The protective effect of exercise on diabetic nephropathy : the role of histidine-containing dipeptides

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Maize Composites Enhance Economic Returns from Dry Land Farming: Evidences from Uplands of Kashmir Valley

The present study is conducted in dry uplands of Kashmir region to assess the potential of three location-specific maize composites, C6, KG1 and C8 respectively in the Central, South and North regions of Kashmir valley for enhancing the economic returns and sustenance of livelihood of rural masses under the dry land conditions. The study forms part of NAIP project, “Visioning Policy Analysis and Gender (VPAGe)” undertaken at SKUAST-K, Shalimar during 2009-11 and is based on the cross sectional survey data collected from 240 farm households cultivating maize under dry land conditions in the upper belts of Kashmir valley. The adoption of dry land maize composites and its determinants were examined by employing regression function. Economic surplus model and economic feasibility tests were employed to assess the economic gains from research and extension investment involved in the development of maize composites under the study. The bi-variate Probit model was fitted to identify the factors responsible for probability of adoption of maize composites. The study revealed significant yield gains of 32.20, 27.10 and 27.80 q/ha respectively in C6, KG1 and C8 maize composites which increased the marketable surplus significantly. The labour productivity was the highest in C6 followed by C8 and KG1. The net change in partial budget to the tune ` 20,916 per hectare indicated capability of commercial orientation of maize composites and also high B-C ratio of maize composites held the view that maize seed technology could prove a boon for sustenance of farm families of dry lands maize growers in Kashmir valley. The Probit model estimates revealed that the average size of land fragments, educational level, experience of maize growing and yield risk in local varieties were positively significant, while negative significance of average size of land holding suggested that non-fragmentation could help in the adoption of composite maize seed technology. The study concludes that cultivation of maize composites has the potential to secure and sustain livelihood of stake holders under dry land conditions

Has Adoption of Improved Rice Technology Enhanced Economic and Livelihood Security in Kashmir Valley?

The paper has estimated the extent of adoption of an improved rice seed technology in the Kashmir valley and has studied its impact on the economic and the livelihood security of adopters of this technology. The determinants inducing farmers towards adoption of new technology have been identified and technological gaps in its adoption have been estimated. For presenting a comparative picture, 130 adopters and 122 non-adopters of improved technology were identified from six districts , two each from the three regions of Kashmir valley. The study has revealed, based on data collected for the agricultural year 2010- 11 that by adoption of improved technology, both gross returns and net returns have increased considerably, while the cost of production has decreased. The study has clearly brought out that adoption of new technology has provided better economic and livelihood security at the household level in the study area. The age, education and land size have been identified as the major determinants of technology adoption. By presenting statistics obtained through economic surplus model , the study has presented a strong case for higher investments on R&D , extension services delivery and dissemination of improved technology in the Kashmir valley

Diversification of Potassium Currents in Excitable Cells via Kvβ Proteins

Excitable cells of the nervous and cardiovascular systems depend on an assortment of plasmalemmal potassium channels to control diverse cellular functions. Voltage-gated potassium (Kv) channels are central to the feedback control of membrane excitability in these processes due to their activation by depolarized membrane potentials permitting K+ efflux. Accordingly, Kv currents are differentially controlled not only by numerous cellular signaling paradigms that influence channel abundance and shape voltage sensitivity, but also by heteromeric configurations of channel complexes. In this context, we discuss the current knowledge related to how intracellular Kvβ proteins interacting with pore complexes of Shaker-related Kv1 channels may establish a modifiable link between excitability and metabolic state. Past studies in heterologous systems have indicated roles for Kvβ proteins in regulating channel stability, trafficking, subcellular targeting, and gating. More recent works identifying potential in vivo physiologic roles are considered in light of these earlier studies and key gaps in knowledge to be addressed by future research are described

Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk

Carnosine is a naturally occurring dipeptide (β-alanine-L-histidine) which supports physiological homeostasis by buffering intracellular pH, chelating metals, and conjugating with and neutralizing toxic aldehydes such as acrolein. However, it is not clear if carnosine can support cardiovascular function or modify cardiovascular disease (CVD) risk. To examine this, we measured urinary levels of nonconjugated carnosine and its acrolein conjugates (carnosine-propanal and carnosine-propanol) in participants of the Louisville Healthy Heart Study and examined associations with indices of CVD risk. We found that nonconjugated carnosine was significantly associated with hypertension (p = 0.011), heart failure (p = 0.015), those categorized with high CVD risk (p p = 0.007), high sensitivity C-reactive protein (hsCRP; p = 0.026), high-density lipoprotein (HDL; p = 0.007) and certain medication uses. Levels of carnosine-propanal and carnosine-propanol demonstrated significant associations with BMI, blood glucose, HDL and diagnosis of diabetes. Carnosine-propanal was also associated with heart failure (p = 0.045) and hyperlipidemia (p = 0.002), but no associations with myocardial infarction or stroke were identified. We found that the positive associations of carnosine conjugates with diabetes and HDL remain statistically significant (p < 0.05) in an adjusted, linear regression model. These findings suggest that urinary levels of nonconjugated carnosine, carnosine-propanal and carnosine-propanol may be informative biomarkers for the assessment of CVD risk—and particularly reflective of skeletal muscle injury and carnosine depletion in diabetes

