Expression profiling of cell cycle genes in human pancreatic islets with and without type 2 diabetes
Autoimmunity against INS-IGF2 protein expressed in human pancreatic islets.
Sex, Age, Specimen part
View SamplesPancreatic islets are central in type 2-diabetes development, which coincides with increased activity of innate immunity. Intriguingly, human pancreatic islets express many complement genes. The most highly expressed gene was the complement inhibitor CD59 that is GPI anchored to the cell membrane, which unexpectedly was found in high amounts intracellularly in beta cells. Silencing of CD59 strongly suppressed insulin secretion. Importantly, this suppression was unrelated to established CD59 functions, but rather depletion of intracellular CD59. Imaging experiments identified a distal site of inhibition in the exocytotic pathway, but prior to emptying of the insulin granules. Proximity Ligation Assays pin-pointed the mechanism to impaired turnover of exocytosis-regulating SNARE-proteins and CD59 was detected in complex with VAMP2 and syntaxin. CD59 was downregulated by 24-h glucose incubations in human islets, rat cell lines and in islets from three rodent diabetes models.
The complement inhibitor CD59 regulates insulin secretion by modulating exocytotic events.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
TCF7L2 is a master regulator of insulin production and processing.
Sex, Age, Specimen part
View SamplesHere we harnessed the potential of expression arrays in 89 human pancreatic islet donors (different levels of blood glucose (HbA1c)) to identify genes regulated in this relevant tissue for type 2 diabetes (T2D).
TCF7L2 is a master regulator of insulin production and processing.
Sex, Age, Specimen part
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