effectiveness of beta adrenoceptor antagonists on progression of insulin resistance and type 2 diabetes in high fat diet-fed rats

The effects of carvedilol a third generation beta-blocker on progression of insulin resistance and type 2 diabetes mellitus were compared to the prototypic non-selective beta-blocker, propranolol. Male albino rats were fed a high fat diet [HFD] for 3 months to induce insulin resistance and mild type 2 diabetes [T2DM] Oral administration of carvedilol [2 or 20 mg/kg], propranolol [30 mg/kg], or vehicle was started along with HFD in different groups. Indices of body composition and insulin resistance, oral glucose tolerance, fasting serum insulin levels, lipid profile, serum levels of lipid peroxidation markers as well as levels of advanced glycosylation end products were determined. In high fat-fed animals, an increase in body composition index, area under the oral glucose tolerance curve, fasting serum insulin, and insulin resistance were observed in comparison to normal diet controls. In addition, significant dyslipidemic changes were also observed in these animals. Moreover, in concordance with these hyperglycemic and dyslipidemic changes, HFD significantly increased serum levels of markers of lipid peroxidation and advanced glycosylation end products [AGEs]. On the other hand, beta-adrenergic blockers treatment showed better effects on glucose disposal, insulin levels, and insulin resistance. However, carvedilol treatments showed enhanced lipid profiles and lower AGEs when compared to propranolol treatment in HFD animals. These preferential metabolic effects of carvedilol can be attributed to its antioxidant effects and negative regulation of lipolysis. We concluded that carvedilol have protective effects against the development of insulin resistance and T2DM, in addition to amelioration of the consequent cardiovascular complications

Evaluation of the effects of rofecoxib and nitric oxide-releasing aspirin on stress-induced gastric ulcers in rats

The study was conducted to investigate possible mechanisms of the protective actions of rofecoxib [a selective COX-2 inhibitor] and nitric oxide-releasing aspirin [NO-aspirin] against experimentally induced gastric lesions in rats. The rats were randomly assigned to vehicle [carboxymethylcellulose], rofecoxib [5 mg/Kg] and NO-aspirin [55mg/Kg]-pretreated groups, in addition to the non-stressed control group. Gastric lesions were induced by exposing the rats to 3 hrs cold restraint stress [CRS] and ulcer indices were determined. Gastric juice parameters [pH, free and total acid output, mucin and pepsin concentrations] were determined. The stomachs were used for determination of gastric mucosal level of lipid peroxides as well as total nitrites. Results showed that both rofecoxib and NO-aspirin displayed protective effects against lesions formation. Pretreatment with both drugs significantly lowered gastric acid secretion, mucin and pepsin concentrations as well as mucosal levels of lipid peroxides and total nitrites compared to CRS rats. This protection was possibly mediated through lowering of gastric juice acid secretion and proteolytic activity and increasing mucin concentration as well as free radical scavenging and reduction of the detrimental increase of nitric oxide during CRS

Antidiabetic effect of portulaca oleracea extract, alone and plus gliclazide, on streptozotocin-nicotinamide-induced type 2 diabetes in rats

Type 2 diabetes is rapidly emerging as a pandemic. To identify an alternative or adjunctive approach to existing medications, the antidiabetic effect of Portulaca oleracea extract [PE], alone and plus gliclazide [Gl], was investigated on streptozotocin [STZ]-nicotinamide-induced type 2 diabetes in rats. Oral administration of the PE, alone and plus Gl, to diabetic rats for 15 and 30 days resulted in a significant decrease in the level of blood glucose, with a concomitant increase in serum insulin level as compared to untreated diabetic rats. The antidiabetic activity was observed to be time-dependent and was most effective in a combined treatment of PE with a reduced dose of Gl. In addition, enzymatic antioxidant superoxide dismutase [SOD] and nonenzymatic antioxidants: reduced glutathione [GSH] and vitamin-C were significantly increased after the same periods of treatment except vitamin-C which significantly increased only after 30 days. In conclusion, in type 2 diabetic rats PE shows an antidiabetic action which may be mediated, at least in part, by compensating for defective insulin release and enhancing antioxidant status. The combined therapy of PE plus Gl has better antidiabetic activity than PE individual therapy. Therefore, Portulaca oleracea can be recommended as an adjunctive support for therapy of type 2 diabetes