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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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Description: Recombinant Human Interleukin 8 expressed in: E.coli

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Description: Recombinant Sheep Interleukin 8 expressed in: E.coli

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Description: Recombinant Pig Interleukin 8 expressed in: E.coli

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Description: Recombinant Simian Interleukin 8 expressed in: E.coli

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Recombinant Interleukin 8 (IL8)

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EUR 495

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EUR 428.5

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EUR 428.5

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  • EUR 927.60
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370068
  • EUR 2397.60
  • EUR 1513.20
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370095
  • EUR 1446.00
  • EUR 944.40
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370128
  • EUR 2047.20
  • EUR 1312.80
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370248
  • EUR 1412.40
  • EUR 927.60
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370249
  • EUR 1796.40
  • EUR 1161.60
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370251
  • EUR 1846.80
  • EUR 1195.20
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370256
  • EUR 2148.00
  • EUR 1362.00
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370625
  • EUR 1713.60
  • EUR 1111.20
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370655
  • EUR 2298.00
  • EUR 1462.80
  • 10 × 96 tests
  • 5 × 96 tests

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-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

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 (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 (CXCL8) Antibody

abx200558-100ug 100 ug
EUR 543.6

Interleukin 8 / IL8 (CXCL8) Antibody

20-abx210112
  • EUR 526.80
  • EUR 393.60
  • 100 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

Interleukin 8 / IL8 (CXCL8) Antibody

20-abx113257
  • EUR 878.40
  • EUR 477.60
  • 150 ul
  • 50 ul

Interleukin 8 / IL8 (CXCL8) Antibody

abx034024-400ul 400 ul
EUR 627.6

Interleukin 8 / IL8 (CXCL8) Antibody

abx034024-80l 80 µl
EUR 343.2

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

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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