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BioScientifica

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Published online before print January 24, 2014 , doi: 10.1530/JOE-13-0578

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Abstract

Adiponectin is secreted by the adipose tissue and is downregulated in states of obesity and insulin resistance. There is a growing body of evidence indicating that adiponectin has renoprotective effects and protects against the development of albuminuria in rodent experiments. Adiponectin crossing the glomerular filtration barrier possibly inhibits inflammation, fibrosis and oxidative stress in kidneys through activation of AMP-activated protein kinase. Moreover, microalbuminuria is a well established early sign of progressive cardiovascular and renal disease, even in subjects with preserved glomerular filtration rate. Studies investigating the relationship between serum adiponectin levels and urinary albumin excretion rate (UAE) have yielded conflicting data and the mechanisms underlying the interplay between adiponectin and albuminuria remain to be elucidated. This article constitutes a critical review attempting to clarify any remaining confusion about this matter. Furthermore, this article examines the clinical significance of adiponectin–albuminuria interplay, suggesting that adiponectin is possibly involved in the development of albuminuria that is associated with obesity, diabetes and cardiovascular disease and may mediate, at least in part, the actions of medical treatments that influence UAE, such as angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, thiazolidinediones, fenofibrate and diet. Further studies to investigate more thoroughly the renoprotective role of adiponectin in the human setting should be carefully planned, focusing on causality and the possible influence of adiponectin on the development of albuminuria in specific clinical settings.

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Adiponectin is an adipokine secreted by the adipocytes and downregulated in obesity ( Nicholas Kirkwood Pink Beya Mules GJ6OZ4
). Low levels of circulating adiponectin appear to contribute to the pathophysiology of insulin resistance, type 2 diabetes and cardiovascular disease (CVD) in obese or overweight patients ( Hotta et al . 2000 ). Adiponectin is currently considered to be eliminated through renal biodegradation/excretion, but this mechanism has been proposed mostly on the basis of indirect data ( TAICHI MURAKAMI Platform hi B1UOYf
). Adiponectin has been reported to exert beneficial renal effects, protecting against the development of albuminuria in rodent experiments ( Jimmy choo Suede Logo Bow Gleam Flats riWEdL
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). Adiponectin has been shown to have anti-inflammatory, antifibrotic and antioxidant effects on kidneys through AMP-activated protein kinase (AMPK) activation. The influence of adiponectin on the development of albuminuria appears to have high clinical significance, because microalbuminuria constitutes an early sign of progressive cardiovascular and renal diseases in subjects with and without diabetes ( de Jong Curhan 2006 ). At the time that microalbuminuria develops the glomerular filtration rate (GFR) is typically normal or only modestly elevated. In addition, the development of albuminuria can be associated with minimal structural glomerular changes but without any significant change in renal haemodynamics.

The characterization of this population of NSZO backcross mice that had been fed on a fat-enriched diet will be reported elsewhere by our group ( Christian Louboutin Velvet Sandals Dta9XqH
). For the purpose of this study, three groups (normoglycemic, hyperinsulinemic, and diabetic) of selected animals were assembled according to their metabolic parameters. In addition, NSZO mice were fed on a standard diet, and one group of both males and females that were of normal blood glucose and plasma insulin were selected to test for diet effects. Table Replay DAWSON Trainers navy uXsy867
summarizes the body weight and metabolic parameters measured in the NSZO mice that where selected for the present study.

The concentration of plasma FFAs, which are known inducers of certain P450 isoforms (e.g., CYP4A subfamily) ( Ancient Greek Sandals Niki Sandals in IycmbRuV
; Zangar and Novak, 1997 ), is also shown in Table 1 . As expected, a significant increase in plasma FFAs was observed with a fat-enriched diet in both sexes (males, p = 0.004; females, p = 0.001). Hyperinsulinemia significantly reduced the concentration of FFAs in the plasma in males ( p = 0.018) but failed to do so in female mice ( p = 0.213). The level of FFAs in the plasma was the same between males and females when maintained on a fat-enriched diet. On a standard diet, the level of FFAs in the plasma of male mice was greater than in females.

