Adiponectin Reduces Glucotoxicity-Induced Apoptosis of INS-1 Rat Insulin-Secreting Cells on a Microfluidic Chip

Lin, Pei; Chen, Li; Liu, Dong; Liu, Jinbo; Yang, Nailong; Sun, Yu; Xu, Yuxin; Fu, Yiling; Hou, Xinguo

doi:10.1620/tjem.217.59

Cited by 28 publications

(19 citation statements)

References 23 publications

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“…We also observed a similar protection against glucotoxicity-induced apoptosis by adiponectin. Although two studies have previously reported that adiponectin can be protective against cytokine-, free fatty acid-, and glucotoxicity-induced apoptosis in cultured beta cells (22,29), ours is the first to show such an antiapoptotic property of adiponectin in isolated islets. Cumulatively, these studies and our results suggest that the ability of adiponectin to protect against apoptosis is not isolated to MIN6 beta cells or to serum starvation.…”

Section: Discussioncontrasting

confidence: 43%

“…In cultured beta cells, this increase was apparent in both low and high glucose. In a recently published study a similar increase in Pdx-1 and insulin gene expression was observed in INS-1 cells stimulated with adiponectin during sustained glucotoxicity (29). This increase in insulin gene expression may be a direct effect of Pdx-1 and MafA up-regulation (42) and in turn may have resulted in the adiponectin-induced increase in GSIS.…”

Section: Discussionmentioning

confidence: 52%

“…The impact of adiponectin on insulin secretion in vitro has so far been variable in literature. Upon stimulation with adiponectin, no effect was observed in basal or GSIS from human islets; basal secretion was reduced, whereas GSIS was increased in insulin-resistant mice; GSIS was increased in isolated rat islets; and basal and GSIS was increased during sustained glucotoxicity, and fatty acid-induced inhibition of GSIS was reversed in cultured beta cells (14,16,21,22,29). Therefore, with the human islet study as an exception, there appears to be a general trend for adiponectin to increase GSIS, especially under stressed conditions, such as in insulin resistance, lipotoxicity, glucotoxicity, or serum starvation.…”

Section: Discussionmentioning

confidence: 98%

“…Adiponectin was shown to also have both pro-and antiproliferative effects in numerous cell types mediated by such signaling molecules as AMPK, Akt, and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) (24 -28). Three studies thus far have examined the effects of adiponectin on beta cell viability in vitro: although two show that in a pancreatic beta cell line adiponectin counteracts fatty acid-, cytokine-, and glucotoxicitymediated beta cell apoptosis (22,29), one shows that neither gAd nor fAd has any effect on fatty acid-induced apoptosis in human islets (16). Thus, a clear understanding of the functional role of adiponectin in beta cells and islets is still lacking.…”

mentioning

confidence: 99%

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Adiponectin-induced ERK and Akt Phosphorylation Protects against Pancreatic Beta Cell Apoptosis and Increases Insulin Gene Expression and Secretion*

