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Study · Ex vivo tissue · 2021

12 results

GLP-2 Is Locally Produced From Human Islets and Balances Inflammation Through an Inter-Islet-Immune Cell Crosstalk.

He W, Rebello OD, Henne A, Nikolka F, Klein T, Maedler K

Frontiers in endocrinology5 Jul 2021Cited by 18 (Europe PMC)

PMID34290670 (opens in a new tab)PMCIDPMC8287580 (opens in a new tab)DOI10.3389/fendo.2021.697120 (opens in a new tab)PepBankPUB-34290670
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Summary

Glucagon-like peptide-1 (GLP-1) shows robust protective effects on β-cell survival and function and GLP-1 based therapies are successfully applied for type-2 diabetes (T2D) and obesity. Another cleavage product of pro-glucagon, Glucagon-like peptide-2 (GLP-2; both GLP-1 and GLP-2 are inactivated by DPP-4) has received little attention in its action inside pancreatic islets. In this study, we investigated GLP-2 production, GLP-2 receptor (GLP-2R) expression and the effect of GLP-2R activation in human islets. Isolated human islets from non-diabetic donors were exposed to diabetogenic conditions: high glucose, palmitate, cytokine mix (IL-1β/IFN-γ) or Lipopolysaccharide (LPS) in the presence or absence of the DPP4-inhibitor linagliptin, the TLR4 inhibitor TAK-242, the GLP-2R agonist teduglutide and/or its antagonist GLP-2(3-33). Human islets under control conditions secreted active GLP-2 (full-length, non-cleaved by DPP4) into the culture media, which was increased by combined high glucose/palmitate, the cytokine mix and LPS and highly potentiated by linagliptin. Low but reproducible GLP-2R mRNA expression was found in all analyzed human islet isolations from 10 donors, which was reduced by pro-inflammatory stimuli: the cytokine mix and LPS. GLP-2R activation by teduglutide neither affected acute or glucose stimulated insulin secretion nor insulin content. Also, teduglutide had no effect on high glucose/palmitate- or LPS-induced dysfunction in cultured human islets but dampened LPS-induced macrophage-dependent IL1B and IL10 expression, while its antagonist GLP-2(3-33) abolished such reduction. In contrast, the expression of islet macrophage-independent cytokines IL6, IL8 and TNF was not affected by teduglutide. Medium conditioned by teduglutide-exposed human islets attenuated M1-like polarization of human monocyte-derived macrophages, evidenced by a lower mRNA expression of pro-inflammatory cytokines, compared to vehicle treated islets, and a reduced production of itaconate and succinate, marker metabolites of pro-inflammatory macrophages. Our results reveal intra-islet production of GLP-2 and GLP-2R expression in human islets. Despite no impact on β-cell function, local GLP-2R activation reduced islet inflammation which might be mediated by a crosstalk between endocrine cells and macrophages.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study12

12 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabEx vivo tissueEfficacy outcome

    In isolated human islets, teduglutide did not affect acute insulin secretion.

    In plain wordsIn lab tests, teduglutide did not change acute insulin release from human islets.

    Peptide
    Teduglutide
    Outcome
    No significant changeAcute insulin secretion
    Study

    humann: not reported in source

    Isolated human islets
    Outcome group
    Glycemic control · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    GLP-2R activation by teduglutide neither affected acute or glucose stimulated insulin secretion nor insulin content.
    1 context sentence
    Summary · context
    Isolated human islets from non-diabetic donors were exposed to diabetogenic conditions: high glucose, palmitate, cytokine mix (IL-1β/IFN-γ) or Lipopolysaccharide (LPS) in the presence or absence of the DPP4-inhibitor linagliptin, the TLR4 inhibitor TAK-242, the GLP-2R agonist teduglutide and/or its antagonist GLP-2(3-33).
  2. 02LabEx vivo tissueEfficacy outcome

    In isolated human islets, teduglutide did not affect glucose-stimulated insulin secretion.

    In plain wordsIn lab tests, teduglutide did not change glucose-stimulated insulin release from human islets.

    Peptide
    Teduglutide
    Outcome
    No significant changeGlucose-stimulated insulin secretion
    Study

    humann: not reported in source

    Isolated human islets
    Outcome group
    Glycemic control · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    GLP-2R activation by teduglutide neither affected acute or glucose stimulated insulin secretion nor insulin content.
    1 context sentence
    Summary · context
    Isolated human islets from non-diabetic donors were exposed to diabetogenic conditions: high glucose, palmitate, cytokine mix (IL-1β/IFN-γ) or Lipopolysaccharide (LPS) in the presence or absence of the DPP4-inhibitor linagliptin, the TLR4 inhibitor TAK-242, the GLP-2R agonist teduglutide and/or its antagonist GLP-2(3-33).
  3. 03LabEx vivo tissueEfficacy outcome

    In isolated human islets, teduglutide did not affect insulin content.

