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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 Guinea pig Interleukin 8 expressed in: E.coli

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

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  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
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Description: Recombinant Pig Interleukin 8 expressed in: E.coli

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  • 200ug
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  • 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 3628.00
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  • 10ug
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  • 200 ug
  • 500 ug
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  • 5 mg
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  • EUR 453.00
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  • 100 ug
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  • EUR 1316.00
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  • EUR 1372.00
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  • 50 ug

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  • EUR 467.00
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  • 100 ug
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  • 20 ug
  • 50 ug

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  • EUR 871.00
  • EUR 453.00
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  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Interleukin 8 (IL8) Antibody

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  • EUR 328.00
  • EUR 829.00
  • EUR 425.00
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  • EUR 258.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

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  • EUR 843.00
  • EUR 439.00
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  • EUR 258.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Interleukin 8 (IL8) Antibody

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  • EUR 342.00
  • EUR 871.00
  • EUR 453.00
  • EUR 154.00
  • EUR 272.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

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  • EUR 342.00
  • EUR 871.00
  • EUR 453.00
  • EUR 154.00
  • EUR 272.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Interleukin 8 (IL8) Antibody

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  • EUR 300.00
  • EUR 704.00
  • EUR 356.00
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  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

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  • EUR 829.00
  • EUR 425.00
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  • EUR 258.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

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  • EUR 328.00
  • EUR 829.00
  • EUR 425.00
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  • 100 ug
  • 1 mg
  • 200 ug
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  • 500 tests
  • 50 tests

Interleukin 8 (IL8) Antibody

20-abx177199
  • EUR 356.00
  • EUR 133.00
  • EUR 1038.00
  • EUR 523.00
  • EUR 300.00
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Interleukin 8 (IL8) Antibody

20-abx177201
  • EUR 1191.00
  • EUR 578.00
  • 1 mg
  • 200 ug

Interleukin 8 (IL8) Antibody

20-abx173191
  • EUR 356.00
  • EUR 913.00
  • EUR 467.00
  • EUR 154.00
  • EUR 272.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Interleukin 8 (IL8) Antibody Pair

abx117314-1pair5x96wellplates 1 pair (5x96 well plates)
EUR 1010

Interleukin 8 / IL8 (CXCL8) Antibody

20-abx109944
  • EUR 411.00
  • EUR 1845.00
  • EUR 599.00
  • EUR 182.00
  • EUR 300.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Interleukin 8 / IL8 (CXCL8) Antibody

20-abx113257
  • EUR 732.00
  • EUR 398.00
  • 150 ul
  • 50 ul

Interleukin 8 / IL8 (CXCL8) Antibody

20-abx110542
  • EUR 411.00
  • EUR 1845.00
  • EUR 599.00
  • EUR 182.00
  • EUR 300.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Interleukin 8 / IL8 (CXCL8) Antibody

20-abx110581
  • EUR 411.00
  • EUR 1845.00
  • EUR 599.00
  • EUR 182.00
  • EUR 300.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Interleukin 8 / IL8 (CXCL8) Antibody

20-abx317929
  • EUR 411.00
  • EUR 1845.00
  • EUR 599.00
  • EUR 182.00
  • EUR 300.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Cow Interleukin 8 (IL8) Protein

20-abx651537
  • EUR 662.00
  • EUR 272.00
  • EUR 2040.00
  • EUR 787.00
  • EUR 481.00
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Interleukin 8 (IL8) Antibody Pair

20-abx370066
  • EUR 1177.00
  • EUR 773.00
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370068
  • EUR 1998.00
  • EUR 1261.00
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370095
  • EUR 1205.00
  • EUR 787.00
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370128
  • EUR 1706.00
  • EUR 1094.00
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370248
  • EUR 1177.00
  • EUR 773.00
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370249
  • EUR 1497.00
  • EUR 968.00
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370251
  • EUR 1539.00
  • EUR 996.00
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370256
  • EUR 1790.00
  • EUR 1135.00
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370625
  • EUR 1428.00
  • EUR 926.00
  • 10 × 96 tests
  • 5 × 96 tests

Interleukin 8 (IL8) Antibody Pair

20-abx370655
  • EUR 1915.00
  • EUR 1219.00
  • 10 × 96 tests
  • 5 × 96 tests

Cow Interleukin 8 (IL8) Protein

20-abx654060
  • EUR 648.00
  • EUR 272.00
  • EUR 1998.00
  • EUR 773.00
  • EUR 467.00
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Goat Interleukin 8 (IL8) Protein

20-abx654061
  • EUR 648.00
  • EUR 272.00
  • EUR 1998.00
  • EUR 773.00
  • EUR 467.00
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Horse Interleukin 8 (IL8) Protein

abx670162-20ug 20 ug
EUR 704

Human Interleukin 8 (IL8) Protein

abx670179-25ug 25 ug
EUR 551

Human Interleukin 8 (IL8) Protein

abx670180-25ug 25 ug
EUR 565

Pig Interleukin 8 (IL8) Protein

abx670316-5ug 5 ug
EUR 411

Rabbit Interleukin 8 (IL8) Protein

abx670328-5ug 5 ug
EUR 411

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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