ECE2016 Oral Communications Diabetes therapy & complications (5 abstracts)
TRAIL treatment reduces high-fat diet-induced hyperglycemia and hyperinsulinemia
Stella Bernardi 1 , Fleur Bossi 1 , Veronica Tisato 2 , Stefania Biffi 4 , Andrea Lorenzon 3 , Barbara Toffoli 1 , Giorgio Zauli 4, , Paola Secchiero 2 & Bruno Fabris 1
1University of Trieste, Trieste, Italy; 2University of Ferrara, Ferrara, Italy; 3Cluster in Biomedicine (CBM), Trieste, Italy; 4IRCCS Burlo Garofolo, Trieste, Italy.
Introduction: Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis-inducing ligand) may have an important role in the treatment of type 2 diabetes mellitus (T2DM). It has been shown that TRAIL deficiency worsens T2DM and that TRAIL delivery, when it is given before disease onset, slows down T2DM development. This study aimed at evaluating whether TRAIL had the potential not only to prevent, but also to treat T2DM.
Methods/design: 30 male C57bl6J mice aged 8 weeks were randomly assigned to a standard diet (CNT, n=10), or a high-fat diet (HFD, n=20), providing 60% of calories from fat. After 4 weeks, HFD-fed mice were further randomized to receive either placebo (HFD, n=10) or TRAIL (HFD + TRAIL, n=10), which was delivered weekly by intraperitoneal injection. Body weight, food intake, fasting glucose and insulin were measured at baseline and every 4 weeks. GTT (glucose tolerance test) and ITT (insulin tolerance test) were performed at 6 and 12 weeks. After 12 weeks of study, the distribution of Cy5.5-labelled TRAIL was evaluated by whole-body scan. Then, mice were sacrificed and bloods and tissues (pancreas, quadricep, liver, adipose tissue) collected for further analyses.
Results: Cy5.5-labelled TRAIL gave the highest signal a few hours after being injected. Not with standing its rapid clearance, at the end of the study, TRAIL reduced body weight gain, without affecting food intake. Moreover, TRAIL reduced the hyperglycemia and the hyperinsulinemia displayed by the HFD-fed mice both at fasting and during the 12-week GTT, and it also significantly lowered glucose levels during the 12-week ITT, indicating an improvement in the peripheral response to insulin.
Conclusion: This study confirms the ability of TRAIL to significantly attenuate the metabolic abnormalities induced by a HFD, and shows that TRAIL is effective also when it is given after disease onset.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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