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Published on: November 16, 2011
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PIMT regulates hepatic gluconeogenesis in mice
Bandish Kapadia1, Soma Behera1, Sireesh T Kumar2
1Center for Innovation in Molecular and Pharmaceutical Sciences, Dr. Reddy's Institute of Life Sciences (DRILS), University of Hyderabad Campus, Hyderabad, TG 500046, India.
Iscience
|March 3, 2023
Summary
The protein PIMT (Phosphatidylinositol methyltransferase) plays a key role in maintaining glucose homeostasis. PKA signaling regulates PIMT, impacting hepatic glucose production and potentially serving as a glucose sensor.
Area of Science:
- Metabolic regulation
- Molecular biology
- Endocrinology
Background:
- The role of Phosphatidylinositol methyltransferase (PIMT/TGS1) in glucose homeostasis is not well understood.
- PIMT/TGS1 is a protein involved in the transcriptional apparatus.
Purpose of the Study:
- To investigate the physiological and metabolic functions of PIMT/TGS1 in glucose homeostasis.
- To elucidate the regulatory mechanisms of PIMT/TGS1 in the liver.
Main Methods:
- Upregulation of PIMT expression in fasted and obese mice models.
- Lentiviral-mediated gene modulation (shRNA and cDNA) of Tgs1 in wild-type mice.
- Assessment of gene expression, hepatic glucose output, glucose tolerance, and insulin sensitivity.
- In vitro studies using primary hepatocytes and cultured cells.
- Analysis of PKA signaling pathway involvement and its effect on PIMT phosphorylation and translation.
Main Results:
- PIMT expression was elevated in the livers of short-term fasted and obese mice.
- Genetic manipulation of PIMT directly enhanced gluconeogenic gene expression and hepatic glucose output.
- Protein Kinase A (PKA) was identified as a regulator of PIMT at post-transcriptional, translational, and post-translational levels.
- PKA promoted TGS1 mRNA translation and PIMT phosphorylation, leading to increased Ep300-mediated gluconeogenic activity.
Conclusions:
- The PKA-PIMT-Ep300 signaling module is a critical driver of hepatic gluconeogenesis.
- PIMT acts as a key hepatic glucose sensor, regulating glucose production.
- Understanding PIMT regulation offers potential therapeutic targets for metabolic disorders.
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