Sci Rep. 2019 Feb 27;9(1):2895. doi: 10.1038/s41598-019-39681-6.
Protein SUMOylation regulates insulin secretion at multiple stages.
Type-II
Diabetes Mellitus (T2DM) is one of the fastest growing public health
issues of modern times, consuming 12% of worldwide health budgets and
affecting an estimated 400 million people. A key pathological trait
associated with this disease is the failure of normal glucose-stimulated
insulin secretion (GSIS) from pancreatic beta cells. Several lines of
evidence suggest that vesicle trafficking events such as insulin
secretion are regulated by the post-translational modification,
SUMOylation, and indeed SUMOylation has been proposed to act as a
'brake' on insulin exocytosis. Here, we show that diabetic stimuli which
inhibit GSIS are correlated with an increase in cellular protein
SUMOylation, and that inhibition of deSUMOylation
reduces GSIS.
We demonstrate that manipulation of cellular protein SUMOylation levels, by overexpression of several different components of the SUMOylation pathway, have varied and complex effects on GSIS, indicating that SUMOylation regulates this process at multiple stages. We further demonstrate that inhibition of syntaxin1A SUMOylation, via a knockdown-rescue strategy, greatly enhances GSIS. Our data are therefore consistent with the model that SUMOylation acts as a brake on GSIS, and we have identified SUMOylation of syntaxin 1 A as a potential component of this brake. However, our data also demonstrate that the role of SUMOylation in GSIS is complex and may involve many substrates.
We demonstrate that manipulation of cellular protein SUMOylation levels, by overexpression of several different components of the SUMOylation pathway, have varied and complex effects on GSIS, indicating that SUMOylation regulates this process at multiple stages. We further demonstrate that inhibition of syntaxin1A SUMOylation, via a knockdown-rescue strategy, greatly enhances GSIS. Our data are therefore consistent with the model that SUMOylation acts as a brake on GSIS, and we have identified SUMOylation of syntaxin 1 A as a potential component of this brake. However, our data also demonstrate that the role of SUMOylation in GSIS is complex and may involve many substrates.
- PMID:
- 30814610
- PMCID:
- PMC6393506
- DOI:
- 10.1038/s41598-019-39681-6
Inga kommentarer:
Skicka en kommentar