The Role of Beta Cell Recovery in Type 2 Diabetes Remission.

Type 2 diabetes (T2D) has been considered a relentlessly worsening disease, due to the progressive deterioration of the pancreatic beta cell functional mass. Recent evidence indicates, however, that remission of T2D may occur in variable proportions of patients after specific treatments that are associated with recovery of beta cell function. Here we review the available information on the recovery of beta cells in (a) non-diabetic individuals previously exposed to metabolic stress; (b) T2D patients following low-calorie diets, pharmacological therapies or bariatric surgery; (c) human islets isolated from non-diabetic organ donors that recover from "lipo-glucotoxic" conditions; and (d) human islets isolated from T2D organ donors and exposed to specific treatments. The improvement of insulin secretion reported by these studies and the associated molecular traits unveil the possibility to promote T2D remission by directly targeting pancreatic beta cells.

An in vitro study of the peroxyl and hydroxyl radical scavenging capacity of the calcium antagonist amlodipine.

Amlodipine has been reported to improve endothelial function in patients with arterial hypertension and to significantly limit the progression of carotid atherosclerosis. The aim of this study was to assess the total antioxidant activity of amlodipine. We measured the in vitro antioxidant activity of amlodipine as its ability to antagonize the oxidation of alpha-keto-gamma-methiolbutyric acid by both hydroxyl and peroxyl radicals. The results are expressed as Total Oxyradical Scavenging Capacity (TOSC) units. Reduced glutathione, uric acid and trolox were used as the reference antioxidants. Amlodipine showed an efficiency as scavenger of peroxyl radicals (TOSC: 5945 +/- 544 units/mg) significantly higher (>50%, P <0.001) than that of GSH (2733 +/- 636 units/mg), and 70% lower (P < 0.0001) than the value obtained with uric acid (18144 +/- 696 units/mg) and trolox (17522 +/- 734 units/mg). Of interest, the scavenging capacity of amlodipine towards hydroxyl radicals (1455 +/- 154 units/mg) was 320% higher (P < 0.00001) than that of GSH (358 +/- 112 units/mg), 20% higher than that of uric acid (1198 +/- 121 units/mg), and 100% higher than that of trolox (759 +/- 143 units/mg). Amlodipine has intrinsic antioxidant activity with both anti-hydroxyl and anti-peroxyl radicals activity.

Left ventricular diastolic function and carotid artery wall in elderly athletes and sedentary controls.

Advancing age is characterized by structural and functional change of left ventricle (LV) and large elastic arteries. Recent advances in tissue Doppler imaging (TDI) and integrated backscatter (IBS), new ultrasound tools, have allowed non-invasive assessment of structural and functional characterization of myocardium and artery wall. Our aim was to compare LV diastolic function and carotid artery remodeling in elderly athletes and sedentary controls. Twenty-five elderly athletes (males, aged 68.6 +/- 4.2 years) were compared to 25 age-sex-matched sedentary controls. All the subjects underwent either conventional Doppler echocardiography with pulsed TDI to evaluate LV diastolic function, and conventional ultrasonography and integrated backscatter (IBS) analysis to evaluate the carotid wall. Corrected IBS values (C-IBS) were obtained by subtracting the IBS value of the adventitia. Body mass index and blood pressure were not different in the two groups; athletes showed lower heart rate (P < 0.0001) and, as expected, higher LV mass than sedentary subjects (P < 0.0001). Transmitral Doppler analysis showed in trained subjects a significantly lower peak A and a higher E/A ratio (P < 0.001). On regards to TDI measurements, athletes exhibited a higher Em, a lower Am, and, subsequently, an increased Em/Am ratio of both lateral wall and septum (P < 0.0001). The IVRTm was shorter in trained subjects (P < 0.001). Athletes showed a lower C-IBS (-26.8 +/- 2.9 vs. -23.4 +/- 3.8 dB, P < 0.001) and a smaller intima-media thickness (IMT: 0.66 +/- 0.14 vs. 0.80 +/- 0.18 mm, P < 0.001) respect to sedentary controls. Moreover, a significant direct correlation was found between Em/Am of LV septal and lateral wall and C-IBS values (respectively, r = 0.62 and r = 0.56, P < 0.001). Thus the aging heart manifests structural and functional changes in response to physical activity. The expected pattern of cardiac and arterial alterations normally seen in response to age is modified in the older athletes, suggesting the exercise training is an effective stimulus in shaping arterial structure and left ventricular function in older heart. It would appear that pulsed TDI and IBS analysis may play an important role in detecting training-induced LV and carotid artery structural and functional modifications.

Plasma antioxidant activity and cutaneous microvascular endothelial function in athletes and sedentary controls.

Aging is associated with endothelial dysfunction in both conduit arteries and peripheral microcirculation. Furthermore, aging is associated with an increased susceptibility to free radical mediated tissue damage. The aim of this study was to assess the relationship between age, regular aerobic-endurance training, plasma antioxidant activity and microcirculatory skin blood flow in healthy individuals. Thirty-six male athletes (range: 22-74 years; VO2max 54.3 +/- 5.2 ml/kg/min) and 36 age-sex-matched sedentary controls (range: 20-75 years; VO2max 34.2 +/- 3.4 ml/kg/min) were studied. Each group was divided into a younger (<30 years) and an older (>60 years) subgroup. Hand and foot baseline and stimulated skin blood flow (SBF) was measured by laser-Doppler flowmetry. Plasma free radicals antioxidant capacity against both peroxyl and hydroxyl radicals was also evaluated as Total Oxyradical Scavenging Capacity (TOSC) units. Baseline SBFs were not significantly different between athletes and sedentary groups, while plasma TOSC values against peroxyl radicals (18.4 +/- 3.1 vs. 13.8.0 +/- 3.4 units/ml, P < 0.001) and hydroxyl radicals (8.7 +/- 2.5 vs 4.9 +/- 2.3 units/ml, P <0.001) was higher in athletes. Hand SBF after heating and ischemia and foot SBF after heating were higher in athletes (P <0.0001) than in the sedentary group. In the sedentary groups, the lowest tertile of age had higher plasma TOSC values than the highest tertile of age (ROO- 18.2 +/- 2.2 vs 8.8 +/- 1.4 units/ml; HO- 9.2 +/- 1.3 vs 3.7 +/- 0.5 units/ml, P < 0.001). Among athletes, the lowest and the highest tertile of age did not show significantly different plasma TOSC (young: ROO- 20.3 +/- 1.5 and HO-: 9.7 +/- 1.4 units/ml; older: ROO-: 17.1 +/- 1.3 and HO-: 9.0 +/- 0.8 units/ml, n.s.). Resting SBF was similar in all the subgroups; stimulated SBFs were lower in both subgroups of untrained respect to trained individuals (P <0.001). In the sedentary subjects, SBF was inversely related to age (r = -0.63; P <0.0001) and directly related to TOSC against peroxyl (r = 0.59, P <0.001) and hydroxyl radicals (r = 0.47, P <0.01). In athletes SBF was related only to VO2max (r = 0.36; P <0.05) and TOSC vs ROO. (r = 0.41, P <0.01). In conclusion, these results suggest that regular physical activity is associated with a better microvascular endothelial function in older athletes probably due to increased antioxidant defenses.