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. 2021 Sep 21;11(1):18724.
doi: 10.1038/s41598-021-98158-7.

Vanillin modulates activities linked to dysmetabolism in psoas muscle of diabetic rats

Affiliations

Vanillin modulates activities linked to dysmetabolism in psoas muscle of diabetic rats

Veronica F Salau et al. Sci Rep. .

Abstract

Skeletal muscles are important in glucose metabolism and are affected in type 2 diabetes (T2D) and its complications. This study investigated the effect of vanillin on redox imbalance, cholinergic and purinergic dysfunction, and glucose-lipid dysmetabolism in muscles of rats with T2D. Male albino rats (Sprague-Dawley strain) were fed 10% fructose ad libitum for 2 weeks before intraperitoneally injecting them with 40 mg/kg streptozotocin to induce T2D. Low (150 mg/kg bodyweight (BW)) and high (300 mg/kg BW) doses of vanillin were orally administered to diabetic rats. Untreated diabetic rats and normal rats made up the diabetic control (DC) and normal control (NC) groups, respectively. The standard antidiabetic drug was metformin. The rats were humanely put to sleep after 5 weeks of treatment and their psoas muscles were harvested. There was suppression in the levels of glutathione, activities of SOD, catalase, ENTPDase, 5'Nucleotidase and glycogen levels on T2D induction. This was accompanied by concomitantly elevated levels of malondialdehyde, serum creatine kinase-MB, nitric oxide, acetylcholinesterase, ATPase, amylase, lipase, glucose-6-phosphatase (G6Pase), fructose-1,6-biphophastase (FBPase) and glycogen phosphorylase activities. T2D induction further resulted in the inactivation of fatty acid biosynthesis, glycerolipid metabolism, fatty acid elongation in mitochondria and fatty acid metabolism pathways. There were close to normal and significant reversals in these activities and levels, with concomitant reactivation of the deactivated pathways following treatment with vanillin, which compared favorably with the standard drug (metformin). Vanillin also significantly increased muscle glucose uptake ex vivo. The results suggest the therapeutic effect of vanillin against muscle dysmetabolism in T2D as portrayed by its ability to mitigate redox imbalance, inflammation, cholinergic and purinergic dysfunctions, while modulating glucose-lipid metabolic switch and maintaining muscle histology.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Chemical structure of vanillin.
Figure 2
Figure 2
Antioxidant status of experimental groups. Value = mean ± SD; n = 5. *Statistically significant (p < 0.05) to DC; #Statistically significant (p < 0.05) to NC. NC = normal rats, DC = diabetic control, DVL = diabetic rats + vanillin (150 mg/kg b.w), DVH = diabetic rats + vanillin (300 mg/kg bw), DMT = diabetic rats + metformin (200 mg/kg b.w), and NVX = normal rats + vanillin (300 mg/kg bw).
Figure 3
Figure 3
Nitric oxide levels of experimental groups. Value = mean ± SD; n = 5. *Statistically significant (p < 0.05) to DC; #Statistically significant (p < 0.05) to NC. NC = normal rats, DC = diabetic control, DVL = diabetic rats + vanillin (150 mg/kg b.w), DVH = diabetic rats + vanillin (300 mg/kg bw), DMT = diabetic rats + metformin (200 mg/kg b.w), and NVX = normal rats + vanillin (300 mg/kg bw).
Figure 4
Figure 4
Acetylcholinesterase activities of experimental groups. Value = mean ± SD; n = 5. *Statistically significant (p < 0.05) to DC; #Statistically significant (p < 0.05) to NC. NC = normal rats, DC = diabetic control, DVL = diabetic rats + vanillin (150 mg/kg b.w), DVH = diabetic rats + vanillin (300 mg/kg bw), DMT = diabetic rats + metformin (200 mg/kg b.w), and NVX = normal rats + vanillin (300 mg/kg bw).
