Alterations in the Hemato-biochemical, Endocrine, Somatic Cell Count and Milk Composition in Lactating Tarai Buffaloes during Different Lactation Stages

Background: Tarai buffalo is indigenous buffalo breed of Uttarakhand state, dual purpose, well adapt to hot-humid climatic condition of Tarai area. This study aimed to evaluate the alterations in the hemato-biochemical, endocrine, milk somatic cell count and milk composition in lactating Tarai buffaloes. Methods: Thirty-six healthy Tarai buffaloes were selected from four different Gujjar farms and divided into four groups consisting nine buffaloes in each group as early (60±30 days), mid (120±30 days) and late (180±30 days) lactation stages and dry buffaloes. Both blood and milk samples were collected once from each lactation stage of selected animals. Hematological parameters and milk composition were evaluated by standard procedures and methods. Biochemical and endocrine parameters were evaluated using commercially available kits as per manufacturer’s protocol. Milk somatic cell count (SCC) was done by direct microscopic counts using Newman Lampert stain. Result: It observed significantly (p less than 0.05) higher TLC value but lower plasma glucose, cholesterol, calcium, phosphorus and urea levels during early lactation stage. Significantly (p less than 0.05) declined in plasma total protein during late lactation stage and triglyceride in dry cows. Plasma hormone significantly (p less than 0.05) higher in cortisol during early lactation while higher T4 and insulin in late lactation stages. Milk fat, urea and total solids were significantly (p less than 0.05) decreased during early lactation and again increased during late lactation while milk SCC significantly (p less than 0.05) higher during early and late lactation stages.

Postprandial dynamics of proglucagon cleavage products and their relation to metabolic health

While oral glucose ingestion typically leads to a decrease in circulating glucagon levels, a substantial number of persons display stable or rising glucagon concentrations when assessed by radioimmunoassay (RIA). However, these assays show cross-reactivity to other proglucagon cleavage products. Recently, more specific assays became available, therefore we systematically assessed glucagon and other proglucagon cleavage products and their relation to metabolic health. We used samples from 52 oral glucose tolerance tests (OGTT) that were randomly selected from an extensively phenotyped study cohort. Glucagon concentrations quantified with RIA were non-suppressed at 2 hours of the OGTT in 36 % of the samples. Non-suppressors showed lower fasting glucagon levels compared to suppressors (p=0.011). Similar to RIA measurements, ELISA-derived fasting glucagon was lower in non-suppressors (p<0.001). Glucagon 1-61 as well as glicentin kinetics were significantly different between suppressors and non-suppressors (p=0.004 and p=0.002, respectively) with higher concentrations of both hormones in non-suppressors. Levels of insulin, C-peptide, and free fatty acids were comparable between groups. Non-suppressors were leaner and had lower plasma glucose concentrations (p=0.03 and p=0.047, respectively). Despite comparable liver fat content and insulin sensitivity (p≥0.3), they had lower 2-hour post-challenge glucose (p=0.01). Glucagon 1-61, glicentin and GLP-1 partially account for RIA-derived glucagon measurements due to cross-reactivity of the assay. However, this contribution is small, since the investigated proglucagon cleavage products contribute less than 10% to the variation in RIA measured glucagon. Altered glucagon levels and higher post-challenge incretins are associated with a healthier metabolic phenotype that is known to be indicative for reduced cardiovascular risk, cancer incidence, and mortality.

SGLT2 Inhibitors: Physiology and Pharmacology

SGLTs are sodium glucose transporters found on the luminal membrane of the proximal tubule, where they reabsorb some 180 grams (one mole) of glucose from the glomerular filtrate each day. The natural glucoside phlorizin completely blocks glucose reabsorption. Oral SGLT2 inhibitors are rapidly absorbed into the blood stream where they remain in in the circulation for hours. On glomerular filtration, they bind specifically to SGLT2 in the luminal membrane of the early proximal tubule to reduce glucose reabsorption by 50-60%. Because of glucose excretion, these drugs lower plasma glucose and glycosylated hemoglobin levels in patients with type 2 diabetes mellitus. The drugs also protect against heart and renal failure. The aim of this review is to summarize what is currently known about the physiology of renal SGLTs and the pharmacology of SGLT drugs.

