Differential effects of acute (extenuating) and chronic (training) exercise on inflammation and oxidative stress status in an animal model of type 2 diabetes mellitus.

This study compares the effects of a single bout of exercise (acute extenuating) with those promoted by an exercise training program (chronic), focusing on low-grade chronic inflammation profile and on oxidative stress status, using the obese ZDF rats as a model of type 2 diabetes mellitus (T2DM). Animals were sacrificed after 12 weeks of a swimming training program and after a single bout of acute extenuating exercise. Glycaemic, insulinemic, and lipidic profile (triglycerides, total-cholesterol) were evaluated, as well as inflammatory (serum CRPhs, TNF-α, adiponectin) and oxidative (lipidic peroxidation and uric acid) status. When compared to obese diabetic sedentary rats, the animals submitted to acute exercise presented significantly lower values of glycaemia and insulinaemia, with inflammatory profile and oxidative stress significantly aggravated. The trained animals showed amelioration of glycaemic and lipidic dysmetabolism, accompanied by remarkable reduction of inflammatory and oxidative markers. In conclusion, the results presented herein suggessted that exercise pathogenesis-oriented interventions should not exacerbate underlying inflammatory stress associated with T2DM.

Effects of sitagliptin treatment on dysmetabolism, inflammation, and oxidative stress in an animal model of type 2 diabetes (ZDF rat).

The purpose of this paper is to evaluate the chronic effect of sitagliptin on metabolic profile, inflammation, and redox status in the Zucker Diabetic Fatty (ZDF) rat, an animal model of obese type 2 diabetes. Diabetic and obese ZDF (fa/fa) rats and their controls (ZDF +/+) were treated during 6 weeks with vehicle (control) and sitagliptin (10 mg/kg/bw). Glucose, HbA1c, insulin, Total-c, TGs, IL-1beta, TNF-alpha, CRPhs, and adiponectin were assessed in serum and MDA and TAS in serum, pancreas, and heart. Pancreatic histology was also evaluated. Sitagliptin in diabetic rats promoted a decrease in glucose, HbA1c, Total-c, and TGs accompanied by a partial prevention of insulinopenia, together, with a decrease in CRPhs and IL-1beta. Sitagliptin also showed a positive impact on lipid peroxidation and hypertension prevention. In conclusion, chronic sitagliptin treatment corrected the glycaemic dysmetabolism, hypertriglyceridaemia, inflammation, and hypertension, reduced the severity of the histopathological lesions of pancreatic endocrine and exocrine tissues, together with a favourable redox status, which might be a further advantage in the management of diabetes and its proatherogenic comorbidities.

Occupationally Acquired Q Fever in Shepherds and Sheep Milk Cheesemakers.

Q fever is a zoonosis caused by Coxiella burnetii, and transmission to humans is often associated with contact with ovine and caprine livestock. Those exposed to sheep are particularly at high risk of infection. Recent studies show that Q fever is increasing in sheep farms in Portugal raising alerts on spillover to humans. We detected anti-C. burnetii IgG in shepherds and sheep milk cheesemakers (27 [28.1%] in a total of 96; 95% confidence interval [CI] 19.4-38.2%) and in controls (21 [8.1%] in a total of 260; 95% CI 5.1-12.1%), pointing to an increased risk of C. burnetii infection (P = 0.0001), with an odds ratio for anti-C. burnetii of 4.45 (95% CI 2.4-8.4%; P = 0.0001), in individuals with occupational contact with sheep in Portugal.

Renoprotective Effects of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin: A Review in Type 2 Diabetes.

Diabetic nephropathy (DN) is now the single commonest cause of end-stage renal disease (ESRD) worldwide and one of the main causes of death in diabetic patients. It is also acknowledged as an independent risk factor for cardiovascular disease (CVD). Since sitagliptin was approved, many studies have been carried out revealing its ability to not only improve metabolic control but also ameliorate dysfunction in various diabetes-targeted organs, especially the kidney, due to putative underlying cytoprotective properties, namely, its antiapoptotic, antioxidant, anti-inflammatory, and antifibrotic properties. Despite overall recommendations, many patients spend a long time well outside the recommended glycaemic range and, therefore, have an increased risk for developing micro- and macrovascular complications. Currently, it is becoming clearer that type 2 diabetes mellitus (T2DM) management must envision not only the improvement in glycaemic control but also, and particularly, the prevention of pancreatic deterioration and the evolution of complications, such as DN. This review aims to provide an overview of the current knowledge in the field of renoprotective actions of sitagliptin, namely, improvement in diabetic dysmetabolism, hemodynamic factors, renal function, diabetic kidney lesions, and cytoprotective properties.

The Place of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Therapeutics: A "Me Too" or "the Special One" Antidiabetic Class?

Incretin-based therapies, the most recent therapeutic options for type 2 diabetes mellitus (T2DM) management, can modify various elements of the disease, including hypersecretion of glucagon, abnormal gastric emptying, postprandial hyperglycaemia, and, possibly, pancreatic ß cell dysfunction. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) increase glucagon-like peptide-1 (GLP-1) availability and correct the "incretin defect" seen in T2DM patients. Clinical studies have shown good glycaemic control with minimal risk of hypoglycaemia or any other adverse effects, despite the reports of pancreatitis, whose association remains to be proved. Recent studies have been focusing on the putative ability of DPP-4 inhibitors to preserve pancreas function, in particular due to the inhibition of apoptotic pathways and stimulation of ß cell proliferation. In addition, other cytoprotective effects on other organs/tissues that are involved in serious T2DM complications, including the heart, kidney, and retina, have been increasingly reported. This review outlines the therapeutic potential of DPP-4 inhibitors for the treatment of T2DM, focusing on their main features, clinical applications, and risks, and discusses the major challenges for the future, in particular the possibility of becoming the preferred therapy for T2DM due to their ability to modify the natural history of the disease and ameliorate nephropathy, retinopathy, and cardiovascular complications.