Hypertension in CB57BL/6J mouse model of non-insulin-dependent diabetes mellitus

Mills, E; Kuhn, Cynthia M.; Feinglos, Mark N.

doi:10.1152/ajpregu.1993.264.1.r73

Cited by 52 publications

(60 citation statements)

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“…Our findings can possibly be interpreted as relevant for humans, as our study-used daidzein and equol concentrations that are within the range encountered in various populations that consume foods rich in isoflavones, and C57BL/6J mice have phenotype similar to that of human disease; the induction of obesity and insulin resistance under ad libitum access to a high-fat diet, and the maintenance of normal conditions under restriction to a low-fat chow diet, as in humans. [61][62][63] In addition, it will be the epoch-making discovery that daidzein affects ChREBP signaling, adiponectin and ghrelin as their relationships have yet to be assessed.…”

Section: Discussionmentioning

confidence: 99%

Daidzein supplementation prevents non-alcoholic fatty liver disease through alternation of hepatic gene expression profiles and adipocyte metabolism

et al. 2010

Int J Obes

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Introduction: Globally, non-alcoholic fatty liver disease (NAFLD) continues to rise and isoflavones exert antisteatotic effects by the regulation of hepatic lipogenesis/insulin resistance or adiposity/a variety of adipocytokines are related to hepatic steatosis. However, there is very little information regarding the potential effects of daidzein, the secondary abundant isoflavone, on NAFLD. Here, we have assessed the hepatic global transcription profiles, adipocytokines and adiposity in mice with high fat-induced NAFLD and their alteration by daidzein supplementation. Methods: C57BL/6J mice were fed with normal fat (16% fat of total energy), high fat (HF; 36% fat of total energy) and HF supplemented with daidzein (0.1, 0.5, 1 and 2 g per kg diet) for 12 weeks. Results: Daidzein supplementation (X0.5 g per kg diet) reduced hepatic lipid concentrations and alleviated hepatic steatosis. The hepatic microarray showed that daidzein supplementation (1 g per kg diet) downregulated carbohydrate responsive element binding protein, a determinant of de novo lipogenesis, its upstream gene liver X receptor b and its target genes encoding for lipogenic enzymes, thereby preventing hepatic steatosis and insulin resistance. These results were confirmed by lower insulin and blood glucose levels as well as homeostasis model assessment insulin resistance scores. In addition, daidzein supplementation inhibited adiposity by the upregulation of genes involved in fatty acid b-oxidation and the antiadipogeneis, and moreover augmented antisteatohepatitic leptin and adiponectin mRNA levels, whereas it reduced the mRNA or concentration of steatotic tumor necrosis factor a and ghrelin. Conclusions: These findings show that daidzein might alleviate NAFLD through the direct regulation of hepatic de novo lipogenesis and insulin signaling, and the indirect control of adiposity and adipocytokines by the alteration of adipocyte metabolism.

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Section: Discussionmentioning

confidence: 99%

Daidzein supplementation prevents non-alcoholic fatty liver disease through alternation of hepatic gene expression profiles and adipocyte metabolism

et al. 2010

Int J Obes

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“…To the best of our knowledge, the possible involvement of renal GSK3 in hypertension has not been examined. HF diet has been suggested to cause mild hypertension in C57/6J mice [18,20,21]. To determine if GSK3 plays a significant role in BP regulation in hyperinsulinaemic and insulin-resistant mice, we treated mice with GSK3 inhibitor peptide.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study we explored the effect of GSK3 inhibition on glucose metabolism in an environmentally induced (high-fat [HF] diet) insulin-resistant obese mouse model of type 2 diabetes. Several studies have indicated that the C57BL/6J mouse strain on an HF diet is a suitable model for noninsulin-dependent diabetes mellitus and hypertension [18][19][20][21]. We chose this model because it closely mimics the common form of obesity and insulin resistance associated with human type 2 diabetes.…”