Wijesekara

Krishnamurthy

Bhattacharjee

et al. 2010

Journal of Biological Chemistry

209

142

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The functional impact of adiponectin on pancreatic beta cells is so far poorly understood. Although adiponectin receptors (AdipoR1/2) were identified, their involvement in adiponectininduced signaling and other molecules involved is not clearly defined. Therefore, we investigated the role of adiponectin in beta cells and the signaling mediators involved. MIN6 beta cells and mouse islets were stimulated with globular (2.5 g/ml) or full-length (5 g/ml) adiponectin under serum starvation, and cell viability, proliferation, apoptosis, insulin gene expression, and secretion were measured. Lysates were subjected to Western blot analysis to determine phosphorylation of AMP-activated protein kinase (AMPK), Akt, or ERK. Functional significance of signaling was confirmed using dominant negative mutants or pharmacological inhibitors. Participation of AdipoRs was assessed by overexpression or siRNA. Adiponectin failed to activate AMPK after 10 min or 1-and 24-h stimulation. ERK was significantly phosphorylated after 24-h treatment with adiponectin, whereas Akt was activated at all time points examined. 24-h stimulation with adiponectin significantly increased cell viability by decreasing cellular apoptosis, and this was prevented by dominant negative Akt, wortmannin (PI3K inhibitor), and U0126 (MEK inhibitor). Moreover, adiponectin regulated insulin gene expression and glucose-stimulated insulin secretion, which was also prevented by wortmannin and U0126 treatment. Interestingly, the data also suggest adiponectin-induced changes in Akt and ERK phosphorylation and caspase-3 may occur independent of the level of AdipoR expression. This study demonstrates a lack of AMPK involvement and implicates Akt and ERK in adiponectin signaling, leading to protection against apoptosis and stimulation of insulin gene expression and secretion in pancreatic beta cells.Type 2 diabetes is characterized by both a loss of insulin sensitivity and beta cell dysfunction in the pancreas. Adiponectin is an adipocyte-derived hormone that shows a strong negative correlation with insulin resistance and obesity (1, 2). Studies show that whereas adiponectin knock-out mice develop insulin resistance and glucose intolerance when challenged with a high fat diet, adiponectin-overexpressing mice are highly insulin-sensitive and are resistant to diet-induced diabetes (3-6). Adiponectin is reported to stimulate fatty acid oxidation and glucose uptake and reduce gluconeogenesis in myocytes and hepatocytes, thus increasing peripheral insulin sensitivity (7). Reduced adiponectin levels are also correlated with reduced vascular function and an increase in coronary artery disease (8).Adiponectin forms trimers or higher order complexes including hexamers and oligomers (9). These higher order complexes of full-length adiponectin (fAd) 4 are the primary circulating forms, and localized proteolytic cleavage of fAd has been shown to produce globular adiponectin (gAd) (10). Two proposed homologous adiponectin receptors (AdipoR1 and AdipoR2) were cloned and shown to be wi...

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Section: Discussioncontrasting

confidence: 43%

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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Adiponectin-induced ERK and Akt Phosphorylation Protects against Pancreatic Beta Cell Apoptosis and Increases Insulin Gene Expression and Secretion*

Wijesekara

Krishnamurthy

Bhattacharjee

et al. 2010

Journal of Biological Chemistry

209

142

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show abstract

“…29 This is supported by observations in INS-1E cells exposed to hyperglycemia and isolated human islets. 19,[30][31][32][33][34] Such downregulation could be due to concomitant reduction in PDX1, which is involved in regulation of insulin gene transcription and expression of other important genes involved in β-cell secretory function. 16 Reduced PDX1 levels have been observed also in HIT-T15 cells, INS-1E cells and human islets treated with high glucose.…”

Section: Discussionmentioning

confidence: 99%

Cellular responses of novel human pancreatic β-cell line, 1.1B4 to hyperglycemia

Vasu

McClenaghan²,

McCluskey

et al. 2013

Islets

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Effect of adiponectin on apoptosis: Proapoptosis or antiapoptosis?

Sun¹,

Chen²

2010

BioFactors

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Adiponectin is a protein hormone mainly secreted by adipose tissue that regulates energy homeostasis and glucose and lipid metabolism. Compared with other adipose-derived hormones, adiponectin is very abundant in plasma and is proposed to be a convenient biomarker for many diseases. A large number of in vitro and in vivo studies support the beneficial effects of adiponectin on metabolic syndrome, diabetes, and atherosclerosis. However, the protective actions were challenged occasionally by the controversies in its role in inflammation and in the specific functions of its different conformations. Recently, quite a few reports suggested that the antiapoptotic activity of adiponectin might contribute to its therapeutic potential during ischemia/reperfusion injury in vivo, whereas some studies demonstrated that adiponectin induced apoptosis both in vitro and in vivo. Herein, this review attempts to summarize the present consensus and divergence and to provide possible alternative and/or complementary explanations for this apparent paradox.

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Adiponectin Reduces Glucotoxicity-Induced Apoptosis of INS-1 Rat Insulin-Secreting Cells on a Microfluidic Chip

Cited by 28 publications

References 23 publications

Adiponectin-induced ERK and Akt Phosphorylation Protects against Pancreatic Beta Cell Apoptosis and Increases Insulin Gene Expression and Secretion*

Adiponectin-induced ERK and Akt Phosphorylation Protects against Pancreatic Beta Cell Apoptosis and Increases Insulin Gene Expression and Secretion*

Cellular responses of novel human pancreatic β-cell line, 1.1B4 to hyperglycemia

Effect of adiponectin on apoptosis: Proapoptosis or antiapoptosis?

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