Decrease of PPAR δ in Type-1-Like Diabetic Rat for Higher Mortality after Spinal Cord Injury

Hsu

et al. 2017

Clin Exp Pharma Physio

Morin is a flavonoid contained in guava that is known to reduce hyperglycemia in diabetes. Insulin secretion has been demonstrated to increase following the administration of morin. The present study is designed to investigate the potential mechanism(s) of morin-induced insulin secretion in the MIN6 cell line. First, we identified that morin induced a dose-dependent increase in insulin secretion and intracellular calcium content in MIN6 cells. Morin potentiated glucose-stimulated insulin secretion (GSIS). Additionally, we used siRNA for the ablation of imidazoline receptor protein (NISCH) expression in MIN6 cells. Interestingly, the effects of increased insulin secretion by morin and canavanine were markedly reduced in Si-NISCH cells. Moreover, we used KU14R to block imidazoline I receptor (I-3R) that is known to enhance insulin release from the pancreatic β-cells. Without influence on the basal insulin secretion, KU14R dose-dependently inhibited the increased insulin secretion induced by morin or efaroxan in MIN6 cells. Additionally, effects of increased insulin secretion by morin or efaroxan were reduced by diazoxide at the dose sufficient to open K channels and attenuated by nifedipine at the dose used to inhibit L-type calcium channels. Otherwise, phospholipase C (PLC) is introduced to couple with imidazoline receptor (I-R). The PLC inhibitor dose-dependently inhibited the effects of morin in MIN6 cells. Similar blockade was also observed in protein kinase C (PKC) inhibitor-treated cells. Taken together, we found that morin increases insulin secretion via the activation of I-R in pancreatic cells. Therefore, morin would be useful to develop in the research and treatment of diabetic disorders.

Section: Discussionsupporting

confidence: 53%

Section: Methodsmentioning

confidence: 99%

Section: Western Blotting Analysismentioning

confidence: 99%

See 1 more Smart Citation

Investigation of morin‐induced insulin secretion in cultured pancreatic cells

Hsu

et al. 2017

Clin Exp Pharma Physio

“… 13 Additionally, the activation of PPARδ is helpful to improve the injury from SCI in diabetic rats. 14 The present study is thus designed to investigate the therapeutic potential of telmisartan in SCI using animal model as pre-clinical evidence.…”

Section: Introductionmentioning

confidence: 99%

Development of telmisartan in the therapy of spinal cord injury: pre-clinical study in rats

Tsai

Chang

et al. 2015

DDDT

Self Cite

BackgroundDecrease of peroxisome proliferator-activated receptors-δ (PPARδ) expression has been observed after spinal cord injury (SCI). Increase of PPARδ may improve the damage in SCI. Telmisartan, the antihypertensive agent, has been mentioned to increase the expression of PPARδ. Thus, we are going to screen the effectiveness of telmisartan in SCI for the development of it in clinical application.MethodsIn the present study, we used compressive SCI in rats. Telmisartan was then used to evaluate the influence in rats after SCI. Change in PPARδ expression was identified by Western blots. Also, behavioral tests were performed to check the recovery of damage.ResultsRecovery of damage from SCI was observed in telmisartan-treated rats. Additionally, this action of telmisartan was inhibited by GSK0660 at the dose sufficient to block PPARδ. However, metformin at the dose enough to activate adenosine monophosphate-activated protein kinase failed to produce similar action as telmisartan. Thus, mediation of adenosine monophosphate-activated protein kinase in this action of telmisartan can be rule out. Moreover, telmisartan reversed the expressions of PPARδ in rats with SCI.ConclusionThe obtained data suggest that telmisartan can improve the damage of SCI in rats through an increase in PPARδ expression. Thus, telmisartan is useful to be developed as an agent in the therapy of SCI.

Molecular Medicine Reports

“…It has been reported that PPAR participates in the pathogenesis of diseases, such as diabetes and SCI (24,25). In addition, it has been observed that the decrease of PPAR-δ expression in the spinal cord of streptozotocin (STZ)-diabetic rats may explain the higher mortality rate observed following SCI in STZ-diabetic rats (26). Thus, activation of PPAR-δ may reduce the severity of SCI, and PPAR-δ may be a target for therapy in SCI patients (27).…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes and pathways associated with spinal cord injury

Zhang

Song

Wang

et al. 2017

The present study was designed to identify key genes or significant signaling pathways associated with spinal cord injury (SCI), and to clarify the underlying molecular mechanisms of SCI. Data from the GSE45550 array were downloaded from the Gene Expression Omnibus database. A total of 6 control samples, 6 samples at 3 days post-SCI (SCI3d), 6 samples at 8 days post-SCI (SCI8d) and 6 samples at 14 days post-SCI (SCI14d) were included. The microarray data was preprocessed by the robust multi-array average algorithm. The differentially expressed genes (DEGs) were identified using the limma package. The overlapping DEGs among groups were analyzed using the Venny 2.0 online tool. Modules enriched by DEGs were selected by weighted gene co-expression network analysis. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes pathways were identified for DEGs using the Database for Annotation, Visualization and Integrated Discovery. A total of 693 genes were obtained by combining the DEGs of the SCI3d, SCI8d and SCI14d groups. The pink module and green module with smaller P-values obtained from weighted gene co-expression network analysis module analyses of DEGs demonstrated a higher correlation with SCI. In addition, the peroxisome proliferator-activated receptor (PPAR) signaling pathway that the cluster of differentiation 36 (CD36) was significantly enriched in, was one of the significant pathways in the pink module. The p53 signaling pathway that Caspase-3 (Casp3) was significantly enriched in was one of the significant pathways in the green module. In conclusion, the results of the present study demonstrated that the PPAR and p53 signaling pathway may serve important roles in the progression of SCI. In addition, CD36 and Casp3 may be involved in the progression of SCI via the PPAR and p53 signaling pathways, respectively.