Powered by OpenAIRE graph

Mutation of the RIIβ Subunit of Protein Kinase A Prevents Diet-Induced Insulin Resistance and Dyslipidemia in Mice

Authors: S A, Schreyer; D E, Cummings; G S, McKnight; R C, LeBoeuf;

Mutation of the RIIβ Subunit of Protein Kinase A Prevents Diet-Induced Insulin Resistance and Dyslipidemia in Mice

Abstract

The mechanisms by which obesity contributes to diabetic phenotypes remain unclear. We evaluated the role of protein kinase A (PKA) signaling events in mediating diabetes associated with obesity. PKA comprises two regulatory subunits and two catalytic subunits and is activated by cAMP. The RIIβ regulatory subunit is abundantly expressed in adipose tissue and brain. Knockout mice lacking this subunit are lean and display remarkable resistance to diet-induced obesity. We investigated whether these mice were also resistant to diet-induced diabetes and whether this effect was dependent on reduced adiposity. Mice were fed a high-fat, high-carbohydrate diet and weight gain and diabetes phenotypes were examined. RIIβ−/− mice displayed decreased body weights, reduced insulin levels, improved insulin sensitivity, and improved total-body glucose disposal as compared with wild-type controls. Plasma levels of VLDL and LDL cholesterol were also reduced in high fat–fed RIIβ−/− mice compared with wild-type mice. Taken together, these data demonstrate that loss of RIIβ protects mice from diet-induced obesity, insulin resistance, and dyslipidemia.

Related Organizations
Keywords

Male, Mice, Knockout, Body Weight, Hyperlipidemias, Cyclic AMP-Dependent Protein Kinases, Lipids, Diet, Mice, Glucose, Phenotype, Adipose Tissue, Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit, Reference Values, Mutation, Diabetes Mellitus, Animals, Insulin, Female, Longitudinal Studies, Insulin Resistance

  • BIP!
    Impact byBIP!
    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    68
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
68
Top 10%
Top 10%
Top 10%