Tissue-specific expression and regulation of GSK-3 in human skeletal muscle and adipose tissue

Ciaraldi, Theodore P.; Oh, Deborah K.; Christiansen, Louis; Nikoulina, Svetlana E.; Kong, Alice P.S.; Baxi, Sunita; Mudaliar, Sunder; Henry, Robert R.

doi:10.1152/ajpendo.00176.2006

Cited by 42 publications

(38 citation statements)

References 40 publications

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“…In 13 (8 T2D AND 5 ND) subjects, paired samples of SAT and VAT were obtained. SAT was also obtained from 24 obese subjects (13 T2D and 11 ND) by needle biopsy as previously described (11).…”

Section: Methodsmentioning

confidence: 99%

Adiponectin secretion and response to pioglitazone is depot dependent in cultured human adipose tissue

Phillips

Ciaraldi²,

Oh³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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To test the hypothesis that depot differences exist for adiponectin, fresh and cultured human VAT and SAT from obese type 2 diabetic (T2D) and obese nondiabetic (ND) subjects was examined to determine whether differences in adiponectin content and secretion occurred as a function of depot studied, diabetic status, and response to thiazolidinedione treatment. VAT and SAT were obtained by biopsy and AT explants cultured in defined media for 7 days. Protein expression was assessed by Western blot. Adiponectin content of conditioned medium was determined by radioimmunoassay. Diabetic status had no effect on adiponectin secretion over days 0 -2 of culture. In ND SAT, secretion fell over days 2-4 but was sustained at greater levels vs. T2D SAT. In both ND and T2D VAT, adiponectin secretion was low, similar to T2D SAT. Over the 7-day culture period, cellular adiponectin increased in ND SAT and VAT; it remained unchanged in T2D SAT and VAT. Pioglitazone increased adiponectin secretion and content in all SAT. Pioglitazone failed to increase adiponectin secretion from either ND or T2D VAT and increased cellular content only in ND VAT. AT depot differences exist in the secretion of adiponectin and responsiveness to thiazolidinedione treatment. These data suggest that SAT, not VAT, appears to be the major contributor to increased circulating adipopnectin levels in response to pioglitazone treatment. adipose tissue physiology; type 2 diabetes mellitus; body fat distribution; thiazolidinediones; leptin ADIPOSE TISSUE (AT) is recognized to play an important role in the regulation of lipid/carbohydrate metabolism, energy homeostasis, and insulin sensitivity (55) via release of metabolically active products that regulate insulin sensitivity and fat metabolism (27). Many AT products exert opposing actions on insulin sensitivity, inflammation, and fatty acid metabolism. For example, AT products IL-6, TNF-␣, and resistin may impair insulin sensitivity, increase circulating free fatty acids, and exert proinflammatory effects, whereas others such as adiponectin exert insulin-sensitizing effects, reduce free fatty acids, and dampen inflammation (28). The metabolic impact of a given AT depot is therefore related to the relative profile or balance of mediator release.AT is distributed to a variety of locations, and in humans contributions of SAT and VAT can be distinguished (reviewed in Ref. 59). Individuals with increased visceral (V)AT are at higher risk of developing the metabolic syndrome, type 2 diabetes (T2D), and cardiovascular disease (32, 59) than those with similar amounts of AT as subcutaneous (S)AT (34). Underlying these findings are depot differences in gene and protein expression (36, 37). These findings lend support to the idea that different AT depots are functionally distinct metabolic units.Circulating levels of adiponectin are low in obese and insulin-resistant subjects (62) and are predictive for development of T2D (30). In contrast, adiponectin is high in lean and insulin-sensitive subjects (50). Interestingly, seru...

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Section: Methodsmentioning

confidence: 99%

Adiponectin secretion and response to pioglitazone is depot dependent in cultured human adipose tissue

Phillips

Ciaraldi²,

Oh³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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“…GSK-3 is a serine/ threonine protein kinase first identified by its ability to phosphorylate and inactivate glycogen synthase, the rate-limiting enzyme in glycogen synthesis (39), with important roles in the regulation of glycogen synthesis. Insulin administration results in serine phosphorylation and thus inactivation of GSK-3, thereby leading to an increase in glycogen synthase activity (40). However, oxidative stress-induced reduced Akt/protein kinase B phosphorylation leads to impaired phosphorylation of GSK, followed by suppressed glycogen synthase activity, resulting in decreased glycogen synthesis.…”

Section: Mapkmentioning

confidence: 99%

The Effects of Palmitate on Hepatic Insulin Resistance Are Mediated by NADPH Oxidase 3-derived Reactive Oxygen Species through JNK and p38MAPK Pathways

