Male C57BL/6J mice were used to determine the possible therapeutic effects of our previously described tart cherry extract in a chronic obesity mouse model on metabolic parameters, glucose tolerance, inflammatory mediators, and antioxidant capacity. The control group received standard mouse chow, and the high fat control group was switched to a high fat diet and tap water supplemented with 5% sucrose. The high fat + anthocyanin group received the high fat and sucrose diet, but received the anthocyanin-rich tart cherry extract dissolved in their drinking water. After six weeks, an oral glucose tolerance test was performed, and the water-soluble antioxidant capacity (ACW), superoxide dismutase (SOD) activity, and the plasma levels of insulin, C-peptide, leptin, IL-6, MCP-1, adiponectin and resistin were measured. The high fat diet increased body weight, reduced glucose tolerance, and caused an elevation in leptin, IL-6, MCP-1, and resistin levels. Furthermore, antioxidant capacity was decreased with a significant elevation of SOD activity. Anthocyanin treatment failed to reverse the effects of the high fat diet on body weight and glucose tolerance, but significantly reduced the leptin and IL-6 levels. The tart cherry extract also made a significant enhancement in antioxidant capacity and SOD activity. Our results show that chronic anthocyanin intake has a potential to enhance redox status and alleviate inflammation associated with obesity.
Background Clinical studies suggest a link between obesity and the primary headache disorder migraine. In our study we aimed to reveal the effect of obesity on meningeal nociceptor function in rats receiving a high-fat, high-sucrose diet. Methods Transient receptor potential ankyrin 1 (TRPA1) receptor activation-induced changes in meningeal blood flow, release of calcitonin gene-related peptide (CGRP) from trigeminal afferents and TRPA1 protein expression in the trigeminal ganglia were measured in control and obese rats. Metabolic parameters of the animals were assessed by measuring glucose and insulin homeostasis as well as plasma cytokine concentrations. Results The present experiments revealed an enhanced basal and TRPA1 receptor agonist-induced CGRP release from meningeal afferents of obese insulin-resistant rats and an attenuated CGRP release to potassium chloride. Obesity was also associated with an augmented vasodilatation in meningeal arteries after dural application of the TRPA1 agonist acrolein, a reduction in TRPA1 protein expression in the trigeminal ganglia and elevations in circulating proinflammatory cytokines IL-1β and IL-6 in addition to increased fasting blood glucose and insulin concentrations. Conclusions Our results suggest trigeminal sensitisation as a mechanism for enhanced headache susceptibility in obese individuals after chemical exposure of trigeminal nociceptors.
Background: Insulin resistance has been recognized as the most significant predictor of further development of type 2 diabetes mellitus (T2DM). Here we investigated the effect of a heat shock protein (HSP) co-inducer, BGP-15, on insulin sensitivity in different insulin-resistant animal models and compared its effect with insulin secretagogues and insulin sensitizers. Methods: Insulin sensitivity was assessed by the hyperinsulinemic euglycemic glucose clamp technique in normal and cholesterol-fed rabbits and in healthy Wistar and Goto-Kakizaki (GK) rats in dose-ranging studies. We also examined the effect of BGP-15 on streptozotocin-induced changes in the vasorelaxation of the aorta in Sprague-Dawley rats. Results: BGP-15 doses of 10 and 30 mg/kg increased insulin sensitivity by 50% and 70%, respectively, in cholesterolfed but not in normal rabbits. After 5 days of treatment with BGP-15, the glucose infusion rate was increased in a dose-dependent manner in genetically insulin-resistant GK rats. The most effective dose was 20 mg/kg, which showed a 71% increase in insulin sensitivity compared to control group. Administration of BGP-15 protected against streptozotocin-induced changes in vasorelaxation, which was similar to the effect of rosiglitazone. Conclusion: Our results indicate that the insulin-sensitizing effect of BGP-15 is comparable to conventional insulin sensitizers. This might be of clinical utility in the treatment of T2DM.
Our results suggest that obesity induced by long-term HFHS diet results in sensitization of the trigeminovascular system. Changes in TRPV1-mediated vascular reactions and CGRP release are pathophysiological alterations that may be of relevance to the enhanced headache susceptibility of obese individuals.
The major role of liver glycogen is to supply glucose to the circulation maintaining the normal blood glucose level. In muscle and liver the accumulation and breakdown of glycogen are regulated by the reciprocal activities of glycogen phosphorylase and glycogen synthase. Glycogen phosphorylase catalyses the key step of glycogen degradation and its activity can be inhibited by glucose and its analogues. Obviously, any readily accessible inhibitor of glycogen phosphorylase can be used as a potential therapy of non-insulin-dependent or type 2 diabetes. Hepatic glycogen phosphorylase has been identified as a new target for drugs that control blood glucose concentration. In our experiments glucopyranosylidene-spirothiohydantoin (TH) was tested on the insulin sensitivity and blood glucose level of control and streptozotocin-treated rats. The streptozotocin-treated rats failed to gain weight and exhibited stable hyperglycemia (4.7 ± 0.5 mmol/L glucose in control vs. 7.8 ± 0.5 mmol/L) and low plasma insulin levels (9.6 ± 1.9 µIU/mL in control vs. 3.2 ± 2.2 µIU/mL). When insulin supplementation with slow-release implants (2 IU/day) was started 8 weeks after streptozotocin injection, blood glucose concentration remained suppressed, plasma insulin level dramatically increased and the insulin sensitivity restored. TH administration significantly reduced the high blood glucose concentration and restored the insulin sensitivity of STZtreated rats.
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