    In plain wordsIn lab tests, teduglutide did not change insulin content in human islets.

    Peptide
    Teduglutide
    Outcome
    No significant changeInsulin content
    Study

    humann: not reported in source

    Isolated human islets
    Outcome group
    Glycemic control · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    GLP-2R activation by teduglutide neither affected acute or glucose stimulated insulin secretion nor insulin content.
    1 context sentence
    Summary · context
    Isolated human islets from non-diabetic donors were exposed to diabetogenic conditions: high glucose, palmitate, cytokine mix (IL-1β/IFN-γ) or Lipopolysaccharide (LPS) in the presence or absence of the DPP4-inhibitor linagliptin, the TLR4 inhibitor TAK-242, the GLP-2R agonist teduglutide and/or its antagonist GLP-2(3-33).
  4. 04LabEx vivo tissueEfficacy outcome

    In cultured human islets, teduglutide did not affect high glucose/palmitate-induced dysfunction.

    In plain wordsIn lab tests, teduglutide did not change human islet dysfunction induced by high glucose and palmitate.

    Peptide
    Teduglutide
    Outcome
    No significant changeHigh glucose/palmitate-induced dysfunction
    Study

    humann: not reported in source

    Isolated human islets
    Outcome group
    Glycemic control · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Also, teduglutide had no effect on high glucose/palmitate- or LPS-induced dysfunction in cultured human islets
    1 context sentence
    Summary · context
    Isolated human islets from non-diabetic donors were exposed to diabetogenic conditions: high glucose, palmitate, cytokine mix (IL-1β/IFN-γ) or Lipopolysaccharide (LPS) in the presence or absence of the DPP4-inhibitor linagliptin, the TLR4 inhibitor TAK-242, the GLP-2R agonist teduglutide and/or its antagonist GLP-2(3-33).
  5. 05LabEx vivo tissueEfficacy outcome

    In cultured human islets, teduglutide did not affect LPS-induced dysfunction.

    In plain wordsIn lab tests, teduglutide did not change LPS-induced dysfunction in human islets.

    Peptide
    Teduglutide
    Outcome
    No significant changeLPS-induced dysfunction
    Study

    humann: not reported in source

    Isolated human islets
    Outcome group
    Glycemic control · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Also, teduglutide had no effect on high glucose/palmitate- or LPS-induced dysfunction in cultured human islets
    1 context sentence
    Summary · context
    Isolated human islets from non-diabetic donors were exposed to diabetogenic conditions: high glucose, palmitate, cytokine mix (IL-1β/IFN-γ) or Lipopolysaccharide (LPS) in the presence or absence of the DPP4-inhibitor linagliptin, the TLR4 inhibitor TAK-242, the GLP-2R agonist teduglutide and/or its antagonist GLP-2(3-33).
  6. 06LabEx vivo tissueEfficacy outcome

    In human islets, teduglutide dampened LPS-induced macrophage-dependent IL1B expression.

    In plain wordsIn lab tests, teduglutide reduced LPS-induced macrophage-dependent IL1B expression in human islets.

    Peptide
    Teduglutide
    Outcome
    DecreaseIL1B expression
    Study

    humann: not reported in source

    Isolated human islets
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    but dampened LPS-induced macrophage-dependent IL1B and IL10 expression
    1 context sentence
    Summary · context
    Isolated human islets from non-diabetic donors were exposed to diabetogenic conditions: high glucose, palmitate, cytokine mix (IL-1β/IFN-γ) or Lipopolysaccharide (LPS) in the presence or absence of the DPP4-inhibitor linagliptin, the TLR4 inhibitor TAK-242, the GLP-2R agonist teduglutide and/or its antagonist GLP-2(3-33).
  7. 07LabEx vivo tissueEfficacy outcome

    In human islets, teduglutide dampened LPS-induced macrophage-dependent IL10 expression.

    In plain wordsIn lab tests, teduglutide reduced LPS-induced macrophage-dependent IL10 expression in human islets.

    Peptide
    Teduglutide
    Outcome
    DecreaseIL10 expression
    Study

    humann: not reported in source

    Isolated human islets
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    but dampened LPS-induced macrophage-dependent IL1B and IL10 expression
    1 context sentence
    Summary · context
    Isolated human islets from non-diabetic donors were exposed to diabetogenic conditions: high glucose, palmitate, cytokine mix (IL-1β/IFN-γ) or Lipopolysaccharide (LPS) in the presence or absence of the DPP4-inhibitor linagliptin, the TLR4 inhibitor TAK-242, the GLP-2R agonist teduglutide and/or its antagonist GLP-2(3-33).
  8. 08LabEx vivo tissueEfficacy outcome

    In human islets, teduglutide did not affect macrophage-independent IL6, IL8 and TNF expression.

