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This study aimed to evaluate hypoglycemic and hypolipidemic activities of Spirulina Platensis and its bioactive components (phycocyanin (PC), phycocyanopeptide (PCP) and phycocyanobilin (PCB)) on male diabetic Rats compared to controls and glibenclamide drug. For this reason, male Albino rats were equally divided into seven groups designated as normal control, diabetic control, diabetic + glibenclamide (Glyburide) drug (600 µg kg−1 body weight), diabetic + Spirulina biomass suspension (50 mg/ml/ kg−1 body weight), diabetic + phycocyanin (50 mg kg−1 body weight), diabetic + phycocyanopeptide (49 mg kg−1 body weight) and diabetic + phycocyanobilin (982 µg kg−1 body weight). The results show a statistically significant reduction (P < 0.05) level of fasting blood glucose, insulin resistance and lipids levels in diabetic animals administration with Spirulina Platensis, phycocyanin, phycocyanopeptide and phycocyanobilin compared with diabetic control. Also, there were an increase in HDL–cholesterol levels and β-cell function in these treatments. Histopathologically, diabetic rats treated with spirulina, PC, PCP induced a slight improve of pancreatic cells and an obvious recovery of pancreatic cells. The expression of insulin secretion from cells (β-cells) of diabetic rats was improved in the groups treated with Spirulina, phycocyanin, phycocyanopeptide. While, diabetic rats treated with phycocyanobilin recorded insulin levels lower than them. From this study it can be concluded that Spirulina Platensis, phycocyanin, phycocyanopeptide and phycocyanobilin possessed hypoglycemic, insulin sensitivity and hypolipidemic effects. Hypoglycemic and hypolipidemic effects of Spirulina Platensis may be attributed to phenolic compounds and phycocyanin. The antidiabetic effect of PC is most likely due to its ability to reduction of insulin resistance, enhance β-cell function and recovery of β-cells. The effect of PC may be attributed to selenium-binding phycocyanopeptide or/ and phycocyanobilin responsible for the antioxidant activity and chromium-binding phycocyanopeptide which activates insulin receptors.

Background and Purpose FM19G11 up-regulates mammalian target of rapamycin (mTOR)/hypoxia inducible factor-1α (HIF-1α) and PI3K/Akt pathways, which are involved in endothelial function. We evaluated the effects of FM19G11 on defective endothelial vasodilatation in arteries from rats and humans and investigated the mechanisms involved. Experimental Approach Effects of chronic in vivo administration of FM19G11 on aortic endothelial vasodilatation were evaluated together with ex vivo treatment in aortic and mesenteric arteries from control and insulin-resistant rats (IRR). Its effects on vasodilator responses of penile arteries (HPRAs) and corpus cavernosum (HCC) from men with vasculogenic erectile dysfunction (ED) (model of human endothelial dysfunction) were also evaluated. Vascular expression of phosphorylated-endothelial NOS (p-eNOS), phosphorylated-Akt (p-Akt) and HIF-1α was determined by immunodetection and cGMP by elisa. Key Results Chronic administration of FM19G11 reversed the impaired endothelial vasodilatation in IRR. Ex vivo treatment with FM19G11 also significantly improved endothelium-dependent vasodilatation in aorta and mesenteric arteries from IRR. These effects were accompanied by the restoration of p-eNOS and cGMP levels in IRR aorta and were prevented by either NOS or PI3K inhibition. p-Akt and p-eNOS contents were increased by FM19G11 in aortic endothelium of IRR. FM19G11-induced restoration of endothelial vasodilatation was unaffected by mTOR/HIF-1α inhibitors. FM19G11 also restored endothelial vasodilatation in HPRA and HCC from ED patients. Conclusions and Implications Stimulation of the PI3K/Akt/eNOS pathway by FM19G11 alleviates impaired NO-mediated endothelial vasodilatation in rat and human arteries independently of mTOR/HIF-1α activation. This pharmacological strategy could be beneficial for managing pathological conditions associated with endothelial dysfunction, such as ED.

