ECE2018 Oral Communications Novel insights into prediabetes and type 2 diabetes (5 abstracts)
Effects of TRAIL delivery on an experimental model of type 2 diabetes and diabetic nephropathy
Stella Bernardi 1 , Barbara Toffoli 2 , Veronica Tisato 3 , Andrea Lorenzon 4 , Giorgio Zauli 3 , Paola Secchiero 3 & Bruno Fabris 1
1Università degli Studi di Trieste, Trieste, Italy; 2IRCCS Burlo Garofolo, Trieste, Italy; 3Università degli Studi di Ferrara, Trieste, Italy; 4CBM scrl, Trieste, Italy.
Introduction: Experimental studies suggest that a circulating protein called TRAIL (TNF-related apoptosis-inducing ligand) has the potential to treat type 2 diabetes mellitus (T2DM). We have recently demonstrated that TRAIL delivery ameliorates T2DM in the high-fat diet-fed mouse. This study aimed at evaluating whether TRAIL had the potential to treat not only T2DM but also diabetic nephropathy.
Methods/design: Based on this background, 15 male db/H mice aged 8 weeks were randomly assigned to saline (CNT, n=10) or TRAIL treatment (CNT+T, n=5), together with 20 male db/db mice which were randomly assigned to saline (db/db, n=10) or TRAIL treatment (db/db+T, n=10). TRAIL was delivered at the dose of 20 microg/mouse twice per week. Body weight, food intake, fasting glucose and insulin, as well as albuminuria were measured at baseline and every 4 weeks. GTT (glucose tolerance test) and ITT (insulin tolerance test) were performed at the end of the study. Then, mice were sacrificed and bloods and tissues were collected for further analyses.
Results: In the db/db mouse, TRAIL treatment did not affect body weight and glucose metabolism, which might be due to the extreme phenotype exhibited by this genetic model of obesity. Nevertheless, TRAIL delivery significantly reduced glomerular hypertrophy and glomerulosclerosis, indicating a potential therapeutic effect on diabetic nephropathy. This might involve prosurvival/proapoptotic pathways and anti-inflammatory effects.
Conclusion: This study sheds light on TRAIL therapeutic potential against diabetic nephropathy.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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