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confidence: 99%

Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice

et al. 2006

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Aims/hypothesis In the current study, the effect of a highly specific peptide inhibitor of glycogen synthase kinase 3 (GSK3) (L803-mts) on glucose metabolism and BP was examined in a high-fat (HF) fed mouse model of diabetes. Methods C57/BL6J mice were placed on an HF diet for 3 months and treated with L803-mts for 20 days, following which glucose metabolism was examined by euglycaemichyperinsulinaemic clamp studies. BP and heart rate were measured by radio-telemetry. Results The HF mice were obese, with impaired glucose tolerance and high plasma insulin and leptin levels. L803-mts treatment significantly reduced the insulin levels and doubled the glucose infusion rate required to maintain a euglycaemic condition in the HF+L803-mts group compared with the HF group. Insulin failed to suppress the endogenous glucose production rate in the HF group while decreasing it by 75% in the HF+L803-mts group, accompanied by increased liver glycogen synthase activity and net hepatic glycogen synthesis. GSK3 inhibition also reduced peripheral insulin resistance. Plasma glucose disappearance rate increased by 60% in the HF+L803-mts group compared with the HF group. In addition, glucose uptake in heart and gastrocnemius muscle was markedly improved. Although mean arterial pressure increased following the HF diet, it did not change significantly during the 12 days of L803-mts treatment. Conclusions/interpretation These studies demonstrate that GSK3 inhibition improved hepatic and peripheral insulin resistance in a mouse model of HF-induced diabetes, but it failed to have an effect on BP. GSK3 may represent an important therapeutic target for insulin resistance.

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“…Body weight, food and water ingestion were measured weekly throughout the study. This experimental model has been previously shown to induce obesity, type 2 diabetes mellitus and hypertension in C57BL/6 mice (Mills et al, 1993).…”

Section: Methodsmentioning

confidence: 97%

Attenuation of the cardiovascular and metabolic complications of obesity in CD14 knockout mice

et al. 2008

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Aims: Although toll-like receptors (TLR) are known to mediate the metabolic complications of obesity, the mechanisms underlying its activation remain largely unknown. The present study analyzed a model of dietinduced obesity in mice lacking the TLR4/TLR2 co-receptor CD14. Main methods: Six-week-old male mice lacking CD14 (n = 16) were allocated to either a control diet or a highfat high-simple carbohydrate diet (5.4 kcal/g; 35% fat; 35% sucrose), and compared with C57BL/6 (WT; n = 15) controls. After 12 weeks, body composition, basal sympathetic activity, non-invasive blood pressure and glucose tolerance were evaluated. Hepatic and adipose tissues were collected for mRNA quantification, histology and LPS incubation. Key findings: In both WT and CD14 knockout mice, obesity was accompanied by TLR2 and TLR4 upregulation. However, obese mice lacking CD14 presented decreased lipid and macrophage content in hepatic and adipose tissues, lower urinary levels of noradrenaline, decreased systolic blood pressure, reduced fasting plasma glucose and blunted glucose intolerance, compared with obese WT group. In the presence of exogenous sCD14, adipose tissue incubation with LPS-induced TLR2 and TNF-α upregulation in both WT and CD14 knockout obese mice. Significance: In our model of diet-induced obesity, mice lacking CD14 showed lower adiposity and hepatic steatosis, improved glucose homeostasis, blunted sympathetic overactivity and reduced blood pressure elevation. This was observed in the presence of preserved TLR4 and TLR2 gene expression, and intact TLR4 signaling pathways. These results suggest that CD14-mediated TLR activation might contribute to the cardiovascular and metabolic complications of obesity.

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Hypertension in CB57BL/6J mouse model of non-insulin-dependent diabetes mellitus

Cited by 52 publications

References 0 publications

Daidzein supplementation prevents non-alcoholic fatty liver disease through alternation of hepatic gene expression profiles and adipocyte metabolism

Daidzein supplementation prevents non-alcoholic fatty liver disease through alternation of hepatic gene expression profiles and adipocyte metabolism

Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice

Attenuation of the cardiovascular and metabolic complications of obesity in CD14 knockout mice

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