Journal
CELL METABOLISM
Volume 26, Issue 3, Pages 568-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2017.08.013
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Funding
- NIH [AI42288, UC4 DK108132]
- JDRF
- Leona M. and Harry B. Helmsley Charitable Trust
- Brehm Coalition
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The canonical notion that type 1 diabetes (T1D) results following a complete destruction of beta cells has recently been questioned as small amounts of C-peptide are detectable in patients with long-standing disease. We analyzed protein and gene expression levels for proinsulin, insulin, C-peptide, and islet amyloid polypeptide within pancreatic tissues from T1D, autoantibody positive (Ab+), and control organs. Insulin and C-peptide levels were low to undetectable in extracts from the T1D cohort; however, proinsulin and INS mRNA were detected in the majority of T1D pancreata. Interestingly, heterogeneous nuclear RNA (hnRNA) for insulin and INS-IGF2, both originating from the INS promoter, were essentially undetectable in T1D pancreata, arguing for a silent INS promoter. Expression of PCSK1, a convertase responsible for proinsulin processing, was reduced in T1D pancreata, supportive of persistent proinsulin. These data implicate the existence of beta cells enriched for inefficient insulin/C-peptide production in T1D patients, potentially less susceptible to autoimmune destruction.
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