Pioglitazone and Sodium Salicylate Protect Human β-Cells against Apoptosis and Impaired Function Induced by Glucose and Interleukin-1β

Zeender, E.; Maedler, Kathrin; Bosco, Domenico; Berney, Thierry; Donath, M Y; Halban, Philippe A.

doi:10.1210/jc.2004-0446

Cited by 96 publications

(62 citation statements)

References 71 publications

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“…6). As expected for this population of cells sorted by FACS, most of the cells overexpressing gelsolin were ␤-cells because they also express insulin, as seen after staining with a previously characterized insulin antibody (29).…”

Section: Induction Of Apoptosis In Min6 B1 and C3 Cellssupporting

confidence: 72%

Pro-Survival Role of Gelsolin in Mouse β-Cells

Yermen¹,

Tomás²,

Halban³

2007

Diabetes

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We have previously shown that the Ca 2؉ -dependent actinsevering protein gelsolin plays an important role in regulated insulin secretion. The aim of this study was to determine the role of gelsolin in ␤-cell survival as it has been shown to play a dual role in apoptosis in other cell types. MIN6 subclones B1 and C3, shown previously to express gelsolin at different levels (B1Ͼ ϾC3 cells), were used for this purpose. We demonstrate that B1 cells have lower levels of apoptosis and active caspase-3 when compared with C3 cells, in both standard (25 mmol/l glucose and 15% FCS) and deprived (5 mmol/l glucose and 1% FCS) conditions. Overexpression of gelsolin resulted in a decrease in the percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)

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Section: Induction Of Apoptosis In Min6 B1 and C3 Cellssupporting

confidence: 72%

Pro-Survival Role of Gelsolin in Mouse β-Cells

Yermen¹,

Tomás²,

Halban³

2007

Diabetes

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“…Along with improved glycaemic control and improvements in insulin resistance, beta cell 'rejuvenation' and improvements in beta cell function have been reported in several recent thiazolidinedione trials [40]. In parallel with in vitro data indicating that thiazolidinediones can protect beta cells not only from apoptosis but also from loss of function [41], the role of thiazolidinediones in directly targeting and preserving beta cell function is only now becoming clear [42].…”

Section: Discussionmentioning

confidence: 96%

Effects of rosiglitazone and metformin on pancreatic beta cell gene expression

et al. 2006

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Aims/hypothesis: Rosiglitazone and metformin are two oral antihyperglycaemic drugs used to treat type 2 diabetes. While both drugs have been shown to improve insulin-sensitive glucose uptake, the direct effects of these drugs on pancreatic beta cells is only now beginning to be clarified. The aim of the present study was to determine the direct effects of these agents on beta cell gene expression. Methods: We used reporter gene analysis to examine the effects of rosiglitazone and metformin on the activity of the proinsulin and insulin promoter factor 1 (IPF1) gene promoters in the glucose-responsive mouse beta cell line Min6. Western blot and gel retardation analyses were used to examine the effects of both drugs on the regulation of IPF1 protein production, nuclear accumulation and DNA binding activity in both Min6 cells and isolated rat islets of Langerhans. Results: Over 24 h, rosiglitazone promoted the nuclear accumulation of IPF1 and forkhead homeobox A2 (FOXA2), independently of glucose concentration, and stimulated a two-fold increase in the activity of the Ipf1 gene promoter (p<0.01). Stimulation of the Ipf1 promoter by rosiglitazone was unaffected by the presence of the peroxisome proliferator activated receptor γ antagonist GW9662. No effect of either rosiglitazone or metformin was observed on proinsulin promoter activity. Metformin stimulated IPF1 nuclear accumulation and DNA binding activity in a time-dependent manner, with maximal effects observed after 2 h. Conclusions/interpretation: Metformin and rosiglitazone have direct effects on beta cell gene expression, suggesting that these agents may play a previously unrecognised role in the direct regulation of pancreatic beta cell function.

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“…Another mechanism involves direct actions on pancreatic beta cells [44]. Recent reports have demonstrated that thiazolidinediones directly improve beta cell function [45], ameliorate lipotoxicity [46] and prevent beta cell apoptosis [47,48]. In Wfs1 −/− A y /a mice, direct protective effects, as well as indirect effects, are likely to be exerted.…”

Section: Discussionmentioning

confidence: 99%

Increased insulin demand promotes while pioglitazone prevents pancreatic beta cell apoptosis in Wfs1 knockout mice

et al. 2009

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Aims/hypothesis The WFS1 gene encodes an endoplasmic reticulum (ER) membrane-embedded protein called Wolfram syndrome 1 protein, homozygous mutations of which cause selective beta cell loss in humans. The function(s) of this protein and the mechanism by which the mutations of this gene cause beta cell death are still not fully understood. We hypothesised that increased insulin demand as a result of obesity/insulin resistance causes ER stress in pancreatic beta cells, thereby promoting beta cell death. Methods We studied the effect of breeding Wfs1 −/− mice on a C57BL/6J background with mild obesity and insulin resistance, by introducing the agouti lethal yellow mutation (A y /a). We also treated the mice with pioglitazone.

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Pioglitazone and Sodium Salicylate Protect Human β-Cells against Apoptosis and Impaired Function Induced by Glucose and Interleukin-1β

Cited by 96 publications

References 71 publications

Pro-Survival Role of Gelsolin in Mouse β-Cells

Pro-Survival Role of Gelsolin in Mouse β-Cells

Effects of rosiglitazone and metformin on pancreatic beta cell gene expression

Increased insulin demand promotes while pioglitazone prevents pancreatic beta cell apoptosis in Wfs1 knockout mice

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