Role of caspases in the regulation of apoptotic pancreatic islet beta‐cells death

Hui, Hongxiang; Dotta, Francesco; Mario, U. Di; Perfetti, Riccardo

doi:10.1002/jcp.20021

Cited by 95 publications

(87 citation statements)

References 250 publications

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“…The final steps resulting in apoptosis involve both endoplasmic reticulum stress (37) and mitochondrial disruption (38). Glucose toxicity has also been associated with intrinsic pathways involving Bad and Bid that converge on mitochondrial disruption (39). Reductions in cytochrome c release and caspase 9 activation, key components of apoptosis associated with mitochondrial disruption, are probable consequences of the regulation of Bax expression by GIP.…”

Section: Discussionmentioning

confidence: 99%

Glucose-dependent Insulinotropic Polypeptide (GIP) Stimulation of Pancreatic β-Cell Survival Is Dependent upon Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (PKB) Signaling, Inactivation of the Forkhead Transcription Factor Foxo1, and Down-regulation of bax Expression

Kim

Winter

Nian

et al. 2005

Journal of Biological Chemistry

221

142

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Section: Discussionmentioning

confidence: 99%

Glucose-dependent Insulinotropic Polypeptide (GIP) Stimulation of Pancreatic β-Cell Survival Is Dependent upon Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (PKB) Signaling, Inactivation of the Forkhead Transcription Factor Foxo1, and Down-regulation of bax Expression

Kim

Winter

Nian

et al. 2005

Journal of Biological Chemistry

221

142

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“…The loss of islet beta cells through apoptosis (programmed cell death) is a cause of type 1 and type 2 diabetes (for review see [23]). Members of the TGF-β superfamily, particularly activins, have been implicated in regulating islet beta cell apoptosis as well as proliferation, differentiation and other functions [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Activin receptor-like kinase 7 induces apoptosis of pancreatic beta cells and beta cell lines

Zhang

Kumar

et al. 2006

Diabetologia

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Aims/hypothesis: Activin receptor-like kinase 7 (ALK7), a member of the type I receptor serine/threonine kinases of the TGF-β superfamily, was recently reported to regulate cell proliferation and apoptosis. We hypothesised that ALK7 may play a role in modulating pancreatic beta cell proliferation and/or apoptosis. Methods: We detected ALK7 expression in beta cells using RT-PCR, immunostaining and western blotting. Constitutively active, dominant negative or wild-type ALK7 was introduced into beta cells using adenoviral delivery. Proliferation was assessed using 3 H-thymidine incorporation and apoptosis was quantified using terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling detection, DNA degradation analysis and caspase-3 assays. Results: Induction of constitutively active ALK7 in beta cells resulted in growth inhibition and enhanced apoptosis; no effect was seen with INS-1 cells expressing wild-type or dominant negative ALK7. Elevated glucose concentrations and fatty acid (palmitate) markedly increased expression levels of ALK7 transcripts and proteins in INS-1 and rat islets and increased beta cell apoptosis. Activation of ALK7 increased Smad2 phosphorylation, reduced protein kinase B (Akt) kinase activity and was associated with increased levels of the bioactive forms of caspase-3, whereas co-expression of constitutively active ALK7 with dominant negative Smad2 or constitutively active Akt significantly diminished ALK7-induced growth inhibition and apoptosis in INS-1 cells. Although overexpression of constitutively active Akt significantly reduced ALK7-induced growth inhibition and ALK7-enhanced beta cell apoptosis, ALK7-stimulated Smad2 phosphorylation was not affected. Conclusions/ interpretation: These results suggest that the pancreatic beta cell apoptosis induced by ALK7 activation occurs via the activation of two distinct downstream pathways: the suppression of Akt activation and the activation of the Smad2-caspase-3 cascade.

