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July 1, 2004Journal of Biological ChemistryOpen Access

Insulin/Foxo1 Pathway Regulates Expression Levels of Adiponectin Receptors and Adiponectin Sensitivity

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Population

Mice models and in vitro hepatocytes and myocytes

Comparison

Insulin modulation vs Respective control conditions

Design

Preclinical

Authors

ATAtsushi TsuchidaTYToshimasa YamauchiYIYusuke Ito

Discussion

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Overview

Insulin downregulates AdipoR1/R2, suggesting a mechanism for adiponectin resistance in hyperinsulinemic obesity; leaves open human relevance and therapeutic targeting.

Key Points

  • Investigate the molecular mechanisms controlling the expression of adiponectin receptors (AdipoR1 and AdipoR2) across physiological and pathophysiological metabolic states.
  • Assessed AdipoR1 and AdipoR2 expression in liver, skeletal muscle, and adipose tissue across fasting/refeeding, streptozotocin-induced insulin deficiency, and ob/ob mouse models.
  • Treated hepatocytes and myocytes with insulin in vitro to map the phosphoinositide 3-kinase/Foxo1 signaling pathway.
  • Quantified adiponectin membrane binding and downstream AMP kinase activation in skeletal muscle tissue from obese mice.
  • AdipoR1/R2 expression in skeletal muscle and liver increased during fasting and was suppressed by refeeding or insulin replenishment, correlating inversely with circulating insulin.
  • Insulin directly decreased AdipoR1/R2 expression in hepatocytes and myocytes in vitro through a PI3K/Foxo1-dependent pathway.
  • Obese (ob/ob) mice showed significantly reduced AdipoR1/R2 expression in muscle and fat, leading to decreased adiponectin binding and impaired AMP kinase activation.

Structured PICO

P
Population
Mice models (fasted/refed, streptozotocin-induced insulin deficiency, ob/ob mice) and in vitro hepatocytes and myocytes
I
Intervention
Insulin modulation (fasting/refeeding, streptozotocin-induced deficiency, insulin replenishment in vivo; insulin incubation in vitro)
C
Comparator
Respective control conditions (e.g., refed state, untreated cells, wild-type mice)
O
Outcome
Expression levels of AdipoR1 and AdipoR2 in insulin target organs (skeletal muscle, liver, adipose tissue)surrogate

Insulin inversely regulates AdipoR1 and AdipoR2 expression via the PI3K/Foxo1 pathway, providing a mechanistic explanation for adiponectin resistance in hyperinsulinemic states such as obesity.

Cite This Study

Tsuchida et al. (2004) studied this question.

synapsesocial.com/papers/6a8a6fbcf030e20138de8a5dhttps://doi.org/10.1074/jbc.m402367200
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