Treatment with Recombinant Tumor Necrosis Factor-related Apoptosis-inducing Ligand Alleviates the Severity of Streptozotocin-induced Diabetes

Overview

Journal Diabetes

Specialty Endocrinology

Date 2010 Feb 27

PMID 20185810

Citations 22

Authors

Giorgio Zauli

Barbara Toffoli

Maria Grazia di Iasio

Claudio Celeghini

Bruno Fabris

Paola Secchiero

Affiliations

Soon will be listed here.

Abstract

Objective: To evaluate the potential therapeutic effect of recombinant human tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) treatment in a model of type 1 diabetes.

Research Design And Methods: Recombinant TRAIL was added in vitro to primary human and mouse peripheral blood mononuclear cells (PBMCs) and isolated human islets to evaluate the expression of the immunoregulatory gene SOCS1. Diabetes was induced by five consecutive daily injections of low-concentration (50 mg/kg) streptozotocin (STZ) in C57 black mice (n = 24). A group of these mice (n = 12) was co-injected with recombinant TRAIL (20 microg/day) for 5 days, and the diabetic status (glycemia and body weight) was followed over time. After 6 weeks, circulating levels of insulin, TNF-alpha, and osteoprotegerin (OPG) were measured, and animals were killed to perform the histological analysis of the pancreas.

Results: The in vitro exposure of both PBMCs and human islets to recombinant TRAIL significantly upregulated the expression of SOCS1. With respect to STZ-treated animals, mice co-injected with STZ+TRAIL were characterized by 1) lower levels of hyperglycemia, 2) higher levels of body weight and insulinemia, 3) a partial preservation of pancreatic islets with normal morphology, and 4) a lower expression of both systemic (TNF-alpha and OPG) and pancreatic (vascular cell adhesion molecule [VCAM]-1) inflammatory markers.

Conclusions: Overall, these data demonstrate that the administration of recombinant TRAIL ameliorates the severity of STZ-induced type 1 diabetes, and this effect was accompanied by the upregulation of SOCS1 expression.

Citing Articles

Immunomodulatory Functions of TNF-Related Apoptosis-Inducing Ligand in Type 1 Diabetes.

Fogarasi M, Dima S Cells. 2024; 13(20.

PMID: 39451194 PMC: 11506310. DOI: 10.3390/cells13201676.

Palmitic Acid Induced a Long-Lasting Lipotoxic Insult in Human Retinal Pigment Epithelial Cells, which Is Partially Counteracted by TRAIL.

Sergi D, Zauli E, Casciano F, Secchiero P, Zauli G, Fields M Antioxidants (Basel). 2022; 11(12).

PMID: 36552548 PMC: 9774631. DOI: 10.3390/antiox11122340.

Repositioning the Role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) on the TRAIL to the Development of Diabetes Mellitus: An Update of Experimental and Clinical Evidence.

Koliaki C, Katsilambros N Int J Mol Sci. 2022; 23(6).

PMID: 35328646 PMC: 8949963. DOI: 10.3390/ijms23063225.

TRAIL/DR5 pathway promotes AKT phosphorylation, skeletal muscle differentiation, and glucose uptake.

Toffoli B, Tonon F, Tisato V, Zauli G, Secchiero P, Fabris B Cell Death Dis. 2021; 12(12):1089.

PMID: 34789726 PMC: 8599458. DOI: 10.1038/s41419-021-04383-3.

FTZ Ameliorates Diabetic Cardiomyopathy by Inhibiting Inflammation and Cardiac Fibrosis in the Streptozotocin-Induced Model.

Wang L, Wu H, Deng Y, Zhang S, Wei Q, Yang Q Evid Based Complement Alternat Med. 2021; 2021:5582567.

PMID: 34621323 PMC: 8492284. DOI: 10.1155/2021/5582567.

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