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“…Sel T sitotoksik akan menghasilkan perforin, granzim, dan Fas ligand untuk memicu sinyal apoptosis. 9 Malondialdehid merupakan marker stres oksidatif akibat peroksidasi lipid. Malondialdehid berada dalam berbagai bentuk bergantung pada pH.…”

Section: Pendahuluanunclassified

Paparan Debu Batubara Subkronik pada Peroksidasi Lipid dan Kadar Gula Darah Tikus Diabetes Melitus

Yuwono¹,

Setiawan²,

Kania³

et al. 2011

mkb

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AbstrakDi Kalimantan Selatan, prevalensi penderita diabetes melitus sebesar 11,1%. Kalimantan Selatan merupakan provinsi dengan tambang batubara tersebar di seluruh wilayah. Hal ini menjadikan penderita diabetes melitus terpapar debu batubara. Penelitian ini bertujuan untuk mengukur peroksidasi lipid akibat paparan debu batubara subkronik dan pengaruhnya pada kadar gula darah tikus diabetes melitus. Kelompok penelitian meliputi tikus Wistar diabetes melitus (P1), kelompok diabetes melitus + paparan debu batubara dosis 12,5 mg/m 3 1 jam/hari selama 28 hari (P2), dan kelompok diabetes melitus + paparan debu batubara dosis 25 mg/m 3 1 jam/hari selama 28 hari (P3), masing-masing 6 ekor. Penelitian dilakukan mulai Agustus-Oktober 2010. Uji analysis of variance (ANOVA) terhadap kadar malondialdehid (MDA) plasma tidak didapatkan peningkatan secara bermakna antara kelompok perlakuan (p>0,05). Penurunan kadar gula untuk P1, P2, dan P3 berturut-turut sebesar 23,6%, 16,9%, dan 9,3%. Analisis uji t tidak berpasangan terhadap kadar gula darah tidak didapatkan perbedaan bermakna sebelum dan setelah perlakuan pada semua kelompok (p>0,05). Tidak terdapat korelasi antara kadar MDA plasma dan kadar gula darah setelah perlakuan pada berbagai kelompok (p>0,05). Disimpulkan bahwa paparan debu batubara subkronik tidak meningkatkan peroksidasi lipid yang mempengaruhi kadar gula darah pada tikus diabetes melitus dan tidak ada korelasi antara kadar MDA dan glukosa darah. [MKB. 2011;43(4):189-92].Kata kunci: Debu batubara, diabetes melitus, hiperglikemia, peroksidasi lipid Subchronic Coal Dust Exposure on Lipid Peroxidation and Blood Glucose Level in Diabetes Mellitus Rat AbstractIn South Kalimantan, prevalence of diabetes mellitus was 11.1%. South Kalimantan is a province with coal mine spread in all districts. This condition induce coal dust exposure on diabetes mellitus patients. Aim of this study was to measure lipid peroxidation by subchronic coal dust exposure and its effect on glucose level in Wistar rats model of diabetes mellitus. Group included diabetes mellitus Wistar rats (P1), diabetes mellitus + coal dust exposure at dose 12.5 mg/m 3 1 hour/day for 28 days (P2) and diabetes mellitus + coal dust exposure at dose 25 mg/m 3 1 hour/day for 28 days (P3) on 6 rats, respectively. This research was done from August-October 2010. Analysis of variance (ANOVA) test concluded no significant differently on increased plasma malondialdehyde (MDA) level between all groups (p>0.05). Percentage of blood glucose level decreased 23.6%, 16.9% and 9.3% for P1, P2, P3 group, respectively. Unpaired t test concluded that blood glucose level were not significant differently between pre and post treatment in all groups (p>0.05). There was no correlation between plasma MDA level and blood glucose level in all groups of exposure (p>0.05). In conclusions, that subchronic coal dust exposure doesn't increase lipid peroxidation and no effect on blood glucose level in diabetes mellitus rats and no correlation between MDA dan blood glucose level. [MKB. 2011;...

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Role of caspases in the regulation of apoptotic pancreatic islet beta‐cells death

Cited by 95 publications

References 250 publications

Glucose-dependent Insulinotropic Polypeptide (GIP) Stimulation of Pancreatic β-Cell Survival Is Dependent upon Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (PKB) Signaling, Inactivation of the Forkhead Transcription Factor Foxo1, and Down-regulation of bax Expression

Glucose-dependent Insulinotropic Polypeptide (GIP) Stimulation of Pancreatic β-Cell Survival Is Dependent upon Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (PKB) Signaling, Inactivation of the Forkhead Transcription Factor Foxo1, and Down-regulation of bax Expression

Activin receptor-like kinase 7 induces apoptosis of pancreatic beta cells and beta cell lines

Paparan Debu Batubara Subkronik pada Peroksidasi Lipid dan Kadar Gula Darah Tikus Diabetes Melitus

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