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Inhibition of the prostaglandin D2-GPR44/DP2 axis improves human islet survival and function.

Inhibition of the prostaglandin D2-GPR44/DP2 axis improves human islet survival and function.
Posted by Frank

AIMS / HYPOTHESIS
inflammatory signals and increase the synthesis of prostaglandins play a role during the development of diabetes. The prostaglandin D2 (PGD2) receptor, GPR44 / DP2, is highly expressed in human islets and insulin secretion pathway activation results impaired. GPR44 activation role in the function of small islands and the survival rate for chronic hyperglycaemic conditions are unknown. In this study, we investigated GPR44 GPR44 inhibition by using a selective antagonist (AZ8154) in humans the island both in vitro and in vivo in diabetic mice transplanted with human islets.


METHOD
human islets exposed to PGD2 or proinflammatory cytokines in vitro to determine the effect of GPR44 inhibition on the survival rate of the island. In addition, the molecular mechanism of inhibition of GPR44 investigated in human islets exposed to high concentrations of glucose (HG) and IL-1β.

To the in vivo from this study, human islets are transplanted under the kidney capsule of diabetic rats immunodeficiencies and treated with 6, 60 or 100 mg / kg per day antagonist of GPR44 from the day of transplantation until day 4 short-term (studies) or study days (term long-17) post transplant. IVGTT conducted in rats at 10 days 15 days post transplant. After the termination of the study, metabolic variables, human circulating proinflammatory cytokines, and hepatocyte growth factor (HGF) were analyzed in human islets transplanted.


RESULTS
PGD2 or proinflammatory cytokine-induced apoptosis in human islets, while GPR44 inhibition of reverse these effects. GPR44 inhibition of hate decreased insulin secretion induced by glucose-stimulated HG and IL-1β in human islets. It is accompanied by activation of glycogen synthase kinase-Akt signaling 3β together with the phosphorylation and inactivation of the forkhead box O-1 and upregulation of pancreatic and duodenal homeobox-1 and HGF.

GPR44 antagonist administration up to 17 days for the diabetic mice transplanted with human islets resulted in a marginal reduction in fasting blood glucose and lower glucose fluctuations during IVGTT. improved glucose regulation is supported by an increased level of human C-peptide compared to the vehicle group on day 4 and throughout the treatment period. GPR44 inhibition reduces plasma levels of TNF-α and growth-regulated oncogene-α / chemokine (C-X-C motif) ligand 1 and raise the level of HGF in human islets.


Inhibition of GPR44 in human islets have the potential to improve the functioning of small islands and the survival rate under pressure inflammation and hyperglycaemic. This may have implications for the survival rates were better than the island after transplantation.

Inhibition of the prostaglandin D2-GPR44/DP2 axis improves human islet survival and function.
Inhibition of the prostaglandin D2-GPR44/DP2 axis improves human islet survival and function.

1 Channel Control Pannexin endothelial inflammation by regulating intracellular calcium.

The proinflammatory cytokine IL-1β is a significant risk factor in cardiovascular disease that can be targeted to reduce major cardiovascular events. expression and release of IL-1β is tightly controlled by changes in intracellular Ca2 + ([Ca2 +] i), which has been associated with the release of ATP and purinergic signaling. However, the mechanisms that regulate these changes have not been identified.

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  • 1 mg
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  • 10 ug
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  • 10 ug
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  • 50 ug

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  • 1 mg
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  • 20 ug
  • 50 ug

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  • EUR 1045.20
  • EUR 543.60
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  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

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  • EUR 360.00
  • EUR 844.80
  • EUR 427.20
  • EUR 184.80
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  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

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  • EUR 994.80
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  • EUR 184.80
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  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

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  • EUR 994.80
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  • EUR 184.80
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  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Interleukin 8 (IL8) Antibody

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  • EUR 159.60
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  • 10 ug
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  • 200 ug
  • 50 ug

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  • EUR 351.60
  • EUR 1155.60
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  • 100ug
  • 1MG
  • 200ug
  • 500ug
Description: Recombinant Dog Interleukin-8(IL8) expressed in Mammalian cell

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  • EUR 276.00
  • EUR 1813.44
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  • EUR 1248.96
  • EUR 458.40
  • EUR 4353.60
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Bovine Interleukin 8 expressed in: 293F cell

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  • EUR 700.61
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  • EUR 2297.28
  • EUR 845.76
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  • EUR 544.80
  • EUR 5563.20
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Human Interleukin 8 expressed in: Available from E.coli, Yeast, Baculovirus and Mammalian cells

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  • EUR 528.58
  • EUR 265.20
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  • EUR 1141.44
  • EUR 429.60
  • EUR 3950.40
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Dog Interleukin 8 expressed in: E.coli

Recombinant Interleukin 8 (IL8)

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  • EUR 603.84
  • EUR 285.60
  • EUR 1934.40
  • EUR 724.80
  • EUR 1329.60
  • EUR 480.00
  • EUR 4656.00
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Horse Interleukin 8 expressed in: E.coli

Recombinant Interleukin 8 (IL8)

