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. 2018 Aug;14(5):1163-1172.
doi: 10.5114/aoms.2016.63285. Epub 2016 Oct 26.

Hypoglycaemic activity of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione in streptozotocin-induced diabetic mice through ameliorating metabolic function and regulating peroxisome proliferator-activated receptor γ

Kintoko Kintoko  1 , Xiaohui Xu  1 , Xing Lin  1 , Yang Jiao  1 , Qingwei Wen  1 , Zhaoni Chen  1 , Jinbin Wei  1 , Tao Liang  1 , Renbin Huang  1
Affiliations
Free PMC article

Hypoglycaemic activity of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione in streptozotocin-induced diabetic mice through ameliorating metabolic function and regulating peroxisome proliferator-activated receptor γ

Kintoko Kintoko et al. Arch Med Sci. 2018 Aug.
Free PMC article

Abstract

Introduction: Diabetes mellitus is characterized by hyperglycaemia causing changes in plasma lipoproteins, which leads to insulin resistance, secretion defects or both. The present study aimed to evaluate the ability of 2-dodecyl-6-methoxy-cyclohexa-2,5-diene-1,4-dione (DMDD) isolated from Averrhoa carambola L. roots to lower hyperglycaemia and to investigate its potential mechanism in diabetic mice.

Material and methods: DMDD was isolated using a column chromatographic technique. Experimental mice were fed with a high-fat diet for a month and were intravenously injected with streptozotocin (80 mg/kg, single dose). Diabetic mice were orally administered DMDD (12.5, 25, 50 mg/kg) and 50 mg/kg pioglitazone for 15 days. Fasting blood glucose (FBG), fasting blood insulin (FINS), pancreatic insulin content, interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), as well as serum total cholesterol (TC), triglyceride (TG) and free fatty acid (FFA) were determined. Adipose tissue was assessed by histological examination, immunohistochemistry, western blot and reverse transcription-polymerase chain reaction methods.

Results: DMDD significantly increased the insulin level (all p < 0.05). In contrast, FBG, IL-6, TNF-α, TC, TG and FFA were significantly decreased (all p < 0.05). However, DMDD induced the activation of adipocyte peroxisome proliferator-activated receptor γ (PPAR-γ), confirmed by increased protein and mRNA expression of PPAR-γ.

Conclusions: DMDD possessed hypoglycaemic activity due to its potential mechanism involving PPARγ-mediated adipocyte endocrine regulation.

Keywords: Averrhoa carambola L.; adipocyte; diabetes; endocrine; mechanism; peroxisome proliferator-activated receptor γ.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione
Figure 2
Figure 2
Effect of DMDD on lipid profiles. All values are given as mean ± SEM (10 mice in each group) *p < 0.05 compared with normal group; Δp < 0.05 compared with diabetes group.
Figure 3
Figure 3
Effect of DMDD on serum contents of IL-6 and TNF-α. All values are given as mean ± SEM (10 mice in each group) *p < 0.05 compared with normal group; Δp < 0.05 compared with diabetic group.
Figure 4
Figure 4
Histological observations of pancreas tissue. A – Normal mice, B – untreated diabetic mice, C – diabetic mice treated with 50 mg/kg pioglitazone, D – 12.5 mg/kg of DMDD, E – 25 mg/kg of DMDD, F – 50 mg/kg of DMDD
Figure 5
Figure 5
Effect of DMDD on insulin level in pancreas tissue. All values are given as mean ± SEM (10 mice in each group) *p < 0.05 compared with normal group; Δp < 0.05 compared with diabetic group.
Figure 6
Figure 6
Histological observations of epididymal fat. A – Normal mice, B – untreated diabetic mice, C – diabetic mice treated with 50 mg/kg pioglitazone, D – 12.5 mg/kg of DMDD, E – 25 mg/kg of DMDD, F – 50 mg/kg of DMDD All values are given as mean ± SEM (10 mice in each group), *p < 0.05 compared with normal group, Δp < 0.05 compared with diabetic group.
Figure 7
Figure 7
Effect of DMDD on immunohistochemistry of epididymal fat. A – Normal mice, B – untreated diabetic mice, C – diabetic mice treated with 50 mg/kg pioglitazone, D – 12.5 mg/kg of DMDD, E – 25 mg/kg of DMDD, F – 50 mg/kg of DMDD All values are given as mean ± SEM (10 mice in each group), *p < 0.05 compared with normal group, Δp < 0.05 compared with diabetic group.
Figure 8
Figure 8
Effect of DMDD on expression of PPAR-γ protein All values are given as mean ± SEM (10 mice in each group), *p < 0.05 compared with normal group, Δp < 0.05 compared with diabetic group.
Figure 9
Figure 9
Effect of DMDD on expression of PPAR-γ mRNA All values are given as mean ± SEM (10 mice in each group), *p < 0.05 compared with normal group, Δp < 0.05 compared with diabetic group.
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