BackgroundThere is controversy over whether aerobic or resistance exercise is more effective for improving endothelial function in type 2 diabetes mellitus (T2DM). This study was aimed to investigate the effects of an aerobic and resistance training program on endothelial function, and the influences of glycemic control, body weight changes, and aerobic capacity in T2DM.MethodsTotal 40 overweight women with T2DM were assigned into 3 groups: an aerobic exercise group (AEG, n=13), resistance exercise group (REG, n=12), and control group (CG, n=15), and followed either brisk walking for the AEG or resistance band training for the REG, 60 minutes per day, 5 days per week for 12 weeks with monitoring daily activity using accelerometers. We assessed endothelial function by flow-mediated dilation (FMD), and aerobic capacity by oxygen uptake at anaerobic threshold (AT_VO2) at baseline and following training program.ResultsThe mean participants' age was 57.0±6.8 years, and body mass index (BMI) was 27.0±2.3 kg/m2. After intervention, FMD increased by 2.2±1.9% in AEG, which differed from REG and CG (P=0.002), despite of decreased body weight (BW) in both AG and RG (2.8±2.5%, P=0.002; 1.6±2.0%, P=0.017, respectively). A significant increased AT_VO2 and decreased HbA1c were found only in AEG. In all participants, FMD was changed with the significant relations to the AT_VO2 (r=0.348, P=0.035), but not to HbA1c levels or BW.ConclusionAerobic exercise appears to be more beneficial than resistance exercise for improving endothelial function in T2DM. In addition, aerobic capacity could be a better predictor of changes in FMD than BW and glycemic control.

Aerobic exercise increases sRAGE levels along with improvement of various cardiometabolic risk factors in patients with T2DM.

Leukocyte common antigen-receptor protein tyrosine phosphatases (LAR-RPTPs) are hub proteins that organize excitatory and inhibitory synapse development through binding to various extracellular ligands. Here, we report that knockdown (KD) of the LAR-RPTP family member PTPσ reduced excitatory synapse number and transmission in cultured rat hippocampal neurons, whereas KD of PTPδ produced comparable decreases at inhibitory synapses, in both cases without altering expression levels of interacting proteins. An extensive series of rescue experiments revealed that extracellular interactions of PTPσ with Slitrks are important for excitatory synapse development. These experiments further showed that the intracellular D2 domain of PTPσ is required for induction of heterologous synapse formation by Slitrk1 or TrkC, suggesting that interaction of LAR-RPTPs with distinct intracellular presynaptic proteins, drives presynaptic machinery assembly. Consistent with this, double-KD of liprin-α2 and -α3 or KD of PTPσ substrates (N-cadherin and p250RhoGAP) in neurons inhibited Slitrk6-induced, PTPσ-mediated heterologous synapse formation activity. We propose a synaptogenesis model in presynaptic neurons involving LAR-RPTP-organized retrograde signaling cascades, in which both extracellular and intracellular mechanisms are critical in orchestrating distinct synapse types. In this study, we sought to test the unproven hypothesis that PTPσ and PTPδ are required for excitatory and inhibitory synapse formation/transmission, respectively, in cultured hippocampal neurons, using knockdown-based loss-of-function analyses. We further performed extensive structure-function analyses, focusing on PTPσ-mediated actions, to address the mechanisms of presynaptic assembly at excitatory synaptic sites. Using interdisciplinary approaches, we systematically applied a varied set of PTPσ deletion variants, point mutants, and splice variants to demonstrate that both extracellular and intracellular mechanisms are involved in organizing presynaptic assembly. Strikingly, extracellular interactions of PTPσ with heparan sulfates and Slitrks, intracellular interactions of PTPσ with liprin-α and its associated proteins through the D2 domain, as well as distinct substrates are all critical.

OBJECTIVEWe aimed to evaluate the effects of carnitine-orotate complex in patients with nonalcoholic fatty liver disease (NAFLD) and diabetes. RESEARCH DESIGN AND METHODSEight hospitals in Korea participated in this randomized, controlled, double-blind trial of patients with diabetes and NAFLD. Seventy-eight patients were randomly assigned in a 1:1 ratio to receive carnitine-orotate complex (824 mg, three times daily) or matching placebo. The primary study outcome was decline in alanine aminotransferase (ALT) to the normal range. Secondary study outcomes were change in ALT, radiological hepatic steatosis, parameters for anthropometry, liver function, lipid profiles, and glycemic control. Hepatic steatosis was assessed using Hounsfield units on noncontrast computed tomography (CT) imaging with hepatic attenuation. RESULTSAfter 12 weeks of treatment, compared with placebo group, carnitine-orotate complex-treated participants had a significantly higher rate of normalization of serum ALT level (17.9% vs. 89.7%, P < 0.001). On hepatic CT analysis, participants treated with carnitine-orotate complex showed an increased liver attenuation index (0.74 6 8.05 vs. 6.21 6 8.96, P < 0.008). A significant decrease in HbA 1c was observed in the carnitine-orotate complex group (20.33 6 0.82% [23.6 6 9.0 mmol/mol], P = 0.007), but no significant change was seen in the placebo group. CONCLUSIONSTreatment with carnitine-orotate complex improves serum ALT and may improve hepatic steatosis as assessed by CT in patients with diabetes and NAFLD. Further studies using more advanced magnetic resonance imaging and liver histology as an end point are needed to assess its efficacy in NAFLD.Ectopic fat accumulation in a visceral organ is associated with insulin resistance (1). As an example of such ectopic fat accumulation, nonalcoholic fatty liver disease (NAFLD) is now recognized as the hepatic component of metabolic syndrome and is even reportedly associated with insulin resistance independent of obesity and other metabolic components. Therefore, NAFLD can be a major determinant of insulin