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  • EUR 636.10
  • EUR 294.00
  • EUR 2055.36
  • EUR 765.12
  • EUR 1410.24
  • EUR 501.60
  • EUR 4958.40
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Chicken Interleukin 8 expressed in: E.coli

Recombinant Interleukin 8 (IL8)

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  • EUR 571.58
  • EUR 276.00
  • EUR 1813.44
  • EUR 684.48
  • EUR 1248.96
  • EUR 458.40
  • EUR 4353.60
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Guinea pig Interleukin 8 expressed in: E.coli

Recombinant Interleukin 8 (IL8)

4-RPA080Hu01
  • EUR 442.56
  • EUR 242.40
  • EUR 1329.60
  • EUR 523.20
  • EUR 926.40
  • EUR 372.00
  • EUR 3144.00
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Human Interleukin 8 expressed in: E.coli

Recombinant Interleukin 8 (IL8)

4-RPA080Ov01
  • EUR 657.60
  • EUR 300.00
  • EUR 2136.00
  • EUR 792.00
  • EUR 1464.00
  • EUR 516.00
  • EUR 5160.00
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Sheep Interleukin 8 expressed in: E.coli

Recombinant Interleukin 8 (IL8)

4-RPA080Po01
  • EUR 636.10
  • EUR 294.00
  • EUR 2055.36
  • EUR 765.12
  • EUR 1410.24
  • EUR 501.60
  • EUR 4958.40
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Pig Interleukin 8 expressed in: E.coli

Recombinant Interleukin 8 (IL8)

4-RPA080Rb01
  • EUR 636.10
  • EUR 294.00
  • EUR 2055.36
  • EUR 765.12
  • EUR 1410.24
  • EUR 501.60
  • EUR 4958.40
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Rabbit Interleukin 8 expressed in: E.coli

Recombinant Interleukin 8 (IL8)

4-RPA080Si01
  • EUR 636.10
  • EUR 294.00
  • EUR 2055.36
  • EUR 765.12
  • EUR 1410.24
  • EUR 501.60
  • EUR 4958.40
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Simian Interleukin 8 expressed in: E.coli

Dog Interleukin-8 (IL8)

1-CSB-EP011671DO
  • EUR 733.20
  • EUR 370.80
  • EUR 2192.40
  • EUR 1126.80
  • EUR 1461.60
  • EUR 476.40
  • 100ug
  • 10ug
  • 1MG
  • 200ug
  • 500ug
  • 50ug
Description: Recombinant Dog Interleukin-8(IL8) expressed in E.coli

Sheep Interleukin-8 (IL8)

1-CSB-EP011671SH
  • EUR 733.20
  • EUR 370.80
  • EUR 2192.40
  • EUR 1126.80
  • EUR 1461.60
  • EUR 476.40
  • 100ug
  • 10ug
  • 1MG
  • 200ug
  • 500ug
  • 50ug
Description: Recombinant Sheep Interleukin-8(IL8) expressed in E.coli

Dog Interleukin-8 (IL8)

1-CSB-YP011671DO
  • EUR 814.80
  • EUR 402.00
  • EUR 2606.40
  • EUR 1261.20
  • EUR 1730.40
  • EUR 522.00
  • 100ug
  • 10ug
  • 1MG
  • 200ug
  • 500ug
  • 50ug
Description: Recombinant Dog Interleukin-8(IL8) expressed in Yeast

Interleukin 8 (IL8) Antibody

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  • EUR 427.20
  • EUR 627.60
  • 0.5 mg
  • 1 mg

Interleukin 8 (IL8) Antibody

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EUR 1296

Interleukin 8 (IL8) Antibody

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  • EUR 360.00
  • EUR 526.80
  • EUR 226.80
  • 100 ul
  • 200 ul
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Interleukin 8 (IL8) Antibody

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  • EUR 644.40
  • EUR 326.40
  • EUR 978.00
  • EUR 427.20
  • 100 tests
  • 200 tests
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  • 50 tests

Interleukin 8 (IL8) Antibody

20-abx270152
  • EUR 560.40
  • EUR 644.40
  • EUR 326.40
  • EUR 978.00
  • EUR 427.20
  • 100 tests
  • 200 tests
  • 25 tests
  • 500 tests
  • 50 tests

Interleukin 8 (IL8) Antibody

20-abx270200
  • EUR 560.40
  • EUR 644.40
  • EUR 326.40
  • EUR 978.00
  • EUR 427.20
  • 100 tests
  • 200 tests
  • 25 tests
  • 500 tests
  • 50 tests

Interleukin 8 (IL8) Antibody

20-abx270201
  • EUR 560.40
  • EUR 644.40
  • EUR 326.40
  • EUR 978.00
  • EUR 427.20
  • 100 tests
  • 200 tests
  • 25 tests
  • 500 tests
  • 50 tests

