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 in vivo. (A) The intensity of immunostaining for macrophages migrating towards the islet surfaces of rats transplanted with either untreated islets (CTL; n = 3) or islets treated with liraglutide (Lira; n = 3) and with (W) or without (Wo) liraglutide injections (n = 4). (B) The intensity of immunostaining for insulin in the CTL and liraglutide groups with (W) or without (Wo) liraglutide injections. (C) Immunostaining of macrophages and insulin 1 day post‐grafting for the CTL and liraglutide groups with or without liraglutide injections. Nuclear DAPI staining is shown in blue and insulin staining in green; macrophages are stained red; these three stains are merged. Results were expressed as mean ± SEM. *P < 0.05, significantly different as indicated; 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-0006: The anti‐inflammatory effect of liraglutide in vivo. (A) The intensity of immunostaining for macrophages migrating towards the islet surfaces of rats transplanted with either untreated islets (CTL; n = 3) or islets treated with liraglutide (Lira; n = 3) and with (W) or without (Wo) liraglutide injections (n = 4). (B) The intensity of immunostaining for insulin in the CTL and liraglutide groups with (W) or without (Wo) liraglutide injections. (C) Immunostaining of macrophages and insulin 1 day post‐grafting for the CTL and liraglutide groups with or without liraglutide injections. Nuclear DAPI staining is shown in blue and insulin staining in green; macrophages are stained red; these three stains are merged. Results were expressed as mean ± SEM. *P < 0.05, significantly different as indicated; one‐way ANOVA with Tukey's test.

Mentions: The anti‐inflammatory effect of liraglutide was evaluated in vivo 24 h post‐transplantation by measuring the amount of macrophage infiltration. Immunostaining experiments demonstrated significantly decreased macrophage infiltration at 24 h post‐transplantation in the group receiving islets pretreated with liraglutide and liraglutide injections post‐transplantation (Figure 6A). The comparison of untreated control and liraglutide‐injected control groups did reach significance (P = 0.08 ; Figs. 6A and 6C). Finally, a significant improvement of insulin intensity was observed only in liraglutide pretreatment groups at 24 h post‐grafting, compared with that of rats receiving control islets (Figure 6B). Comparison of the untreated control with the liraglutide pretreatment + liraglutide injections group did not achieve significance (P = 0.08 ; Figs 6B and C).


Improvement of islet graft function using liraglutide is correlated with its anti ‐ inflammatory properties
The anti‐inflammatory effect of liraglutide in vivo. (A) The intensity of immunostaining for macrophages migrating towards the islet surfaces of rats transplanted with either untreated islets (CTL; n = 3) or islets treated with liraglutide (Lira; n = 3) and with (W) or without (Wo) liraglutide injections (n = 4). (B) The intensity of immunostaining for insulin in the CTL and liraglutide groups with (W) or without (Wo) liraglutide injections. (C) Immunostaining of macrophages and insulin 1 day post‐grafting for the CTL and liraglutide groups with or without liraglutide injections. Nuclear DAPI staining is shown in blue and insulin staining in green; macrophages are stained red; these three stains are merged. Results were expressed as mean ± SEM. *P < 0.05, significantly different as indicated; 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-0006: The anti‐inflammatory effect of liraglutide in vivo. (A) The intensity of immunostaining for macrophages migrating towards the islet surfaces of rats transplanted with either untreated islets (CTL; n = 3) or islets treated with liraglutide (Lira; n = 3) and with (W) or without (Wo) liraglutide injections (n = 4). (B) The intensity of immunostaining for insulin in the CTL and liraglutide groups with (W) or without (Wo) liraglutide injections. (C) Immunostaining of macrophages and insulin 1 day post‐grafting for the CTL and liraglutide groups with or without liraglutide injections. Nuclear DAPI staining is shown in blue and insulin staining in green; macrophages are stained red; these three stains are merged. Results were expressed as mean ± SEM. *P < 0.05, significantly different as indicated; one‐way ANOVA with Tukey's test.
Mentions: The anti‐inflammatory effect of liraglutide was evaluated in vivo 24 h post‐transplantation by measuring the amount of macrophage infiltration. Immunostaining experiments demonstrated significantly decreased macrophage infiltration at 24 h post‐transplantation in the group receiving islets pretreated with liraglutide and liraglutide injections post‐transplantation (Figure 6A). The comparison of untreated control and liraglutide‐injected control groups did reach significance (P = 0.08 ; Figs. 6A and 6C). Finally, a significant improvement of insulin intensity was observed only in liraglutide pretreatment groups at 24 h post‐grafting, compared with that of rats receiving control islets (Figure 6B). Comparison of the untreated control with the liraglutide pretreatment + liraglutide injections group did not achieve significance (P = 0.08 ; Figs 6B and C).

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