Limits...
Improvement of islet graft function using liraglutide is correlated with its anti ‐ inflammatory properties

View Article: PubMed Central - PubMed

ABSTRACT

Background and purpose: Liraglutide improves the metabolic control of diabetic animals after islet transplantation. However, the mechanisms underlying this effect remain unknown. The objective of this study was to evaluate the anti‐inflammatory and anti‐oxidative properties of liraglutide on rat pancreatic islets in vitro and in vivo.

Experimental approach: In vitro, rat islets were incubated with 10 μmol·L−1 liraglutide for 12 and 24 h. Islet viability functionality was assessed. The anti‐inflammatory properties of liraglutide were evaluated by measuring CCL2, IL‐6 and IL‐10 secretion and macrophage chemotaxis. The anti‐oxidative effect of liraglutide was evaluated by measuring intracellular ROS and the total anti‐oxidative capacity. In vivo, 1000 islets were cultured for 24 h with or without liraglutide and then transplanted into the liver of streptozotocin‐induced diabetic Lewis rats with or without injections of liraglutide. Effects of liraglutide on metabolic control were evaluated for 1 month.

Key results: Islet viability and function were preserved and enhanced with liraglutide treatment. Liraglutide decreased CCL2 and IL‐6 secretion and macrophage activation after 12 h of culture, while IL‐10 secretion was unchanged. However, intracellular levels of ROS were increased with liraglutide treatment at 12 h. This result was correlated with an increase of anti‐oxidative capacity. In vivo, liraglutide decreased macrophage infiltration and reduced fasting blood glucose in transplanted rats.

Conclusions and implications: The beneficial effects of liraglutide on pancreatic islets appear to be linked to its anti‐inflammatory and anti‐oxidative properties. These findings indicated that analogues of glucagon‐like peptide‐1 could be used to improve graft survival.

No MeSH data available.


Related in: MedlinePlus

The anti‐inflammatory effect of liraglutide. (A) CCL2 secretion measured in the culture media of islets either left untreated (CTL) or treated with liraglutide (Lira) after 12 (n = 4 )and 24 h (n = 5) of culture. (B) A macrophage migration index was measured following the induction of migration in cultured macrophages by 10–6 mol·L−1 of N‐fMLP (positive control; n = 6), islet supernatant without prior treatment (CTL) or pretreatment with liraglutide. Tested supernatants were obtained after 12 (n = 4) and 24 h (n = 5) of culture. Results were expressed as mean ± SEM; n  = 4 (12h) or n  = 5 (24h). *P < 0.05, significantly different from corresponding CTL value; one‐way ANOVA with Tukey's test.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5120160&req=5

bph13575-fig-0002: The anti‐inflammatory effect of liraglutide. (A) CCL2 secretion measured in the culture media of islets either left untreated (CTL) or treated with liraglutide (Lira) after 12 (n = 4 )and 24 h (n = 5) of culture. (B) A macrophage migration index was measured following the induction of migration in cultured macrophages by 10–6 mol·L−1 of N‐fMLP (positive control; n = 6), islet supernatant without prior treatment (CTL) or pretreatment with liraglutide. Tested supernatants were obtained after 12 (n = 4) and 24 h (n = 5) of culture. Results were expressed as mean ± SEM; n  = 4 (12h) or n  = 5 (24h). *P < 0.05, significantly different from corresponding CTL value; one‐way ANOVA with Tukey's test.

Mentions: Secretion of CCL2 by cultured islets was increased, which corresponded with the results of chemotaxis tests. The addition of liraglutide significantly reduced CCL2 secretion by islets after 12 h of culture, compared with that of untreated islets (n = 4; Figure 2A). This finding was consistent with the significant decrease of macrophage migration induced by rat islet culture medium supernatant after 12 h in culture (n = 4; Figure 2B). However, after 24 h of culture, CCL2 secretion and chemotaxis in the liraglutide‐treated islets were comparable to those of untreated islets (n = 5; Figure 2A and B).


