ライフサイエンスコーパス: GLP1R

1 GLP1R agonists (GLP1RA) are widely used in the treatment

2 GLP1R agonists and DPP4 inhibitors might also attenuate

3 GLP1R is highly expressed on pancreatic beta-cells, and

4 GLP1R signaling can additionally be evoked when the rece

5 GLP1R-KD and CTRL rats displayed similar home cage food

6 hypophagic response to systemic Exendin-4, a GLP1R agonist that crosses the blood-brain barrier.

7 Importantly, as a GLP1R interactor, ATP6ap2 was required for GLP1-induced

8 LP1R bound to the peptide Exendin-4 (Exe4; a GLP1R agonist on the market for treating diabetes) using

9 tic kidney disease will test the effect of a GLP1R agonist on a primary kidney disease outcome.

10 study, adolescents with obesity prescribed a GLP1R had a lower incidence of suicidal ideation or atte

11 that are distinct from those obtained with a GLP1R-selective agonist.

12 tematic investigation across drug-accessible GLP1R populations revealed that only hindbrain neurons a

13 We examined whether a long acting GLP1R/GCGR dual agonist peptide exerts metabolic effects

14 then administered liraglutide, a long-acting GLP1R agonist.

15 body weight-lowering effects of long-acting GLP1R agonists are via direct action on CNS GLP1R or the

16 ver, their function is dependent on adequate GLP1R expression, which is downregulated in diabetes.

17 Glucagon-like peptide 1 receptor agonists (GLP1R) are increasingly being used for the treatment of

18 Although GLP1R knockout (GLP1RKO) and wild-type (WT) mice exhibit

19 it also enhanced islet GLP1R expression and GLP1R agonist-induced insulin secretion and glucose tole

20 GDNF-family receptor alpha-like (GFRAL) and GLP1R, to reduce food intake and body weight.

21 the suppression of food intake by leptin and GLP1R agonists.

22 is of obesity and evidence of an antiobesity GLP1R prescription or lifestyle intervention without GLP

23 ral analyses revealed that NTS(GLP1R) and AP(GLP1R) neurons send projections to different downstream

24 bsence of aversion, whereas activation of AP(GLP1R) neurons triggers strong aversion with food intake

25 subregions indicated that area postrema (AP) GLP1R neurons are broadly responsive, whereas nucleus of

26 Presently commercially available GLP1R agonists are peptides that limit their use due to

27 vel dual role in beta cells, modulating both GLP1R signaling and insulin processing to affect insulin

28 effects of DualAG require activation of both GLP1R and GCGR.

29 l sympathetic overactivity were abolished by GLP1R activation in the CB suggesting a role in a homeos

30 islet, brain and hESC-derived beta-like cell GLP1R expression patterns, reveal higher-order GLP1R org

31 and ATP6ap2 were co-expressed in beta cells, GLP1R was shown to directly interact with ATP6ap2, as as

32 erone (cort) levels in rats, whereas central GLP1R antagonism has opposite effects.

33 GLP1R agonists are via direct action on CNS GLP1R or the result of downstream activation of afferent

34 1R/GCGR agonist, DualAG, and a corresponding GLP1R-selective agonist, GLPAG, matched for GLP1R agonis

35 We demonstrate GLP1R to be localized to CB chemosensory cells, while ta

36 We discovered GLP1R (glucagon-like peptide-1 receptor) expression in t

37 N AND We developed a protease-resistant dual GLP1R/GCGR agonist, DualAG, and a corresponding GLP1R-se

38 xendin4 concentration in the pancreas (i.e., GLP1R density) correlated inversely with the age of the

39 ing probes allow visualization of endogenous GLP1R, and provide insight into class B GPCR distributio

40 these technologies, we show that endogenous GLP1R can be specifically and sensitively detected in pr

41 n neurons within alBST subregions expressing GLP1R.

42 e present LUXendin645, a far-red fluorescent GLP1R antagonistic peptide label.

43 GLP1R-selective agonist, GLPAG, matched for GLP1R agonist potency and pharmacokinetics.

44 ellular composition, highlighting key genes (GLP1R, PLIN4, and KLF10) and cell-type differences betwe

45 Overall, higher genetic GLP1R gene expression was associated with a lower risk o

46 cribe a separate pathway downstream of GFRAL/GLP1R neurons that involves a distinct population of bra

47 t the inclusion of GIPR agonism in dual GIPR/GLP1R agonists could potentiate the protective effect of

48 l identity, such as downregulation of GLUT2, GLP1R, and MafA, and in vitro knockdown of GLUT2 in beta

49 In this genetic association study, higher GLP1R gene expression was associated with a small reduct

50 In vivo two-photon imaging of hindbrain GLP1R neurons demonstrated that most neurons are tuned t

51 enes involved in plasma glucose homeostasis (GLP1R) and lipid metabolism as well as maternal-fetal li

52 However, GLP1R is a member of the class B1 family of GPCRs for wh

53 ted green fluorescent protein into the human GLP1R, named GLPLight1.