The data obtained from hybridization of P450 probes to Northern blots of pooled RNA and dot blots of RNA from individuals from each group are presented in Table Sebastian Cross strap platform sandals MQn9b7wJ
and Figs. Giuseppe Zanotti Meredith pumps 5uq8DGIPf
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. From these results, it was possible to distinguish three groups of the investigated P450 isoforms according to their response to diabetes or hyperinsulinemia. The first group showed an increase in P450 expression in the liver of diabetic NSZO backcross mice. It also showed a slight increase, or no change, in expression in the liver of hyperinsulinemic animals. This pattern of expression was found for the female-specific isoforms Cyp2b9 and Cyp3a16 and also for Cyp4a14 , which is involved in fatty acid oxidation and known to be induced by PPARα ( Kroetz et al., 1998 ; Enriquez et al., 1999 ) (Table 3 ; Fig. 1 ).

View this table:
Table 3

Patterns of regulation of P450 and GST mRNA with regard to glycemic status, sex, and diet

Figure 1

Analysis of P450 expression in normoglycemic (N), diabetic (D), and hyperglycemic (H) NSZO mice fed on a fat-enriched or standard diet. Animals maintained on standard diet were of normal glucose status. Northern blots of pooled hepatic RNA from individuals from each group and bar diagrams from dot-blot analyses of individual animals from each group are shown. Data are expressed as a percentage relative to the male high-fat normoglycemic group (mean ± S.E.).

Figure 2

Analysis of expression in normoglycemic (N), diabetic (D), and hyperglycemic (H) NSZO mice fed on a fat-enriched or standard diet. Animals maintained on standard diet were of normal glucose status. Northern blots of pooled hepatic RNA from individuals from each group and bar diagrams from dot-blot analyses of individual animals from each group are shown. Data are expressed as a percentage relative to the male high-fat normoglycemic group (mean ± S.E.).

The level of Cyp2c22 mRNA was found to follow the second pattern of expression, with the level of this isoform dramatically decreased in the liver of diabetic mice (Fig. Salvatore Ferragamo Cloth Heels YnPU0Gdmk
). A smaller decrease in male hyperinsulinemic mice compared with males of normal glycemic status was also detected; however, this was not reflected in hyperinsulinemic females. This striking effect of diabetes on the expression of Cyp2c22 prompted a more thorough investigation into the effect of diabetes and hyperinsulinemia on expression of the Cyp2c subfamily in general. Therefore, the mRNA levels of Cyp2c29 , Cyp2c39 , Cyp2c40 , and the putative mouse Cyp2c23 were examined. A down-regulation was also observed for Cyp2c29 and Cyp2c40 in diabetic mice, however, the degree of decrease for these two transcripts was not as great as that found for Cyp2c22 (Fig. 2 ). Two main bands were detected in Northern-blot analysis of Cyp2c39 and the pattern of expression was found to be similar to that observed for Cyp2c29 (results not shown). Cyp2c29 and Cyp2c39 mRNA are 88% identical in the nucleotide sequence, and therefore the main band detected with both probes on the Northern blot was considered to represent Cyp2c29 mRNA. This conclusion was based on the fact that a database search revealed around 20-fold more expressed sequence tags (ESTs) for Cyp2c29 , suggesting that Cyp2c39 is expressed at a much lower level. Cyp2c23 was found to be highly variable among individual animals within all groups.

Our hunt for inner work life triggers led us to the progress principle. When we compared our research participants’ best and worst days (based on their overall mood, specific emotions, and motivation levels), we found that the most common event triggering a “best day” was any progress in the work by the individual or the team. The most common event triggering a “worst day” was a setback.

