Acute knockdown of the insulin receptor or its substrates Irs1 and 2 in 3T3-L1 adipocytes suppresses adiponectin production

Scientific Reports
M P GroeneveldR K Semple

Abstract

Loss of function of the insulin receptor (INSR) in humans produces severe insulin resistance. Unlike "common" insulin resistance, this is associated with elevated plasma levels of the insulin-sensitising, adipose-derived protein adiponectin. The underlying mechanism for this paradox is unclear, and it is at odds with the acute stimulation of adiponectin secretion reported on insulin treatment of cultured adipocytes. Given recent evidence for ligand-independent actions of the INSR, we used a lentiviral system to knock down Insr or its substrates Irs1 and Irs2 conditionally in 3T3-L1 murine preadipocytes/adipocytes to assess whether acute loss of their expression has different consequences to withdrawal of insulin. Efficient knockdown of either Insr or Irs1/2 was achieved by conditional shRNA expression, severely attenuating insulin-stimulated AKT phosphorylation and glucose uptake. Dual knockdown of Irs1 and Irs2 but not Insr in preadipocytes impaired differentiation to adipocytes. Acute knockdown of Insr or both Irs1 and Irs2 in adipocytes increased Adipoq mRNA expression but reduced adiponectin secretion, assessed by immunoassay. Knockdown sustained for 14 days also reduced immunoassay-detected adiponectin secretion, and moreo...Continue Reading

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Citations

Feb 16, 2020·International Journal of Molecular Sciences·Hyung Muk ChoiKyoung Soo Kim
Oct 3, 2018·Archives of Physiology and Biochemistry·Aziz Ur Rehman AzizBo Liu
Jan 2, 2020·Cellular and Molecular Life Sciences : CMLS·Magdalena LoskoJolanta Jura

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Methods Mentioned

BETA
lipidation
Infection
protein assay
electrophoresis
PCR
antisense oligonucleotides

Software Mentioned

GraphPad Prism

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