    In plain wordsIn lab tests, teduglutide did not change macrophage-independent IL6, IL8 and TNF expression in human islets.

    Peptide
    Teduglutide
    Outcome
    No significant changeMacrophage-independent cytokine expression
    Study

    humann: not reported in source

    Isolated human islets
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In contrast, the expression of islet macrophage-independent cytokines IL6, IL8 and TNF was not affected by teduglutide.
    1 context sentence
    Summary · context
    Isolated human islets from non-diabetic donors were exposed to diabetogenic conditions: high glucose, palmitate, cytokine mix (IL-1β/IFN-γ) or Lipopolysaccharide (LPS) in the presence or absence of the DPP4-inhibitor linagliptin, the TLR4 inhibitor TAK-242, the GLP-2R agonist teduglutide and/or its antagonist GLP-2(3-33).
  9. 09LabIn vitro (cells)Mechanism

    In human macrophages, medium from teduglutide-exposed islets attenuated M1-like polarization compared with medium from vehicle-treated islets.

    In plain wordsIn lab tests, medium from teduglutide-exposed human islets reduced inflammatory macrophage polarization compared with medium from vehicle-treated islets.

    Peptide
    Teduglutide
    Outcome
    DecreaseM1-like macrophage polarization
    Study

    humann: not reported in source

    Human monocyte-derived macrophages exposed to medium conditioned by teduglutide-exposed human islets
    Comparator
    Medium conditioned by vehicle-treated human islets
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Medium conditioned by teduglutide-exposed human islets attenuated M1-like polarization of human monocyte-derived macrophages, evidenced by a lower mRNA expression of pro-inflammatory cytokines, compared to vehicle treated islets
  10. 10LabIn vitro (cells)Mechanism

    In human macrophages, medium from teduglutide-exposed islets lowered pro-inflammatory cytokine mRNA expression compared with medium from vehicle-treated islets.

    In plain wordsIn lab tests, medium from teduglutide-exposed human islets lowered inflammatory cytokine gene expression compared with medium from vehicle-treated islets.

    Peptide
    Teduglutide
    Outcome
    DecreasePro-inflammatory cytokine mRNA expression
    Study

    humann: not reported in source

    Human monocyte-derived macrophages exposed to medium conditioned by teduglutide-exposed human islets
    Comparator
    Medium conditioned by vehicle-treated human islets
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Medium conditioned by teduglutide-exposed human islets attenuated M1-like polarization of human monocyte-derived macrophages, evidenced by a lower mRNA expression of pro-inflammatory cytokines, compared to vehicle treated islets
  11. 11LabIn vitro (cells)Mechanism

    In human macrophages, medium from teduglutide-exposed islets reduced itaconate production compared with medium from vehicle-treated islets.

    In plain wordsIn lab tests, medium from teduglutide-exposed human islets reduced macrophage itaconate production compared with medium from vehicle-treated islets.

    Peptide
    Teduglutide
    Outcome
    DecreaseItaconate production
    Study

    humann: not reported in source

    Human monocyte-derived macrophages exposed to medium conditioned by teduglutide-exposed human islets
    Comparator
    Medium conditioned by vehicle-treated human islets
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Medium conditioned by teduglutide-exposed human islets attenuated M1-like polarization of human monocyte-derived macrophages, evidenced by a lower mRNA expression of pro-inflammatory cytokines, compared to vehicle treated islets
    1 context sentence
    Summary · context
    and a reduced production of itaconate and succinate, marker metabolites of pro-inflammatory macrophages.
  12. 12LabIn vitro (cells)Mechanism

    In human macrophages, medium from teduglutide-exposed islets reduced succinate production compared with medium from vehicle-treated islets.

    In plain wordsIn lab tests, medium from teduglutide-exposed human islets reduced macrophage succinate production compared with medium from vehicle-treated islets.

    Peptide
    Teduglutide
    Outcome
    DecreaseSuccinate production
    Study

    humann: not reported in source

    Human monocyte-derived macrophages exposed to medium conditioned by teduglutide-exposed human islets
    Comparator
    Medium conditioned by vehicle-treated human islets
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Medium conditioned by teduglutide-exposed human islets attenuated M1-like polarization of human monocyte-derived macrophages, evidenced by a lower mRNA expression of pro-inflammatory cytokines, compared to vehicle treated islets
    1 context sentence
    Summary · context
    and a reduced production of itaconate and succinate, marker metabolites of pro-inflammatory macrophages.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:37 UTC

    First added · source update from Europe PMC

Subjects

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