Background aims Stem cells may be a promising therapy for acute respiratory distress syndrome. Recent in vivo and in vitro studies suggested that the mesenchymal stromal cells (MSCs) have anti-oxidative stress properties. We hypothesized that intravenous injection of bone marrow–derived mesenchymal stem cells (MSCs) could attenuate Escherichia coli –induced acute lung injury (ALI) in mice by controlling the oxidative stress status. Methods Eighty mice were randomly divided into four groups: group 1 (control group) received 25 μL of saline as a vehicle; group 2 contained E coli –induced ALI mice; group 3 included mice that received MSCs before induction of ALI; group 4 included mice that received MSCs after induction of ALI. Lung samples were isolated and assayed for oxidative stress variables and histopathologic analysis. Total anti-oxidant capacity was measured in broncho-alveolar lavage. Results Pre- and post-injury MSC injection increased survival, reduced pulmonary edema and attenuated lung injuries in ALI mice. Histologically, MSCs exhibited a considerable degree of preservation of the pulmonary alveolar architecture. An increase of anti-oxidant enzyme activities and a decrease of myeloperoxidase activity and malondialdehyde levels in the MSC recipient groups versus the ALI group were found. Furthermore, the total anti-oxidant capacity and reduced glutathione levels were significantly increased in MSCs recipient groups versus the ALI group. Weak +ve inducible nitric oxide synthase immuno-expression in groups that received MSCs was detected. Pre-injury MSC injection showed better effects than did post-injury MSC injection. Conclusions Systemic bone marrow–derived MSC injection was effective in modulating the oxidative stress status in E coli –induced acute lung injury in mice.

Amylin is co-secreted with insulin, responds to the same stimuli, is anorectic, lowers body weight by reducing fat mass, and is proposed for diabetes treatment. We examined the effect of a 3-day constant infusion of close to physiological doses of amylin in Wistar rats, on glucotransporter expression, glycogen content (G), glycogen synthase a activity (GSa) and glucose transport (GT), in liver, muscle and fat from insulin resistant (IR) and type 2 diabetic (T2D) models, compared to normal (N) animals; plasma glucose and insulin were measured. Plasma insulin in IR was higher than in N or T2D, and amylin normalized the value. In both, IR and T2D, liver G was lower than normal, accompanied by GLUT-2, mRNA and protein, higher and lower, respectively, than in N; amylin normalized G in both groups, without changes in GLUT-2, except for an mRNA increase in T2D. In IR and T2D, muscle GSa was reduced, together with respective over- and under-GLUT-4 expression; amylin induced only a trend toward GSa normalization in both groups. In isolated adipocytes, GT and GLUT-4 in IR and T2D were lower and higher, respectively, than in N; after amylin, not only GT was normalized in both groups but also the response to insulin was much more pronounced, including that in N, without major changes in GLUT-4. This suggests that the beneficial effect of amylin in states running with altered glucose homeostasis could occur by partially acting on the hexose metabolism of the liver and mainly on that of the adipose tissue.

Vascular disease has been involved in the pathophysiology of frailty. However, the role of endothelial dysfunction, an obligatory step preceding vascular disease, is unknown. We addressed this issue in two phases: – searching if aging per se is accompanied by endothelial dysfunction in microvessels from human beings of different ages (range 18-89) free of cardiovascular risk factors or cardiovascular disease; – searching if endothelial dysfunction (assessed by high ADMA levels) is associated to frailty in older people enrolled in a cohort study (Toledo Study of Healthy Aging). Results Endothelial dysfunction is present in older people due to an increased oxidative stress and the presence of inflammation in the vascular wall (Rodriguez Manas et al., Aging Cell 2009) and ADMA levels are higher in frail people, in people without cardiovascular disease and after adjustment by Ankle-Brachial Index as a biomarker of subclinical disease (Alonso-Bouzon et al., Age 2013). Conclusion Different experimental approaches (from the bench to the population-based studies) exhibit a nice complementariness to ask research questions in older people. These findings have raised new hypotheses that are now being tested in EU funded projects (FRAILOMIC, FRAILCLINIC) led by our group to test biomarkers useful for the diagnosis and prognosis of frailty.