Improvement of islet graft function using liraglutide is correlated with its anti ‐ inflammatory properties
The anti‐inflammatory effect of liraglutide. (A) CCL2 secretion measured in the culture media of islets either left untreated (CTL) or treated with liraglutide (Lira) after 12 (n = 4 )and 24 h (n = 5) of culture. (B) A macrophage migration index was measured following the induction of migration in cultured macrophages by 10–6 mol·L−1 of N‐fMLP (positive control; n = 6), islet supernatant without prior treatment (CTL) or pretreatment with liraglutide. Tested supernatants were obtained after 12 (n = 4) and 24 h (n = 5) of culture. Results were expressed as mean ± SEM; n  = 4 (12h) or n  = 5 (24h). *P < 0.05, significantly different from corresponding CTL value; one‐way ANOVA with Tukey's test.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120160&req=5

bph13575-fig-0002: The anti‐inflammatory effect of liraglutide. (A) CCL2 secretion measured in the culture media of islets either left untreated (CTL) or treated with liraglutide (Lira) after 12 (n = 4 )and 24 h (n = 5) of culture. (B) A macrophage migration index was measured following the induction of migration in cultured macrophages by 10–6 mol·L−1 of N‐fMLP (positive control; n = 6), islet supernatant without prior treatment (CTL) or pretreatment with liraglutide. Tested supernatants were obtained after 12 (n = 4) and 24 h (n = 5) of culture. Results were expressed as mean ± SEM; n  = 4 (12h) or n  = 5 (24h). *P < 0.05, significantly different from corresponding CTL value; one‐way ANOVA with Tukey's test.
Mentions: Secretion of CCL2 by cultured islets was increased, which corresponded with the results of chemotaxis tests. The addition of liraglutide significantly reduced CCL2 secretion by islets after 12 h of culture, compared with that of untreated islets (n = 4; Figure 2A). This finding was consistent with the significant decrease of macrophage migration induced by rat islet culture medium supernatant after 12 h in culture (n = 4; Figure 2B). However, after 24 h of culture, CCL2 secretion and chemotaxis in the liraglutide‐treated islets were comparable to those of untreated islets (n = 5; Figure 2A and B).

View Article: PubMed Central - PubMed

ABSTRACT

Background and purpose: Liraglutide improves the metabolic control of diabetic animals after islet transplantation. However, the mechanisms underlying this effect remain unknown. The objective of this study was to evaluate the anti&#8208;inflammatory and anti&#8208;oxidative properties of liraglutide on rat pancreatic islets in vitro and in vivo.

Experimental approach: In vitro, rat islets were incubated with 10&nbsp;&mu;mol&middot;L&minus;1 liraglutide for 12 and 24&nbsp;h. Islet viability functionality was assessed. The anti&#8208;inflammatory properties of liraglutide were evaluated by measuring CCL2, IL&#8208;6 and IL&#8208;10 secretion and macrophage chemotaxis. The anti&#8208;oxidative effect of liraglutide was evaluated by measuring intracellular ROS and the total anti&#8208;oxidative capacity. In vivo, 1000 islets were cultured for 24&nbsp;h with or without liraglutide and then transplanted into the liver of streptozotocin&#8208;induced diabetic Lewis rats with or without injections of liraglutide. Effects of liraglutide on metabolic control were evaluated for 1&nbsp;month.

Key results: Islet viability and function were preserved and enhanced with liraglutide treatment. Liraglutide decreased CCL2 and IL&#8208;6 secretion and macrophage activation after 12&nbsp;h of culture, while IL&#8208;10 secretion was unchanged. However, intracellular levels of ROS were increased with liraglutide treatment at 12&nbsp;h. This result was correlated with an increase of anti&#8208;oxidative capacity. In vivo, liraglutide decreased macrophage infiltration and reduced fasting blood glucose in transplanted rats.

Conclusions and implications: The beneficial effects of liraglutide on pancreatic islets appear to be linked to its anti&#8208;inflammatory and anti&#8208;oxidative properties. These findings indicated that analogues of glucagon&#8208;like peptide&#8208;1 could be used to improve graft survival.

No MeSH data available.


Related in: MedlinePlus