Figure 5
Figure 5
(A) ATPase, (B) E-NTPDase and (C) 5′NTD activities of experimental groups. Value = mean ± SD; n = 5. *Statistically significant (p < 0.05) to DC; #Statistically significant (p < 0.05) to NC. NC = normal rats, DC = diabetic control, DVL = diabetic rats + vanillin (150 mg/kg b.w), DVH = diabetic rats + vanillin (300 mg/kg bw), DMT = diabetic rats + metformin (200 mg/kg b.w), and NVX = Normal rats + vanillin (300 mg/kg bw).
Figure 6
Figure 6
(A) Glucose 6-phosphatase, (B) FRUCTOSE-1,6-biphosphatase, (C) glycogen phosphorylase and (D) α-amylase activities of experimental groups. Value = mean ± SD; n = 5. *Statistically significant (p < 0.05) to DC; #Statistically significant (p < 0.05) to NC. NC = normal rats, DC = diabetic control, DVL = diabetic rats + vanillin (150 mg/kg b.w), DVH = diabetic rats + vanillin (300 mg/kg bw), DMT = diabetic rats + metformin (200 mg/kg b.w), and NVX = normal rats + vanillin (300 mg/kg bw).
Figure 7
Figure 7
Glycogen content of experimental groups. Value = mean ± SD; n = 5. *Statistically significant (p < 0.05) to DC; #Statistically significant (p < 0.05) to NC. NC = normal rats, DC = diabetic control, DVL = diabetic rats + vanillin (150 mg/kg b.w), DVH = diabetic rats + vanillin (300 mg/kg bw), DMT = diabetic rats + metformin (200 mg/kg b.w), and NVX = normal rats + vanillin (300 mg/kg bw).
Figure 8
Figure 8
Lipase activities of experimental groups. Value = mean ± SD; n = 5. *Statistically significant (p < 0.05) to DC; #Statistically significant (p < 0.05) to NC. NC = normal rats, DC = diabetic control, DVL = diabetic rats + vanillin (150 mg/kg b.w), DVH = diabetic rats + vanillin (300 mg/kg bw), DMT = diabetic rats + metformin (200 mg/kg b.w), and NVX = normal rats + vanillin (300 mg/kg bw).
Figure 9
Figure 9
(A) Heat map; and (B) Score plot between the selected PCs of GC–MS identified lipid metabolites.
Figure 10
Figure 10
Enrichment ratio of identified pathways in experimantal muscle tissues. NC = normal rats, DC = diabetic control, DVL = diabetic rats + vanillin (150 mg/kg b.w), DVH = diabetic rats + vanillin (300 mg/kg bw), DMT = diabetic rats + metformin (200 mg/kg b.w), and NVX = normal rats + vanillin (300 mg/kg bw).
Figure 11
Figure 11
Serum CK-MB concentrations of experimental groups. Value = mean ± SD; n = 5. *Statistically significant (p < 0.05) to DC; #Statistically significant (p < 0.05) to NC. NC = normal rats, DC = diabetic control, DVL = diabetic rats + vanillin (150 mg/kg b.w), DVH = diabetic rats + vanillin (300 mg/kg bw), DMT = diabetic rats + metformin (200 mg/kg b.w), and NVX = normal rats + vanillin (300 mg/kg bw).
Figure 12
Figure 12
Histological changes in the muscles of experimental groups. magnification =  × 400. f—muscle fascicles; d—degenerating muscle fibres; black arrows—myocyte nuclei; blue arrows—inflammatory infiltrate. NC = normal rats, DC = diabetic control, DVL = diabetic rats + vanillin (150 mg/kg b.w), DVH = diabetic rats + vanillin (300 mg/kg bw), DMT = diabetic rats + metformin (200 mg/kg b.w), and NVX = normal rats + vanillin (300 mg/kg bw).
Figure 13
Figure 13
Effect of vanillin on glucose uptake in isolated rat psoas muscle. Data = mean ± SD; n = 3. a-dValues with different letters above the bars for a given concentration are significantly (p < 0.05) different from each other.
Figure 14
Figure 14
(A) 3D and (B) 2D representations of docked complexes of the active site of GLUT4 with vanillin.

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