Insulinotropic effects of GPR120 agonists are altered in obese diabetic and obese non-diabetic states

2017 ◽  
Vol 131 (3) ◽  
pp. 247-260 ◽  
Author(s):  
Dan Zhang ◽  
Wing Yan So ◽  
Yi Wang ◽  
Shang Ying Wu ◽  
Qianni Cheng ◽  
...  
Keyword(s):  
G Protein ◽  
Peroxisome Proliferator ◽  
G Protein Coupled Receptor ◽  
Β Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
G Protein Coupled

Resident G-protein-coupled receptor 120 (GPR120) activation exhibits insulinotropic effects in rodent islets and β-cells. GPR120 expression in β-cells and insulinotropic effects of GPR120 activation are changed in differential ways in obese non-diabetic (OND) and diabetic states. Peroxisome proliferator-activated receptor γ (PPARγ) may facilitate these alterations.

scholarly journals Peroxisome Proliferator-activated Receptor γ Regulates Expression of the Anti-lipolytic G-protein-coupled Receptor 81 (GPR81/Gpr81)

2009 ◽  
Vol 284 (39) ◽  
pp. 26385-26393 ◽  
Author(s):  
Ellen H. Jeninga ◽  
Anne Bugge ◽  
Ronni Nielsen ◽  
Sander Kersten ◽  
Nicole Hamers ◽  
...  
Keyword(s):  
G Protein ◽  
Peroxisome Proliferator ◽  
G Protein Coupled Receptor ◽  
Peroxisome Proliferator Activated Receptor ◽  
G Protein Coupled

scholarly journals G Protein-coupled Receptor 40 (GPR40) and Peroxisome Proliferator-activated Receptor γ (PPARγ)

2015 ◽  
Vol 290 (32) ◽  
pp. 19544-19557 ◽  
Author(s):  
Shuibang Wang ◽  
Keytam S. Awad ◽  
Jason M. Elinoff ◽  
Edward J. Dougherty ◽  
Gabriela A. Ferreyra ◽  
...  
Keyword(s):  
G Protein ◽  
Peroxisome Proliferator ◽  
G Protein Coupled Receptor ◽  
Peroxisome Proliferator Activated Receptor ◽  
G Protein Coupled

scholarly journals G protein-coupled receptor 119 agonist DS-8500a effects on pancreatic β-cells in Japanese type 2 diabetes mellitus patients

2018 ◽  
Vol 10 (1) ◽  
pp. 84-93 ◽  
Author(s):  
Hirotaka Watada ◽  
Masanari Shiramoto ◽  
Shin Irie ◽  
Yasuo Terauchi ◽  
Yuichiro Yamada ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
G Protein Coupled

G-protein coupled receptor 55 agonists increase insulin secretion through inositol trisphosphate-mediated calcium release in pancreatic β-cells

2019 ◽  
Vol 854 ◽  
pp. 372-379 ◽  
Author(s):  
Chi Teng Vong ◽  
Hisa Hui Ling Tseng ◽  
Yiu Wa Kwan ◽  
Simon Ming-Yuen Lee ◽  
Maggie Pui Man Hoi
Keyword(s):  
Insulin Secretion ◽  
G Protein ◽  
Calcium Release ◽  
Inositol Trisphosphate ◽  
G Protein Coupled Receptor ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Increase Insulin Secretion ◽  
G Protein Coupled

scholarly journals Evidence for Osteocalcin Binding and Activation of GPRC6A in β-Cells

Endocrinology ◽  
2016 ◽  
Vol 157 (5) ◽  
pp. 1866-1880 ◽  
Author(s):  
Min Pi ◽  
Karan Kapoor ◽  
Ruisong Ye ◽  
Satoru Kenneth Nishimoto ◽  
Jeremy C. Smith ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
G Protein ◽  
Computational Models ◽  
Transmembrane Domain ◽  
Structural Basis ◽  
G Protein Coupled Receptor ◽  
Β Cells ◽  
Β Cell ◽  
Cell Functions ◽  
G Protein Coupled

Abstract The possibility that G protein-coupled receptor family C member A (GPRC6A) is the osteocalcin (Ocn)-sensing G protein-coupled receptor that directly regulates pancreatic β-cell functions is controversial. In the current study, we found that Ocn and an Ocn-derived C-terminal hexapeptide directly activate GPRC6A-dependent ERK signaling in vitro. Computational models probe the structural basis of Ocn binding to GPRC6A and predict that the C-terminal hexapeptide docks to the extracellular side of the transmembrane domain of GPRC6A. Consistent with the modeling, mutations in the computationally identified binding pocket of GPRC6A reduced Ocn and C-terminal hexapeptide activation of this receptor. In addition, selective deletion of Gprc6a in β-cells (Gprc6aβ-cell-cko) by crossing Gprc6aflox/flox mice with Ins2-Cre mice resulted in reduced pancreatic weight, islet number, insulin protein content, and insulin message expression. Both islet size and β-cell proliferation were reduced in Gprc6aβ-cell-cko compared with control mice. Gprc6aβ-cell-cko exhibited abnormal glucose tolerance, but normal insulin sensitivity. Islets isolated from Gprc6aβ-cell-cko mice showed reduced insulin simulation index in response to Ocn. These data establish the structural basis for Ocn direct activation of GPRC6A and confirm a role for GPRC6A in regulating β-cell proliferation and insulin secretion.