Ventricular-arterial coupling as a potential therapeutic target in diabetes

Patients with type 2 diabetes (T2D) are at high risk of cardiovascular complications. Novel anti-diabetic medications such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to possess cardiac and renal protective effects beyond their ability to lower plasma glucose. Use of SGLT-2i and GLP-1RA in patients with T2D and heart failure reduce cardiovascular risk and heart failure related hospitalizations. SGLT-2i treatment has shown to improve the long-term prognosis of patients with heart failure. Both drugs also have the potential to normalize ventricular-arterial coupling (VAC). VAC is the crosstalk between the left ventricular function and the arterial system, and is an indicator of the global cardiovascular performance. In this overview, we will describe the concept of VAC and the features of diabetic cardiomyopathy, as well as VAC as a potential therapeutic target in diabetes by use of novel anti-diabetic drugs, primarily SGLT-2i and GLP-1RA. Continuous...

Discovery through Machine Learning and Preclinical Validation of Novel Anti-Diabetic Peptides

While there have been significant advances in drug discovery for diabetes mellitus over the past couple of decades, there is an opportunity and need for improved therapies. While type 2 diabetic patients better manage their illness, many of the therapeutics in this area are peptide hormones with lengthy sequences and a molecular structure that makes them challenging and expensive to produce. Using machine learning, we present novel anti-diabetic peptides which are less than 16 amino acids in length, distinct from human signalling peptides. We validate the capacity of these peptides to stimulate glucose uptake and Glucose transporter type 4 (GLUT4) translocation in vitro. In obese insulin-resistant mice, predicted peptides significantly lower plasma glucose, reduce glycated haemoglobin and even improve hepatic steatosis when compared to treatments currently in use in a clinical setting. These unoptimised, linear peptides represent promising candidates for blood glucose regulation which require further evaluation. Further, this indicates that perhaps we have overlooked the class of natural short linear peptides, which usually come with an excellent safety profile, as therapeutic modalities.

Early Growth and Protein-Energy Metabolism in Chicken Lines Divergently Selected on Ultimate pH

In chickens, a divergent selection on the Pectoralis major pHu allowed the creation of the pHu+ and pHu− lines, which represent a unique model for studying the biological control of carbohydrate storage in muscle. The present study aimed to describe the early mechanisms involved in the establishment of pHu+ and pHu− phenotypes. At hatching, pHu+ chicks were slightly heavier but exhibited lower plasma glucose and triglyceride and higher uric acid. After 5 days, pHu+ chicks exhibited higher breast meat yield compared to pHu− while their body weight was no different. At both ages, in vivo muscle glycogen content was lower in pHu+ than in pHu− muscles. The lower ability of pHu+ chicks to store carbohydrate in their muscle was associated with the increased expression of SLC2A1 and SLC2A3 genes coding glucose transporters 1 and 3, and of CS and LDHα coding key enzymes of oxidative and glycolytic pathways, respectively. Reduced muscle glycogen content at hatching of the pHu+ was concomitant with higher activation by phosphorylation of S6 kinase 1/ribosomal protein S6 pathway, known to activate protein synthesis in chicken muscle. In conclusion, differences observed in muscle at slaughter age in the pHu+ and pHu− lines are already present at hatching. They are associated with several changes related to both carbohydrate and protein metabolism, which are likely to affect their ability to use eggs or exogenous nutrients for muscle growth or energy storage.

Nocturnal One-Hour Lighting Stimulates Gonadal Development and Lowers Fat Deposition in Male Mule Ducks

In this study, the effects of a nocturnal light pulse on body weight, organ mass, gonadal function, and plasma levels of metabolites were determined in male mule ducks. In total, 32 15-week-old mule ducks were randomly allocated to either Group C (control group) or L+ (lighting group). Group C was exposed to the natural photoperiod, whereas Group L+ was provided with a 1-h lighting over 20:00–21:00 every day, in addition to the natural photoperiod. At the end of the 42-day experiment, Group L+ had significantly lower relative weights (% of live weight) of the digestive tract and abdominal fat and higher relative weights of the breast meat and testes than Group C. Moreover, Group L+ had significantly higher plasma testosterone and lower plasma glucose levels. However, no between-group differences were observed in the triacylglycerol and uric acid levels. Histological examination demonstrated that the seminiferous tubule diameter was larger in Group L+ than in Group C. Moreover, the meiosis stage in spermatogenesis had begun in Group L+ but not in Group C. In conclusion, the supplemented 1-h lighting at 20:00 stimulated gonadal development and function and reduced fat deposition.

