Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Role of the G-Protein Coupled Receptor 3-Salt Inducible Kinase 2 Pathway in Human β CellProliferation Loss of pancreatic {beta} cells is the hallmark of type 1 diabetes (T1D) 1, for which provision of insulin is the standard of care. While regenerative and stem cell therapies hold the promise of generating single-source or host-matched tissue to obviate immune-mediated complications2-4, these will still require surgical intervention and immunosuppression. Thus, methods that harness the innate capacity of {beta}-cells to proliferate to increase {beta} cell mass in vivo are considered vital for future T1D treatment5, 6. However, early in life {beta} cells enter what appears to be a permanent state of quiescence 7-10, directed by an evolutionarily selected genetic program that establishes a {beta} cell mass setpoint to guard against development of fatal endocrine tumours. Here we report the development of a high-throughput RNAi screening approach to identify upstream pathways that regulate adult human {beta} cell quiescence and demonstrate in a screen of the GPCRome that silencing G-protein coupled receptor 3 (GPR3) leads to human pancreatic {beta} cell proliferation. Loss of GPR3 leads to activation of Salt Inducible Kinase 2 (SIK2), which is necessary and sufficient to drive cell cycle entry, increase {beta} cell mass, and enhance insulin secretion in mice. Taken together, targeting the GPR3-SIK2 pathway represents a novel avenue to stimulate the regeneration of {beta} cells.
19
The categories of this paper are: epidemiology
0
The categories of this paper are: genetics
7
The categories of this paper are: ecology
3
The categories of this paper are: evolutionary
1
The categories of this paper are: bioinformatics
18
The categories of this paper are: systems
20
The categories of this paper are: pharmacology
23
The categories of this paper are: immunology
30
The categories of this paper are: scientific
25
The categories of this paper are: bioengineering
16
The categories of this paper are: microbiology
13
The categories of this paper are: animal
29
The categories of this paper are: education
11
The categories of this paper are: cognition
4
The categories of this paper are: neuroscience
12
The categories of this paper are: behavior