54 These findings identify GLP1R as a novel regulator of allogeneic HSC engraftment

55 Importantly, GLP1R agonists reduce food intake even when the aversion

56 baseline plasma cort levels were similar in GLP1R-KD and CTRL rats, GLP1R-KD rats displayed a prolon

57 tion of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (beta=

58 pe 2 diabetes, nor with missense variants in GLP1R.

59 le binding with GLP1R ectodomain and induces GLP1R internalization and increasing cAMP levels.

60 cal distension of the stomach and intestine (GLP1R neurons).

61 further studies are warranted to investigate GLP1R-directed therapies in the context of allogeneic HS

62 Indeed, it also enhanced islet GLP1R expression and GLP1R agonist-induced insulin secre

63 , in vivo deletion of miR-204 promoted islet GLP1R expression and enhanced responsiveness to GLP1R ag

64 in both chow- and high-fat-fed mice lacking GLP1R in the CNS or visceral nerves; however, liraglutid

65 At the nanoscopic level, GLP1Rs are found to possess higher organization, undergo

66 ( d) MnPO(GLP1R) neurons serve as a central detector that discrimi

67 ompared with previously known small molecule GLP1R agonists.

68 to knock down the translation of GLP1R mRNA (GLP1R-KD rats), or similar injections of a control AAV (

69 f downstream activation of afferent neuronal GLP1R.

70 oned taste aversion in mice lacking neuronal GLP1R.

71 These data indicate that neuronal GLP1Rs mediate body weight and anorectic effects of lira

72 esity who were prescribed semaglutide or non-GLP1R agonist anti-obesity medications, with the finding

73 utide with suicidal ideation compared to non-GLP1R agonist anti-obesity or anti-diabetes medications.

74 72.6% female), semaglutide compared with non-GLP1R agonist anti-obesity medications was associated wi

75 ideation with semaglutide compared with non-GLP1R agonist anti-obesity or anti-diabetes medications.

76 lecule, PK2, as an orally active nonpeptidic GLP1R agonist that has efficacy to preserve or restore f

77 in yeast two-hybrid assays to identify novel GLP1R interactors in both mouse and human islets.

78 Overall, these findings highlight NTS(GLP1R) neurons as a population that could be selectively

79 ulations demonstrated that activation of NTS(GLP1R) neurons triggers satiety in the absence of aversi

80 l and behavioural analyses revealed that NTS(GLP1R) and AP(GLP1R) neurons send projections to differe

81 whereas nucleus of the solitary tract (NTS) GLP1R neurons are biased towards nutritive stimuli.

82 ovide fresh insights into sites of action of GLP1R agonists and a strategy to help promote weight gai

83 ng ligand binding and receptor activation of GLP1R and other class B1 GPCRs.

84 sory cells, while targeted administration of GLP1R agonist to the CB lowered its basal discharge and

85 Longitudinal analysis of GLP1R dynamics reveals heterogeneous recruitment of neig

86 There was no evidence of self-blocking of GLP1R by the tracer in this protocol, despite the high p

87 e enabled delineation of the contribution of GLP1R versus GCGR activation to the pharmacology of Dual

88 -GLP1) and to demonstrate optical control of GLP1R activation.

89 g protocol to enable reproducible imaging of GLP1R in the pancreas.

90 objective was to use a method independent of GLP1R antibodies to identify and characterize the target

91 e have confirmed the remarkable potential of GLP1R agonist conjugation for the delivery of ASOs to pa

92 Initial prescription of GLP1R (study cohort) or lifestyle intervention without G

93 Prescription of GLP1R was associated with a 33% reduced risk for suicida

94 st a favorable psychiatric safety profile of GLP1R in adolescents.

95 We found that neither reduction of GLP1R in the CNS nor in the visceral nerves resulted in

96 To examine the functional role of GLP1R signaling within the alBST, adult male Sprague Daw

97 tion studies and scoping of a diverse set of GLP1R agonists proved fruitful to identify additional ta

98 d the transmembrane (TM) bundle structure of GLP1R bound to the peptide Exendin-4 (Exe4; a GLP1R agon

99 potential to enable longitudinal studies of GLP1R in the human pancreas.

100 The activation and transduction of GLP1R requires complex interactions with a host of acces

101 RNA (shRNA) to knock down the translation of GLP1R mRNA (GLP1R-KD rats), or similar injections of a c

102 RNA, miR-204, directly targets the 3' UTR of GLP1R and thereby downregulates its expression in the be

103 tinct sets of small molecules were docked on GLP1R ectodomain and compared with previously known smal

104 ls, and activation by endogenous incretin or GLP1R agonists increases cAMP generation, which stimulat

105 P1R expression patterns, reveal higher-order GLP1R organization including membrane nanodomains, and t

106 cation of longitudinal changes in pancreatic GLP1R during the development of type 2 diabetes, as well

107 ompared with matched patients not prescribed GLP1R who were treated with lifestyle intervention.

108 on among adolescents with obesity prescribed GLP1R suggests potential avenues for future research.