Interleukin 8 (IL8) Antibody

20-abx177201
  • EUR 1429.20
  • EUR 693.60
  • 1 mg
  • 200 ug

Interleukin 8 / IL8 (CXCL8) Antibody

20-abx210112
  • EUR 526.80
  • EUR 393.60
  • 100 ug
  • 50 ug

Interleukin 8 / IL8 (CXCL8) Antibody

20-abx100968
  • EUR 510.00
  • EUR 159.60
  • EUR 1412.40
  • EUR 693.60
  • EUR 393.60
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Interleukin 8 / IL8 (CXCL8) Antibody

20-abx109944
  • EUR 493.20
  • EUR 2214.00
  • EUR 718.80
  • EUR 218.40
  • EUR 360.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Interleukin 8 / IL8 (CXCL8) Antibody

20-abx110542
  • EUR 493.20
  • EUR 2214.00
  • EUR 718.80
  • EUR 218.40
  • EUR 360.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Interleukin 8 / IL8 (CXCL8) Antibody

20-abx110581
  • EUR 493.20
  • EUR 2214.00
  • EUR 718.80
  • EUR 218.40
  • EUR 360.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Dog Interleukin 8 (IL8) Protein

20-abx067553
  • EUR 744.00
  • EUR 326.40
  • EUR 2230.80
  • EUR 878.40
  • EUR 543.60
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Horse Interleukin 8 (IL8) Protein

20-abx067554
  • EUR 844.80
  • EUR 343.20
  • EUR 2598.00
  • EUR 994.80
  • EUR 594.00
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Chicken Interleukin 8 (IL8) Protein

20-abx067555
  • EUR 878.40
  • EUR 343.20
  • EUR 2766.00
  • EUR 1062.00
  • EUR 627.60
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Human Interleukin 8 (IL8) Protein

20-abx067557
  • EUR 627.60
  • EUR 292.80
  • EUR 1796.40
  • EUR 727.20
  • EUR 460.80
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Pig Interleukin 8 (IL8) Protein

20-abx067558
  • EUR 878.40
  • EUR 343.20
  • EUR 2766.00
  • EUR 1062.00
  • EUR 627.60
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Rabbit Interleukin 8 (IL8) Protein

20-abx067559
  • EUR 878.40
  • EUR 343.20
  • EUR 2766.00
  • EUR 1062.00
  • EUR 627.60
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Monkey Interleukin 8 (IL8) Protein

20-abx067560
  • EUR 878.40
  • EUR 343.20
  • EUR 2766.00
  • EUR 1062.00
  • EUR 627.60
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Sheep Interleukin 8 (IL8) Protein

20-abx067561
  • EUR 910.80
  • EUR 360.00
  • EUR 2865.60
  • EUR 1095.60
  • EUR 644.40
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Cow Interleukin 8 (IL8) Protein

20-abx654060
  • EUR 777.60
  • EUR 326.40
  • EUR 2397.60
  • EUR 927.60
  • EUR 560.40
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Goat Interleukin 8 (IL8) Protein

20-abx654061
  • EUR 777.60
  • EUR 326.40
  • EUR 2397.60
  • EUR 927.60
  • EUR 560.40
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Cow Interleukin 8 (IL8) Protein

20-abx651537
  • EUR 794.40
  • EUR 326.40
  • EUR 2448.00
  • EUR 944.40
  • EUR 577.20
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Interleukin 8 / IL8 (CXCL8) Antibody

20-abx317929
  • EUR 493.20
  • EUR 2214.00
  • EUR 718.80
  • EUR 218.40
  • EUR 360.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Interleukin 8 (IL8) Antibody (Biotin)

20-abx273442
  • EUR 560.40
  • EUR 292.80
  • EUR 1612.80
  • EUR 760.80
  • EUR 410.40
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Interleukin 8 (IL8) Antibody (Biotin)

20-abx273458
  • EUR 526.80
  • EUR 292.80
  • EUR 1513.20
  • EUR 727.20
  • EUR 410.40
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Interleukin 8 (IL8) Antibody (FITC)

20-abx273525
  • EUR 410.40
  • EUR 260.40
  • EUR 1161.60
  • EUR 577.20
  • EUR 343.20
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Interleukin 8 (IL8) Antibody (FITC)

20-abx273530
  • EUR 493.20
  • EUR 276.00
  • EUR 1395.60
  • EUR 678.00
  • EUR 376.80
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Interleukin 8 (IL8) Antibody (FITC)

20-abx273545
  • EUR 526.80
  • EUR 292.80
  • EUR 1496.40
  • EUR 727.20
  • EUR 393.60
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Interleukin 8 (IL8) Antibody (FITC)

20-abx273851
  • EUR 410.40
  • EUR 260.40
  • EUR 1178.40
  • EUR 594.00
  • EUR 343.20
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Interleukin 8 (IL8) Antibody (FITC)

20-abx274200
  • EUR 560.40
  • EUR 292.80
  • EUR 1646.40
  • EUR 777.60
  • EUR 427.20
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

The pannexin 1 (Panx1) channel has been canonically been involved in the ATP release, particularly during inflammation. We checked Panx1 in human umbilical vein endothelial cells after treatment with proinflammatory cytokines TNF-α. Analysis by the whole transcriptome sequencing and immunoblot Panx1 identified a dramatic increase in mRNA and protein expression were regulated by NF-kB-dependent.

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