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The Lipogenic Effect of Insulin Revisited

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Hepatic De Novo Lipogenesis and Regulation of Metabolism

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Abstract

Insulin promotes lipogenesis and suppresses hepatic gluconeogenesis. Paradoxically, the positive effect of insulin on lipid production in liver is maintained under conditions of insulin resistance, unlike its defective action on gluconeogenesis. In this chapter, we revisit this gluconeogenesis-selectivity notion by reviewing evidence that in fact, under normo-insulinemic conditions, insulin acutely reduces de novo lipogenesis in liver. This is mediated by the ability of insulin pulses in portal vein to phosphorylate the Carcino-Embryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1), an abundant protein in liver that promotes hepatic insulin clearance in a phosphorylation-dependent manner. In the presence of sustained hyperinsulinemia, pulsatility of insulin release diminishes together with its signaling, giving way to its chronic positive effect on lipogenic genes transcription. This would set the stage to redefine hepatic insulin resistance as a comprehensive process that includes defective insulin action in glucose as well as lipid production.

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Acknowledgements

The author thanks all the past and current trainees, and collaborators who participated in the studies of the effect of CEACAM1. This work was supported by grants from the NIH R01 DK054254, R01 DK083850, R01 HL112248 and 5P01 HL036573 to SMN.

Disclosures: None.

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Authors and Affiliations

  1. Center for Diabetes and Endocrine Research, University of Toledo College of Medicine and Life Sciences, Health Science Campus, 3000 Arlington Ave., Mail Stop 1009, Block Health Science Bldg., CeDER, Toledo, OH, 43614-2598, USA

    Sonia M. Najjar Ph.D.

  2. Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Sonia M. Najjar Ph.D.

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  1. Sonia M. Najjar Ph.D.
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Correspondence to Sonia M. Najjar Ph.D. .

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  1. Departments of Biochemistry and Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA

    James M. Ntambi

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Najjar, S.M. (2016). The Lipogenic Effect of Insulin Revisited. In: Ntambi, J. (eds) Hepatic De Novo Lipogenesis and Regulation of Metabolism. Springer, Cham. https://doi.org/10.1007/978-3-319-25065-6_14

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