109 vels were similar in GLP1R-KD and CTRL rats, GLP1R-KD rats displayed a prolonged stress-induced eleva

110 Compared with CTRL rats, GLP1R-KD rats gained more body weight over time and disp

111 eatment, a glucagon-like peptide 1 receptor (GLP1R) agonist medication for type 2 diabetes (T2DM) and

112 jugated to Glucagon Like Peptide 1 Receptor (GLP1R) agonist peptide ligands.

113 ch include glucagon-like peptide 1 receptor (GLP1R) agonists and dipeptidyl peptidase 4 (DPP4) inhibi

114 Glucagon-like peptide 1 receptor (GLP1R) agonists are widely used to treat diabetes.

115 Glucagon-like-peptide-1 receptor (GLP1R) agonists have been the focus of considerable rese

116 rapeutics, glucagon-like peptide-1 receptor (GLP1R) agonists, cause aversive responses such as nausea

117 ighted the glucagon-like peptide-1 receptor (GLP1R) as a critical regulator of immune homeostasis, ye

118 The glucagon-like peptide-1 receptor (GLP1R) is a broadly expressed target of peptide hormones

119 The glucagon-like peptide-1 receptor (GLP1R) is a class B G protein-coupled receptor (GPCR) in

120 The glucagon-like peptide-1 receptor (GLP1R) is a class B G protein-coupled receptor (GPCR) in

121 The glucagon-like peptide 1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) involved i

122 The glucagonlike peptide-1 receptor (GLP1R) is a gut hormone receptor, intricately linked to

123 ng which tissues express the GLP-1 receptor (GLP1R) is critical for the development of GLP-1-based th

124 ariants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that

125 ompetitive antagonist of the GLP-1 Receptor (GLP1R), was infused, while on the other, saline was infu

126 a glucagon-like peptide 1 (GLP-1) receptor (GLP1R)/glucagon receptor (GCGR) dual agonist peptide tha

127 ffects and malaise induced by GLP1 receptor (GLP1R) analogs, suggesting that MC3R antagonists or MC4R

128 the glucagon-like peptide 1 (GLP1) receptor (GLP1R) on beta cells.

129 GLP1 activates its receptor, GLP1R, to enhance insulin secretion.

130 GCGR) and glucagon-like peptide-1 receptors (GLP1R), demonstrating a more dynamic range of effects th

131 by the brain, which contains GLP1 receptors (GLP1R).

132 expresses glucagon-like peptide-1 receptors (GLP1Rs) and receives input from caudal brainstem GLP1 ne

133 ic acinar cells (GP2) and insulin secretion (GLP1R).

134 ntroduced here enhances our ability to study GLP1R activation with high spatiotemporal resolution.

135 Sustained GLP1R/GCGR dual agonism reverses obesity in DIO mice and

136 Genetic risk score for systemic GLP1R gene expression that was calculated for each study

137 We conclude that GLP1R expressed within the alBST contributes to multiple

138 nd quantitative real-time PCR confirmed that GLP1R-KD rats displayed a significant 60% reduction in t

139 Here, we demonstrated that GLP1R deficiency in recipient mice leads to a profound i

140 In situ hybridization revealed that GLP1R mRNA is expressed in a subset of GABAergic alBST n

141 allogeneic HSC engraftment and suggest that GLP1R agonists, widely used for metabolic disorders, may

142 present studies show for the first time that GLP1R is under the control of a microRNA, miR-204, and u

143 mice enabled food intake suppression by the GLP1R agonist, liraglutide.

144 obesity intervention were identified for the GLP1R cohort and 50 112 were identified for the control

145 y a group of proteins that interact with the GLP1R.

146 cts of OXM have been attributed primarily to GLP1R agonism.

147 1R expression and enhanced responsiveness to GLP1R agonists, resulting in improved glucose tolerance,

148 Similar to GLP1R peptidic agonists, treatment of PK2 induces beta-c

149 However, the total GLP1R content in the pancreas did not.

150 a significant 60% reduction in translatable GLP1R mRNA.

151 orating excessive sympathetic activity using GLP1R agonists in the hypertensive-diabetic condition.

152 When GLP1R and ATP6ap2 were co-expressed in beta cells, GLP1R

153 It is currently unknown whether GLP1R treatment is associated with suicidal ideation or

154 KO mice, further supporting a model in which GLP1R signaling restrains host lymphocyte-mediated graft

155 nt based on genetic variants associated with GLP1R mRNA levels across all tissue samples within the G

156 -b]quinoxaline) displays stable binding with GLP1R ectodomain and induces GLP1R internalization and i

157 nd 14 strong polar interactions of Exe4 with GLP1R, of which 8 interactions are in the TM bundle (2 i

158 nown whether DYRK1A inhibitors together with GLP1R agonists (GLP1RAs) affect human beta cell survival

159 dy cohort) or lifestyle intervention without GLP1R (control cohort).

160 escription or lifestyle intervention without GLP1R within the following year.