| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-103 |
Sentence |
denotes |
A Novel GLP1 Receptor Interacting Protein ATP6ap2 Regulates Insulin Secretion in Pancreatic Beta Cells. |
| T2 |
104-169 |
Sentence |
denotes |
GLP1 activates its receptor, GLP1R, to enhance insulin secretion. |
| T3 |
170-313 |
Sentence |
denotes |
The activation and transduction of GLP1R requires complex interactions with a host of accessory proteins, most of which remain largely unknown. |
| T4 |
314-459 |
Sentence |
denotes |
In this study, we used membrane-based split ubiquitin yeast two-hybrid assays to identify novel GLP1R interactors in both mouse and human islets. |
| T5 |
460-591 |
Sentence |
denotes |
Among these, ATP6ap2 (ATPase H(+)-transporting lysosomal accessory protein 2) was identified in both mouse and human islet screens. |
| T6 |
592-671 |
Sentence |
denotes |
ATP6ap2 was shown to be abundant in islets including both alpha and beta cells. |
| T7 |
672-817 |
Sentence |
denotes |
When GLP1R and ATP6ap2 were co-expressed in beta cells, GLP1R was shown to directly interact with ATP6ap2, as assessed by co-immunoprecipitation. |
| T8 |
818-988 |
Sentence |
denotes |
In INS-1 cells, overexpression of ATP6ap2 did not affect insulin secretion; however, siRNA knockdown decreased both glucose-stimulated and GLP1-induced insulin secretion. |
| T9 |
989-1098 |
Sentence |
denotes |
Decreases in GLP1-induced insulin secretion were accompanied by attenuated GLP1 stimulated cAMP accumulation. |
| T10 |
1099-1241 |
Sentence |
denotes |
Because ATP6ap2 is a subunit required for V-ATPase assembly of insulin granules, it has been reported to be involved in granule acidification. |
| T11 |
1242-1390 |
Sentence |
denotes |
In accordance with this, we observed impaired insulin granule acidification upon ATP6ap2 knockdown but paradoxically increased proinsulin secretion. |
| T12 |
1391-1554 |
Sentence |
denotes |
Importantly, as a GLP1R interactor, ATP6ap2 was required for GLP1-induced Ca(2+) influx, in part explaining decreased insulin secretion in ATP6ap2 knockdown cells. |
| T13 |
1555-1642 |
Sentence |
denotes |
Taken together, our findings identify a group of proteins that interact with the GLP1R. |
| T14 |
1643-1811 |
Sentence |
denotes |
We further show that one interactor, ATP6ap2, plays a novel dual role in beta cells, modulating both GLP1R signaling and insulin processing to affect insulin secretion. |
