scholarly journals Unbiased Profiling of the Human Proinsulin Biosynthetic Interaction Network Reveals a Role for Peroxiredoxin 4 in Proinsulin Folding

Diabetes ◽  
2020 ◽  
Vol 69 (8) ◽  
pp. 1723-1734
Author(s):  
Duc T. Tran ◽  
Anita Pottekat ◽  
Saiful A. Mir ◽  
Salvatore Loguercio ◽  
Insook Jang ◽  
...  
Keyword(s):  
Interaction Network ◽  
Human Proinsulin

scholarly journals Unbiased profiling of the human proinsulin biosynthetic interaction network reveals a role for peroxiredoxin 4 in proinsulin folding

2020 ◽  
Author(s):  
Ada Admin ◽  
Duc T. Tran ◽  
Anita Pottekat ◽  
Saiful A. Mir ◽  
Salvatore Loguercio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Beta Cell ◽  
Secretory Pathway ◽  
Cell Function ◽  
Affinity Purification ◽  
Interaction Network ◽  
Human Islets ◽  
Cell Protein ◽  
Insulin Biosynthesis ◽  
Human Proinsulin

The beta cell protein synthetic machinery is dedicated to the production of mature insulin, which requires the proper folding and trafficking of its precursor, proinsulin. The complete network of proteins that mediate proinsulin folding and advancement through the secretory pathway, however, remains poorly defined. Here we used affinity purification and mass spectrometry to identify for the first time, the proinsulin biosynthetic interaction network in human islets. Stringent analysis established a central node of proinsulin interactions with ER folding factors, including chaperones and oxidoreductases, that is remarkably conserved in both sexes and across three ethnicities. The ER-localized peroxiredoxin PRDX4 was identified as a prominent proinsulin interacting protein. In beta cells, gene silencing of PRDX4 rendered proinsulin susceptible to misfolding, particularly in response to oxidative stress, while exogenous PRDX4 improved proinsulin folding. Moreover, proinsulin misfolding induced by oxidative stress or high glucose was accompanied by sulfonylation of PRDX4, a modification known to inactivate peroxiredoxins. Notably, islets from patients with Type II diabetes (T2D) exhibited significantly higher levels of sulfonylated PRDX4 than islets from healthy individuals. In conclusion, we have generated the first reference map of the human proinsulin interactome to identify critical factors controlling insulin biosynthesis, beta cell function, and T2D.

scholarly journals Unbiased profiling of the human proinsulin biosynthetic interaction network reveals a role for peroxiredoxin 4 in proinsulin folding

2020 ◽  
Author(s):  
Ada Admin ◽  
Duc T. Tran ◽  
Anita Pottekat ◽  
Saiful A. Mir ◽  
Salvatore Loguercio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Beta Cell ◽  
Secretory Pathway ◽  
Cell Function ◽  
Affinity Purification ◽  
Interaction Network ◽  
Human Islets ◽  
Cell Protein ◽  
Insulin Biosynthesis ◽  
Human Proinsulin

The beta cell protein synthetic machinery is dedicated to the production of mature insulin, which requires the proper folding and trafficking of its precursor, proinsulin. The complete network of proteins that mediate proinsulin folding and advancement through the secretory pathway, however, remains poorly defined. Here we used affinity purification and mass spectrometry to identify for the first time, the proinsulin biosynthetic interaction network in human islets. Stringent analysis established a central node of proinsulin interactions with ER folding factors, including chaperones and oxidoreductases, that is remarkably conserved in both sexes and across three ethnicities. The ER-localized peroxiredoxin PRDX4 was identified as a prominent proinsulin interacting protein. In beta cells, gene silencing of PRDX4 rendered proinsulin susceptible to misfolding, particularly in response to oxidative stress, while exogenous PRDX4 improved proinsulin folding. Moreover, proinsulin misfolding induced by oxidative stress or high glucose was accompanied by sulfonylation of PRDX4, a modification known to inactivate peroxiredoxins. Notably, islets from patients with Type II diabetes (T2D) exhibited significantly higher levels of sulfonylated PRDX4 than islets from healthy individuals. In conclusion, we have generated the first reference map of the human proinsulin interactome to identify critical factors controlling insulin biosynthesis, beta cell function, and T2D.

47-OR: A Reference Map of the Human Proinsulin Biosynthetic Interaction Network

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 47-OR
Author(s):  
DUC T. TRAN ◽  
PETER ARVAN ◽  
RANDAL J. KAUFMAN ◽  
PAMELA ITKIN-ANSARI
Keyword(s):  
Interaction Network ◽  
Human Proinsulin ◽  
Reference Map

Immunologic aspects of human proinsulin therapy

Diabetes ◽  
1988 ◽  
Vol 37 (3) ◽  
pp. 276-280 ◽  
Author(s):  
S. E. Fineberg ◽  
M. J. Rathbun ◽  
S. Hufferd ◽  
N. S. Fineberg ◽  
C. T. Spradlin ◽  
...  
Keyword(s):  
Human Proinsulin

A radioimmunoassay for circulating human proinsulin

Diabetes ◽  
1985 ◽  
Vol 34 (1) ◽  
pp. 84-91 ◽  
Author(s):  
R. M. Cohen ◽  
T. Nakabayashi ◽  
P. M. Blix ◽  
P. A. Rue ◽  
S. E. Shoelson ◽  
...  
Keyword(s):  
Human Proinsulin

Proinsulin conversion in GH3 cells after coexpression of human proinsulin with the endoproteases PC2 and/or PC3

Diabetes ◽  
1997 ◽  
Vol 46 (6) ◽  
pp. 978-982 ◽  
Author(s):  
J. E. Kaufmann ◽  
J. C. Irminger ◽  
J. Mungall ◽  
P. A. Halban
Keyword(s):  
Gh3 Cells ◽  
Human Proinsulin

Imaging the “social brain” in schizophrenia: A systematic review of neuroimaging studies of social reward and punishment

2020 ◽  
Author(s):  
Jessica Mow ◽  
Arti Gandhi ◽  
Daniel Fulford
Keyword(s):  
Brain Activity ◽  
Interaction Network ◽  
Social Motivation ◽  
Social Impairment ◽  
Future Research ◽  
Social Reward ◽  
Schizophrenia Spectrum Disorders ◽  
Social Stimuli ◽  
Schizophrenia Spectrum ◽  
Reward And Punishment

Decreased social functioning and high levels of loneliness and social isolation are common in schizophrenia spectrum disorders (SSD), contributing to reduced quality of life. One key contributor to social impairment is low social motivation, which may stem from aberrant neural processing of socially rewarding or punishing stimuli. To summarize research on the neurobiology of social motivation in SSD, we performed a systematic literature review of neuroimaging studies involving the presentation of social stimuli intended to elicit feelings of reward and/or punishment. Across 11 studies meeting criteria, people with SSD demonstrated weaker modulation of brain activity in regions within a proposed social interaction network, including prefrontal, cingulate, and striatal regions, as well as the amygdala and insula. Firm conclusions regarding neural differences in SSD in these regions, as well as connections within networks, are limited due to conceptual and methodological inconsistencies across the available studies. We conclude by making recommendations for the study of social reward and punishment processing in SSD in future research.

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