Consider, for example, how progress relates to one component of inner work life: overall mood ratings. Steps forward occurred on 76% of people’s best-mood days. By contrast, setbacks occurred on only 13% of those days. (See the exhibit “What Happens on a Good Day?”)

Progress—even a small step forward—occurs on many of the days people report being in a good mood.

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Two other types of inner work life triggers also occur frequently on best days: Catalysts , actions that directly support work, including help from a person or group, and nourishers , events such as shows of respect and words of encouragement. Each has an opposite: Inhibitors , actions that fail to support or actively hinder work, and toxins , discouraging or undermining events. Whereas catalysts and inhibitors are directed at the project, nourishers and toxins are directed at the person. Like setbacks, inhibitors and toxins are rare on days of great inner work life.

Events on worst-mood days are nearly the mirror image of those on best-mood days (see the exhibit “What Happens on a Bad Day?”). Here, setbacks predominated, occurring on 67% of those days; progress occurred on only 25% of them. Inhibitors and toxins also marked many worst-mood days, and catalysts and nourishers were rare.

Events on bad days—setbacks and other hindrances—are nearly the mirror image of those on good days.

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This is the progress principle made visible: If a person is motivated and happy at the end of the workday, it’s a good bet that he or she made some progress. If the person drags out of the office disengaged and joyless, a setback is most likely to blame.

When we analyzed all 12,000 daily surveys filled out by our participants, we discovered that progress and setbacks influence all three aspects of inner work life. On days when they made progress, our participants reported more positive emotions . They not only were in a more upbeat mood in general but also expressed more joy, warmth, and pride. When they suffered setbacks, they experienced more frustration, fear, and sadness.

Motivations were also affected: On progress days, people were more intrinsically motivated—by interest in and enjoyment of the work itself. On setback days, they were not only less intrinsically motivated but also less extrinsically motivated by recognition. Apparently, setbacks can lead a person to feel generally apathetic and disinclined to do the work at all.

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Executive Summary

When you ask workers what matters to them, respect from superiors often tops the list. Yet employees report more disrespectful and uncivil behavior each year. This disconnect happens in large part because leaders have an incomplete understanding of what constitutes workplace respect—and so even well-meaning efforts to provide it often fall short.

The author’s research shows that employees value two distinct types of respect. is accorded equally to all members of a work group or organization. It’s signaled by civility and an atmosphere suggesting that every member is inherently valuable. recognizes individual employees who display valued qualities or behaviors.

To better understand the two types of respect, the author spent 15 months studying a unique work program for female prison inmates—a context that sharply highlights the differences between a respectful environment and a disrespectful one. At Televerde, a B2B marketing firm, regular displays of owed and earned respect have created an extraordinarily engaged workforce responsible for impressive profitability and growth, and recidivism among Televerde’s inmate employees is 80% lower than the national average.

Although Televerde operates in an unusual context, its employees’ need for respect is universal. The author details seven ways in which leaders and managers can convey owed and earned respect and thus build a workplace that allows employees—and, as a result, their companies—to become the best possible versions of themselves.

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The Deficit

A respectful workplace brings enormous benefits to organizations, but efforts to provide one often fall short. That’s partly because leaders have an incomplete understanding of respect.

The Fix

Research shows that employees value two distinct types of respect. is accorded equally to all members of a work group or an organization. recognizes individuals who display valued qualities or behaviors and acknowledges that each employee has specific strengths and talents.

The Idea in Practice

At Televerde, a technology-focused B2B marketing firm staffed by female prison inmates, regular displays of owed and earned respect have created an extraordinarily engaged workforce responsible for impressive profitability and growth. And recidivism among Televerde’s inmate employees is 80% lower than the national rate.

When you ask workers what matters most to them, feeling respected by superiors often tops the list. In a recent survey by Georgetown University’s Christine Porath of nearly 20,000 employees worldwide, respondents ranked respect as the most important leadership behavior. Yet Golden GooseMens Slide Sneaker SdJ2pUy
more disrespectful and uncivil behavior each year.

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