Gao

Nong

Huang

et al. 2010

Journal of Biological Chemistry

283

229

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Elevated plasma free fatty acid (FFA) levels in obesity may play a pathogenic role in the development of insulin resistance. However, molecular mechanisms linking FFA to insulin resistance remain poorly understood. Oxidative stress acts as a link between FFA and hepatic insulin resistance. NADPH oxidase 3 (NOX3)-derived reactive oxygen species (ROS) may mediate the effect of TNF-␣ on hepatocytes, in particular the drop in cellular glycogen content. In the present study, we define the critical role of NOX3-derived ROS in insulin resistance in db/db mice and HepG2 cells treated with palmitate. The db/db mice displayed increased serum FFA levels, excess generation of ROS, and upregulation of NOX3 expression, accompanied by increased lipid accumulation and impaired glycogen content in the liver. Similar results were obtained from palmitate-treated HepG2 cells. The exposure of palmitate elevated ROS production and NOX3 expression and, in turn, increased gluconeogenesis and reduced glycogen content in HepG2 cells. We found that palmitate induced hepatic insulin resistance through JNK and p38 MAPK pathways, which are rescued by siRNA-mediated NOX3 reduction. In conclusion, our data demonstrate a critical role of NOX3-derived ROS in palmitate-induced insulin resistance in hepatocytes, indicating that NOX3 is the predominant source of palmitate-induced ROS generation and that NOX3-derived ROS may drive palmitate-induced hepatic insulin resistance through JNK and p38 MAPK pathways.

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“…Table 1 summaries some of the most important signaling molecules involved in CR-induced biological and physiological responses. FOXO ↓ [89,97] GSK-3β ↓ [93,98] HIF-1 ↓ [95,99] HSF-1 ↑ [94] HSP-70 ↑ [94,100] mTOR ↓ [90,101] NF-κB ↓ [81,82,95,97] PGC-1α ↑ [91,92] PPAR α ↑ [91,102] SIRT1 ↑↓ [92,93,103] ↑=increase in signal transduction; ↓=decrease in signal transduction.…”

Section: Signal Transduction Mechanism Involved In Crmentioning

confidence: 99%

Caloric restriction and heart function: is there a sensible link?

Han

Ren

2010

Acta Pharmacol Sin

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Calorie restriction (CR) is defined as a reduction in calorie intake below the usual ad libitum intake without malnutrition. In general, the daily caloric intake subjected to CR has been restricted to 50% to 70% of the average food intake in subjects eating ad libitum [1,2] . CR was first reported to retard aging and prolong median and maximal life span in the 1930s [3] . Over the last several decades, CR has been widely studied which exhibits an apparent beneficial impact on longevity, ageassociated diseases, and attenuation of functional decline, across a broad variety of species (including rats, mice, fish, flies, worms and yeast) [4,5] . Moreover, CR provides protection against a cadre of chronic diseases including diabetes mellitus, neurodegenerative diseases, autoimmune disorders [6][7][8] and cancer [9][10][11][12] . CR has been shown to alter a variety of physiological parameters especially reduced metabolic rate and oxidative damage, resulting in a decrease in the incidence of cardiovascular diseases [13] . In response to energy deficiency, experimental animals experience a drastic decrease in both fat mass and lean body mass. Muscle mass is overtly reduced, although the rate of loss of function and mass/body weight with the aging process is attenuated [9,[14][15][16] . Metabolic rate may decrease transiently although studies have indicated similar metabolic rate per kg lean body mass to that of ad libitum fed rodents in longterm CR protocol [17] . Body temperature, systolic and diastolic blood pressure all decrease [18,19] along with the reduced sympathetic activity [20] . CR-treated animals are more spontaneously active and display superior cognitive abilities compared to their ad libitum counterparts [21,22] .The most prominent mechanism that may be responsible for the beneficial health and physiological effects of CR are usually mediated through increased insulin sensitivity which results in reduced plasma glucose and insulin concentrations and improved glucose tolerance [23] ; reduced levels of oxidative stress (decreased oxidative damage to proteins, lipids and DNA) [24] , increased resistance to various types of stress including heat, oxidative and metabolic stress [25] as well as enhanced immune function [26] . Impact of CR on agingAn inverse relationship between calorie intake and lifespan has been revealed in mice, suggesting a key role for regulators of energy metabolism in the mechanism of CR. Accordingly, CR-induced metabolic reprogramming may be a key event in the mechanism of lifespan extension [27,28] . The age when CR is started, the severity of restriction, and strain or genetic background of animals determine the magnitude of life extension. The only mammals in which CR has clearly been shown ReviewCaloric restriction and heart function: is there a sensible link? Calorie restriction (CR) is defined as a reduction in calorie intake below the usual ad libitum intake without malnutrition. Ample of clinical and experimental evidence has demonstrated that CR is capable of retarding aging p...

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Tissue-specific expression and regulation of GSK-3 in human skeletal muscle and adipose tissue

Cited by 42 publications

References 40 publications

Adiponectin secretion and response to pioglitazone is depot dependent in cultured human adipose tissue

Adiponectin secretion and response to pioglitazone is depot dependent in cultured human adipose tissue

The Effects of Palmitate on Hepatic Insulin Resistance Are Mediated by NADPH Oxidase 3-derived Reactive Oxygen Species through JNK and p38MAPK Pathways

Caloric restriction and heart function: is there a sensible link?

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