2120-P: The Protein Phosphatase M1K Connects Glucose Sensing to Protein Translation in Pancreatic Beta Cells

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2120-P
Author(s):  
YANN DELEYE ◽  
JACOB HERRING ◽  
KAVAN H. HESS ◽  
BRENNAN LEININGER ◽  
ROBERT W. MCGARRAH ◽  
...  
Keyword(s):  
Beta Cells ◽  
Protein Phosphatase ◽  
Pancreatic Beta Cells ◽  
Protein Translation ◽  
Glucose Sensing

scholarly journals Species-Related Differences in the Proteome of Rat and Human Pancreatic Beta Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
G. A. Martens
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Redox Regulation ◽  
Radical Scavenging ◽  
Cell Subset ◽  
Glucose Sensing ◽  
Human Cells ◽  
Label Free ◽  
Human Beta Cells ◽  
Shock Proteins

The core proteomes of human and rat pancreatic beta cells were compared by label-free LC-MS/MS: this resulted in quantification of relative molar abundances of 707 proteins belonging to functional pathways of intermediary metabolism, protein synthesis, and cytoskeleton. Relative molar abundances were conserved both within and between pathways enabling the selection of a housekeeping network for geometric normalization and the analysis of potentially relevant differential expressions. Human beta cells differed from rat beta cells in their lower level of enzymes involved in glucose sensing (MDH1, PC, and ACLY) and upregulation of lysosomal enzymes. Human cells also expressed more heat shock proteins and radical scavenging systems: apart from SOD2, they expressed high levels of H2O2-scavenger peroxiredoxin 3 (PRDX3), confirmed by microarray, Western blotting, and microscopy. Besides conferring lower susceptibility to oxidative stress to human cells PRDX3 might also play a role in physiological redox regulation as, in rat, its expression was restricted to a beta cell subset with higher metabolic glucose responsiveness. In conclusion, although their core proteomic architecture is conserved, human and rat beta cells differ in their molar expression of key enzymes involved in glucose sensing and redox control.

scholarly journals Deletion of ARNT/HIF1β in pancreatic beta cells does not impair glucose homeostasis in mice, but is associated with defective glucose sensing ex vivo

Diabetologia ◽  
2015 ◽  
Vol 58 (12) ◽  
pp. 2832-2842 ◽  
Author(s):  
Renjitha Pillai ◽  
Sabina Paglialunga ◽  
Monica Hoang ◽  
Katelyn Cousteils ◽  
Kacey J. Prentice ◽  
...  
Keyword(s):  
Beta Cells ◽  
Glucose Homeostasis ◽  
Pancreatic Beta Cells ◽  
Ex Vivo ◽  
Glucose Sensing

scholarly journals Tankyrase interacts with the allosteric site of glucokinase and inhibits its glucose-sensing function in the beta cell

2021 ◽  
Author(s):  
Nai-Wen Chi ◽  
Travis Eisemann ◽  
Tsung-Yin J Yeh ◽  
Swati Roy ◽  
Tyler J Chi ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glucose Sensor ◽  
Pancreatic Beta Cell ◽  
Glucose Sensing ◽  
Binding Motif ◽  
Allosteric Site

Insulin secretion in the pancreatic beta cell is rate-limited by glucokinase (GCK), the glucose sensor that catalyzes the first step of glucose metabolism. GCK consists of two lobes connected by a flexible hinge that allows the kinase to sample a spectrum of conformations ranging from the active, closed form to several inactive, less-compact forms. Activating GCK mutations can cause hyperinsulinemia and hypoglycemia in infants. A similar phenotype is exhibited in mice deficient in tankyrase (TNKS), prompting us to investigate whether TNKS might modulate the glucose-sensing function of GCK. We found that TNKS colocalizes and directly interacts with GCK. Their interaction is mediated by two ankyrin-repeat clusters (ARC-2 and -5) in TNKS and a tankyrase-binding motif (TBM, aa 63-68) in the GCK hinge. This interaction is conformation sensitive: human GCK variants that cause hyperglycemia (V62M) or hypoglycemia (S64Y) enhance or diminish the interaction respectively, even though they have no impact on TNKS interaction in the context of a GCK peptide (V62M) or a peptide library (S64Y). Moreover, the TNKS-GCK interaction is inhibited by high concentrations of glucose, which are known to stabilize GCK in the active (closed, glucose-avid) conformation. Conversely, glucose phosphorylation by GCK in vitro is inhibited by TNKS. To validate this in vitro inhibitory effect in the MIN6 beta cells, we showed that glucose-stimulated insulin secretion is suppressed upon stabilization of the TNKS protein and conversely is enhanced upon TNKS knockdown. Based on these findings as well as by contrasting with hexokinase-2, we propose that TNKS is a physiological GCK inhibitor in pancreatic beta cells that acts by trapping the kinase in an open (inactive) conformation.

The loss of Sirt1 in mouse pancreatic beta cells impairs insulin secretion by disrupting glucose sensing

Diabetologia ◽  
2013 ◽  
Vol 56 (9) ◽  
pp. 2010-2020 ◽  
Author(s):  
L. Luu ◽  
F. F. Dai ◽  
K. J. Prentice ◽  
X. Huang ◽  
A. B. Hardy ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glucose Sensing

Osteoprotegerin (OPG) protects pancreatic beta cells from Interleukin-1 induced cell death

2006 ◽  
Vol 114 (S 1) ◽  
Author(s):  
J Schrader ◽  
U Niebergall ◽  
M Schoppet ◽  
D Hörsch ◽  
LC Hofbauer
Keyword(s):  
Cell Death ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Interleukin 1

Glucose-dependent expansion of pancreatic beta-cells by the protein p8 in vitro and in vivo

2007 ◽  
Vol 115 (S 1) ◽  
Author(s):  
G Päth ◽  
A Opel ◽  
M Gehlen ◽  
V Rothhammer ◽  
X Niu ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells

Towards Generating Spatiotemporal Multiscale Models of Human Pancreatic Beta Cells

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2171-P
Author(s):  
KATE L. WHITE ◽  
KYLE MCCLARY ◽  
JITIN SINGLA ◽  
RAYMOND C. STEVENS
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Multiscale Models
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