Exercise alters and β-alanine combined with exercise augments histidyl dipeptide levels and scavenges lipid peroxidation products in human skeletal muscle

Carnosine and anserine are dipeptides synthesized from histidine and β-alanine by carnosine synthase (ATPGD1). These dipeptides, present in high concentration in the skeletal muscle, form conjugates with lipid peroxidation products such as 4-hydroxy trans-2-nonenal (HNE). Although skeletal muscle levels of these dipeptides could be elevated by feeding β-alanine, it is unclear how these dipeptides and their conjugates are affected by exercise training with or without β-alanine supplementation. We recruited twenty physically active men, who were allocated to either β-alanine or placebo-feeding group matched for VO2 peak, lactate threshold, and maximal power (Wmax). Participants completed 2 weeks of conditioning phase followed by 1 week of exercise testing (CPET) and a single session followed by 6 weeks of high intensity interval training (HIIT). Analysis of muscle biopsies showed that the levels of carnosine and ATPGD1 expression were increased after CPET and decreased following a single session and 6 weeks of HIIT. Expression of ATPGD1 and levels of carnosine were increased upon β-alanine-feeding after CPET, while ATPGD1 expression decreased following a single session of HIIT. The expression of fiber type markers myosin heavy chain (MHC) I and IIa remained unchanged after CPET. Levels of carnosine, anserine, carnosine-HNE, carnosine-propanal and carnosine-propanol were further increased after 9 weeks of β-alanine supplementation and exercise training, but remained unchanged in the placebo-fed group. These results suggest that carnosine levels and ATPGD1 expression fluctuates with different phases of training. Enhancing carnosine levels by β-alanine feeding could facilitate the detoxification of lipid peroxidation products in the human skeletal muscle

Skeletal muscle analysis of cancer patients reveals a potential role for carnosine in muscle wasting

Abstract Background Muscle wasting during cancer cachexia is mediated by protein degradation via autophagy and ubiquitin‐linked proteolysis. These processes are sensitive to changes in intracellular pH ([pH]i) and reactive oxygen species, which in skeletal muscle are partly regulated by histidyl dipeptides, such as carnosine. These dipeptides, synthesized by the enzyme carnosine synthase (CARNS), remove lipid peroxidation‐derived aldehydes, and buffer [pH]i. Nevertheless, their role in muscle wasting has not been studied. Methods Histidyl dipeptides in the rectus abdominis (RA) muscle and red blood cells (RBCs) of male and female controls (n = 37), weight stable (WS: n = 35), and weight losing (WL; n = 30) upper gastrointestinal cancer (UGIC) patients, were profiled by LC–MS/MS. Expression of enzymes and amino acid transporters, involved in carnosine homeostasis, was measured by Western blotting and RT‐PCR. Skeletal muscle myotubes were treated with Lewis lung carcinoma conditioned medium (LLC CM), and β‐alanine to study the effects of enhancing carnosine production on muscle wasting. Results Carnosine was the predominant dipeptide present in the RA muscle. In controls, carnosine levels were higher in men (7.87 ± 1.98 nmol/mg tissue) compared with women (4.73 ± 1.26 nmol/mg tissue; P = 0.002). In men, carnosine was significantly reduced in both the WS (5.92 ± 2.04 nmol/mg tissue, P = 0.009) and WL (6.15 ± 1.90 nmol/mg tissue; P = 0.030) UGIC patients, compared with controls. In women, carnosine was decreased in the WL UGIC (3.42 ± 1.33 nmol/mg tissue; P = 0.050), compared with WS UGIC patients (4.58 ± 1.57 nmol/mg tissue), and controls (P = 0.025). Carnosine was significantly reduced in the combined WL UGIC patients (5.12 ± 2.15 nmol/mg tissue) compared with controls (6.21 ± 2.24 nmol/mg tissue; P = 0.045). Carnosine was also significantly reduced in the RBCs of WL UGIC patients (0.32 ± 0.24 pmol/mg protein), compared with controls (0.49 ± 0.31 pmol/mg protein, P = 0.037) and WS UGIC patients (0.51 ± 0.40 pmol/mg protein, P = 0.042). Depletion of carnosine diminished the aldehyde‐removing ability in the muscle of WL UGIC patients. Carnosine levels were positively associated with decreases in skeletal muscle index in the WL UGIC patients. CARNS expression was decreased in the muscle of WL UGIC patients and myotubes treated with LLC‐CM. Treatment with β‐alanine, a carnosine precursor, enhanced endogenous carnosine production and decreased ubiquitin‐linked protein degradation in LLC‐CM treated myotubes. Conclusions Depletion of carnosine could contribute to muscle wasting in cancer patients by lowering the aldehyde quenching abilities. Synthesis of carnosine by CARNS in myotubes is particularly affected by tumour derived factors and could contribute to carnosine depletion in WL UGIC patients. Increasing carnosine in skeletal muscle may be an effective therapeutic intervention to prevent muscle wasting in cancer patients