Le lysosome a cinquante ans

Duve, Christian de

doi:10.1051/medsci/20052111s12

Cited by 2 publications

(1 citation statement)

References 18 publications

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“…Previously, de Duve had discovered the presence of lysosomes in mammalian cells, organelles with an acidic matrix containing a large number of hydrolases responsible for intracellular degradation of proteins and other macromolecules [26]. However, most of our current knowledge about autophagy has been acquired in the last decade, particularly by intensive genetic, molecular and cellular research carried out in the yeast Saccharomyces cerevisiae .…”

Section: Introductionmentioning

confidence: 99%

Autophagy in Trypanosomatids

Brennand

Rico

Michels

2012

Cells

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Autophagy is a ubiquitous eukaryotic process that also occurs in trypanosomatid parasites, protist organisms belonging to the supergroup Excavata, distinct from the supergroup Opistokontha that includes mammals and fungi. Half of the known yeast and mammalian AuTophaGy (ATG) proteins were detected in trypanosomatids, although with low sequence conservation. Trypanosomatids such as Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are responsible for serious tropical diseases in humans. The parasites are transmitted by insects and, consequently, have a complicated life cycle during which they undergo dramatic morphological and metabolic transformations to adapt to the different environments. Autophagy plays a major role during these transformations. Since inhibition of autophagy affects the transformation, survival and/or virulence of the parasites, the ATGs offer promise for development of drugs against tropical diseases. Furthermore, various trypanocidal drugs have been shown to trigger autophagy-like processes in the parasites. It is inferred that autophagy is used by the parasites in an—not always successful—attempt to cope with the stress caused by the toxic compounds.

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Section: Introductionmentioning

confidence: 99%

Autophagy in Trypanosomatids

Brennand

Rico

Michels

2012

Cells

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Loss of insulin-induced inhibition of glucagon gene transcription in hamster pancreatic islet alpha cells by long-term insulin exposure

et al. 2008

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Aims/hypothesis Diabetes mellitus type 2 is characterised by hyperglucagonaemia, resulting in hepatic glucose production and hyperglycaemia. Considering that insulin inhibits glucagon secretion and gene transcription, hyperglucagonaemia in the face of hyperinsulinaemia in diabetes mellitus type 2 suggests that there is insulin resistance also at the glucagon-producing pancreatic islet alpha cells. However, the molecular mechanism of alpha cell insulin resistance is unknown. Therefore, the effect of molecules implicated in conferring insulin resistance in some other tissues was investigated on insulin-induced inhibition of glucagon gene transcription in alpha cells. Methods Reporter gene assays and biochemical techniques were used in the glucagon-producing hamster pancreatic islet alpha cell line InR1-G9.Results From among 16 agents tested, chronic insulin treatment was found to abolish insulin-induced inhibition of glucagon gene transcription. Overproduction of constitutively active protein kinase B (PKB) still inhibited glucagon gene transcription after chronic insulin treatment; together with a markedly reduced insulin-induced phosphorylation and, thus, activation of PKB, this indicates that targets upstream of PKB within the insulin signalling pathway are affected. Indeed, chronic insulin treatment markedly reduced IRS-1 phosphorylation, insulin receptor (IR) autophosphorylation and IR content. Cycloheximide and in vivo labelling experiments attributed IR downregulation to enhanced degradation. Conclusions/interpretation These results show that an extended exposure of alpha cells to insulin induces IR downregulation and loss of insulin-induced inhibition of glucagon gene transcription. They suggest that hyperinsulinaemia, through IR downregulation, may confer insulin resistance to pancreatic islet alpha cells in diabetes mellitus type 2.

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Le lysosome a cinquante ans

Cited by 2 publications

References 18 publications

Autophagy in Trypanosomatids

Autophagy in Trypanosomatids

Loss of insulin-induced inhibition of glucagon gene transcription in hamster pancreatic islet alpha cells by long-term insulin exposure

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