mg/kg),and group LY received esketamine(0.3mg/kg)+propofol(2mg/kg),39 cases in each group.EA was assessed every 5 minutes following the removal of the laryngeal mask,and pain levels were measured using the visual analog score(VAS).Mean arterial pressure(MAP)and heart rate(HR)were recorded at admission(T0),immediately after laryngeal mask insertion(T1),3 minutes after(T2),6 minutes after(T3),and 9 minutes after(T4).Data on rescue analgesia,operation time,recovery time,and adverse reactions during recovery,such as agitation,nausea,vomiting,hypoxemia,nightmares,and hallucinations were also recorded.Results Compared to group F,incidence of postoperative EA,highest VAS score,and extubation time in group LY were lower(P＜0.05).The highest sedation score in group LY was greater than that in group F(P＜0.05).The comparison of HR and MAP at each time point between two groups showed statistically significant differences from T1 to T4(P＜0.05).Conclusion The opioid-free anesthesia regimen reduces incidence of EA and postoperative pain scores in TURP patients without increasing adverse reactions during recovery.