Summary of INSIG2
Insulin-induced gene 2 (INSIG2). INSIG2 gene is associated with obesity [R]. A large genetic association study showed evidence for SNP with obesity in several cohorts [R].
INSIG2 gene was consistently associated with increased BMI [R]. INSIG2 (but not INSIG1) plays a role in fat creation, with a marked increase in gene expression during fat cell creation (R, R2, R3).
The production of INSIG2 also mildly correlates with BMI (R). Therefore, it seems like pro-INSIG2 factors will increase obesity risk.
The Function of INSIG2
Mediates feedback control of cholesterol synthesis by controlling SCAP and HMGCR. Functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs). Capable of retaining the SCAP-SREBF2 complex in the ER thus preventing it from escorting SREBPs to the Golgi. Seems to regulate the ubiquitin-mediated proteasomal degradation of HMGCR.
Protein names
Recommended name:
Insulin-induced gene 2 proteinShort name:
INSIG-2- RS10185316 (INSIG2) ??
- RS10490624 (INSIG2) ??
- RS2161829 (INSIG2) ??
- RS6726538 (INSIG2) ??
- RS7566605 (INSIG2) ??
- RS9308762 (INSIG2) ??
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Top Gene-Substance Interactions
INSIG2 Interacts with These Diseases
| Disease | Score |
Fixes
- Exercise....People with a SNP that causes weight gain with a bad INSIG2 gene lost more weight with exercise (R).
Fixes Advanced
- Insulin increases INSIG2 production (R). Therefore, it's possible a lower carb diet could help curb INSIG2 production and cause weight loss.
- Milk thistle/Silibinin increases INSIG2 (and INSIG1), but it's capable of inhibiting fat cell creation (R).
- Vitamin D/Calcitriol and the VDR (together with RXR) strongly induces INSIG2 (in adipocytes) (R).
- PPARalpha and PPARgamma increased INSIG (which inhibits SREBP-1) (R).
- PGC-1alpha increases INSIG2 (and 1) (R).
- INSIG2 is increased under low oxygen conditions and is associated with pancreatic cancer (R).
Substances That Increase INSIG2
| Substances | Interaction | Organism | Category |
Substances That Decrease INSIG2
| Substances | Interaction | Organism | Category |
Advanced Summary
INSIG-2 blocks lipid synthesis in a cholesterol-dependent fashion (by inhibiting the breakdown of SREBPs) [R]. INSIG2 increases SREBP indirectly.
SREB proteins are required for cholesterol synthesis and for uptake and fatty acid synthesis (INSIG2 binds to SREBP cleavage-activating protein (SCAP), and thus prevent SCAP from escorting SREBPs to the Golgi) (R). On the other hand, INSIG2 reduces the creation of fat cells in early stages (R) and decreases triglycerides (R).
INSIG2 is under circadian control (via REV-ERBalpha) (R). Excess INSIG2 appeared to suppress some of the actions of chemotherapeutic drugs (R).
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Gene Pathways:
Biological Processes:
- Cholesterol Biosynthetic Process
- Cranial Suture Morphogenesis
- Inner Ear Morphogenesis
- Middle Ear Morphogenesis
- Negative Regulation Of Fatty Acid Biosynthetic Process
- Negative Regulation Of Steroid Biosynthetic Process
- Palate Development
- Response To Fatty Acid
- Response To Insulin
- Srebp Signaling Pathway
- Triglyceride Metabolic Process