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Based on my review of the GO-CAM model (gomodel:62f58d8800003012) "Positive regulation of insulin secretion 2 (Mouse)" and the supporting documentation, I'll now provide a comprehensive review:

GO-CAM Model Review - gomodel:62f58d8800003012

Overview

This GO-CAM model represents the positive regulation of insulin secretion pathway in mouse pancreatic beta cells, specifically focusing on the GPR40 (FFAR1)-mediated pathway that involves store-operated calcium entry (SOCE) through the IP3R1/STIM1/Orai1 pathway. The model depicts how long-chain fatty acids potentiate glucose-induced insulin secretion.

Strengths of the Model

  1. Biological Accuracy: The model accurately represents the current understanding of GPR40/FFAR1 signaling in pancreatic beta cells as documented in the literature (PMID:31664108). The pathway from G-protein coupled receptor activation through to calcium channel regulation is well-represented.

  2. Proper Evidence Annotation: Most activities and relationships are supported by appropriate experimental evidence codes and literature references.

  3. Molecular Detail: The model includes appropriate molecular details, including relevant inputs (such as IP3 and DAG) and causal relationships between activities.

  4. Biological Process Context: All activities are properly situated within the broader biological process (GO:0007200 - phospholipase C-activating G protein-coupled receptor signaling pathway).

Areas for Improvement

  1. Missing Causal Association Evidence: There's a causal association between Orai1 (MGI:MGI:1925542) activity and TRPC1 (MGI:MGI:109528) activity that lacks evidence annotation. This should be supported with appropriate evidence.

  2. Cellular Location Annotations: While most activities have appropriate cellular location annotations (plasma membrane, GO:0005886), some activities lack these annotations. For example, IP3R1 activity would typically occur at the endoplasmic reticulum membrane, but this location is not specified.

  3. Biological Process Consistency: While all activities are annotated to GO:0007200 (phospholipase C-activating G protein-coupled receptor signaling pathway), the title of the model is "Positive regulation of insulin secretion 2 (Mouse)". It would be beneficial to explicitly link this to insulin secretion in the model (GO:0030073) to better match the stated purpose.

  4. Complete Input/Output Relationships: While some reactions in the model have appropriate input/output molecule associations (e.g., PLC activity with PIP2 input and IP3/DAG outputs), others are missing potential input/output annotations that would enhance the model's clarity.

  5. Incomplete Pathway: The model shows the pathway up to TRPC1 activity but does not complete the connection to insulin secretion, which would provide a more comprehensive representation of the title process.

Technical Issues

  1. Evidence Codes: The model appropriately uses evidence codes like ECO:0000315 (mutant phenotype evidence used in manual assertion) and ECO:0000266 (sequence orthology evidence used in manual assertion) to support the assertions, which is good practice.

  2. Regulatory Relationships: The model correctly uses RO:0002629 (directly positively regulates) to represent the causal relationships between activities in the pathway.

Biological Recommendations

  1. Complete the Pathway: Consider extending the model to show how the SOCE pathway ultimately leads to insulin secretion, which would complete the story suggested by the model title.

  2. Include Glucose Dependency: The literature (PMID:31664108) emphasizes that GPR40-mediated potentiation of insulin secretion is glucose-dependent. This aspect could be better represented in the model.

  3. Add Cellular Compartmentalization: The model would benefit from more precise cellular location annotations, particularly for IP3R1, which functions at the endoplasmic reticulum membrane.

Conclusion

This GO-CAM model (https://bioregistry.io/go.model:62f58d8800003012) provides a good representation of the GPR40/FFAR1 signaling pathway that leads to store-operated calcium entry in pancreatic beta cells. The model follows most GO-CAM best practices and is supported by appropriate evidence. With some minor improvements, particularly regarding evidence for all causal associations and completing the pathway to insulin secretion, this would be an excellent model for disseminating knowledge about this important signaling pathway in insulin secretion.