scholarly journals Role of the G-Protein Coupled Receptor 3-Salt Inducible Kinase 2 Pathway in Human β Cell Proliferation

2021 ◽  
Author(s):  
Caterina Iorio ◽  
Jillian L Rourke ◽  
Lisa Wells ◽  
Jun-Ichi Sakamaki ◽  
Emily Moon ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
G Protein ◽  
Cell Mass ◽  
Standard Of Care ◽  
G Protein Coupled Receptor ◽  
Β Cells ◽  
Β Cell ◽  
Cell Therapies ◽  
G Protein Coupled

Loss of pancreatic β cells is the hallmark of type 1 diabetes (T1D), for which provision of insulin is the standard of care. While regenerative and stem cell therapies hold the promise of generating single-source or host-matched tissue to obviate immune-mediated complications, these will still require surgical intervention and immunosuppression. Thus, methods that harness the innate capacity of β cells to proliferate to increase β cell mass in vivo are considered vital for future T1D treatment. However, early in life β cells enter what appears to be a permanent state of quiescence, directed by an evolutionarily selected genetic program that establishes a β cell mass setpoint to guard against development of fatal endocrine tumours. Here we report the development of a high-throughput RNAi screening approach to identify upstream pathways that regulate adult human β cell quiescence and demonstrate in a screen of the GPCRome that silencing G-protein coupled receptor 3 (GPR3) leads to human pancreatic β cell proliferation. Loss of GPR3 leads to activation of Salt Inducible Kinase 2 (SIK2), which is necessary and sufficient to drive cell cycle entry, increase β cell mass, and enhance insulin secretion in mice. Taken together, targeting the GPR3-SIK2 pathway represents a novel avenue to stimulate the regeneration of β cells.

scholarly journals Complement 1q-like-3 protein inhibits insulin secretion from pancreatic β-cells via the cell adhesion G protein–coupled receptor BAI3

2018 ◽  
Vol 293 (47) ◽  
pp. 18086-18098 ◽  
Author(s):  
Rajesh Gupta ◽  
Dan C. Nguyen ◽  
Michael D. Schaid ◽  
Xia Lei ◽  
Appakalai N. Balamurugan ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Insulin Secretion ◽  
G Protein ◽  
Human Islets ◽  
Whole Body ◽  
Inhibitory Effects ◽  
G Protein Coupled Receptor ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
G Protein Coupled

Secreted proteins are important metabolic regulators in both healthy and disease states. Here, we sought to investigate the mechanism by which the secreted protein complement 1q-like-3 (C1ql3) regulates insulin secretion from pancreatic β-cells, a key process affecting whole-body glucose metabolism. We found that C1ql3 predominantly inhibits exendin-4– and cAMP-stimulated insulin secretion from mouse and human islets. However, to a lesser extent, C1ql3 also reduced insulin secretion in response to KCl, the potassium channel blocker tolbutamide, and high glucose. Strikingly, C1ql3 did not affect insulin secretion stimulated by fatty acids, amino acids, or mitochondrial metabolites, either at low or submaximal glucose concentrations. Additionally, C1ql3 inhibited glucose-stimulated cAMP levels, and insulin secretion stimulated by exchange protein directly activated by cAMP-2 and protein kinase A. These results suggest that C1ql3 inhibits insulin secretion primarily by regulating cAMP signaling. The cell adhesion G protein–coupled receptor, brain angiogenesis inhibitor-3 (BAI3), is a C1ql3 receptor and is expressed in β-cells and in mouse and human islets, but its function in β-cells remained unknown. We found that siRNA-mediated Bai3 knockdown in INS1(832/13) cells increased glucose-stimulated insulin secretion. Furthermore, incubating the soluble C1ql3-binding fragment of the BAI3 protein completely blocked the inhibitory effects of C1ql3 on insulin secretion in response to cAMP. This suggests that BAI3 mediates the inhibitory effects of C1ql3 on insulin secretion from pancreatic β-cells. These findings demonstrate a novel regulatory mechanism by which C1ql3/BAI3 signaling causes an impairment of insulin secretion from β-cells, possibly contributing to the progression of type 2 diabetes in obesity.

Stearidonic acid promotes insulin secretion via stimulation of G protein-coupled receptor 40 in MIN6 pancreatic β-cells

2019 ◽  
Vol 60 ◽  
pp. 103450
Author(s):  
Yi-Xiong Gao ◽  
Cuihong Fan ◽  
Xin Tan ◽  
Jian Zhang ◽  
Jingzhong Wang
Keyword(s):  
Insulin Secretion ◽  
G Protein ◽  
Stearidonic Acid ◽  
G Protein Coupled Receptor ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
G Protein Coupled ◽  
Stimulation Of
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