Sex-specific differences in physiological recovery and short-term behaviour following fisheries capture in adult sockeye salmon (Oncorhynchus nerka)

Numerous laboratory and field studies have found that female Pacific salmon have higher mortality than males during their once-in-a-lifetime upriver spawning migration. However, the proximate cause(s) of this increased mortality are poorly understood. This study exposed sockeye salmon (Oncorhynchus nerka) to a mild capture and tagging stressor and evaluated physiological recovery and movement behaviour at 1 and 4 h postrelease. Female sockeye salmon did not expend more anaerobic energy in response to the stressor but did have higher plasma lactate levels 4 h after the stressor, indicating that females took longer to physiologically recover compared with males. In addition, female salmon had lower plasma glucose but higher plasma cortisol, plasma K+, and cardiac lactate levels compared with males. Male and female salmon had markedly different postrelease behaviours within the first hour of release; males were more likely to hold position within the staging area. Two potential mechanisms leading to increased mortality in female salmon were identified in this study: (a) prolonged recovery duration (possibly mediated by elevated plasma cortisol levels) and (b) insufficient oxygen delivery to the heart.

Plasma glucose levels in the association between serum trans-β-carotene and obesity among children and adolescents

Background Results on the association between trans-β-carotene and obesity are less clear and little is known about how their relationship may be affected by plasma glucose levels.The present study aimed to evaluate the relationships between trans-β-carotene and obesity and to investigate whether plasma glucose levels had a modifying effect on these relationships. Methods Children aged 6-18 years were selected from the National Health and Nutrition Examination Survey(NHANES) (2001–2006) (n =8030). The serum trans-β-carotene levels were divided into tertiles, and their associations with obesity were evaluated using multivariable-adjusted linear regression models adjusted for potential confounding factors. The interaction effects between trans-β-carotene levels and plasma glucose levels on obesity were further evaluated. Results In the fully adjusted model, using serum trans-β-carotene as natural log-transformed continuous variable, the negative association between trans-β-carotene level and obesity were confirmed. In addition, plasma glucose levels significantly modified the inverse association between trans-β-carotene and obesity (p value for interaction: 0.09). A stronger association of trans-β-carotene levels with obesity was found in higher plasma glucose levels (more than100 mg/dl) than in lower plasma glucose levels. Further, a non-linear relationship was detected between trans-β-carotene and obesity in participants with higher plasma glucose levels, with an inflection point of 2.7 (trans-β-carotene =14.88 ug/dl). The effect sizes and confidence intervals for the left and right sides of the inflection point were 0.10 (0.00 to 0.2) and 6.7 (0.1 to 348.2), respectively. Conclusion Our findings indicate that the association between trans-β-carotene concentration and obesity is stronger in individuals with higher plasma glucose population than in those with lower plasma glucose levels.

Intake of Molecular Hydrogen in Drinking Water Increases Membrane Transporters, p-Glycoprotein, and Multidrug Resistance-Associated Protein 2 without Affecting Xenobiotic-Metabolizing Enzymes in Rat Liver

Molecular hydrogen (H2) has been shown to have antioxidant and anti-inflammatory activities that may reduce the development and progression of many diseases. In this study, hydrogen-rich water (HRW) was obtained by reacting hybrid magnesium–carbon hydrogen storage materials with water. Then, the effects of intake of HRW on the activities of xenobiotic-metabolizing enzymes, membrane transporters, and oxidative stress in rats were investigated. Rats were given HRW ad libitum for four weeks. The results showed that intake of HRW had no significant effect on the activities of various cytochrome P450 (CYP) enzymes (CYP1A1, 1A2, 2B, 2C, 2D, 2E1, 3A, and 4A), glutathione-S-transferase, and Uridine 5′-diphospho (UDP)-glucuronosyltransferase. Except for a mild lower plasma glucose concentration, intake of HRW had no effect on other plasma biochemical parameters in rats. p-Glycoprotein and multidrug resistance-associated protein (Mrp) 2 protein expressions in liver were elevated after intake of HRW. However, HRW had no significant effects on glutathione, glutathione peroxidase, or lipid peroxidation in liver. The results from this study suggest that consumption of HRW may not affect xenobiotic metabolism or oxidative stress in liver. However, intake of HRW may increase the efflux of xenobiotics or toxic substances from the liver into bile by enhancing p-glycoprotein and Mrp2 protein expressions.