Role of β-adrenoceptors in glucose uptake in astrocytes using β-adrenoceptor knockout mice.

ABSTRACT:

Background and purpose

β(1) -, β(2) - and β(3) -adrenoceptors determined by functional, binding and reverse transcription polymerase chain reaction (RT-PCR) studies are present in chick astrocytes and activation of β(2) - or β(3) -adrenoceptors increase glucose uptake. The aims of the present study are to identify which β-adrenoceptor subtypes are present in mouse astrocytes, the signal transduction mechanisms involved and whether β-adrenoceptor stimulation regulates glucose uptake.

Experimental approach

Astrocytes were prepared from four mouse strains: FVB/N, DBA/1 crossed with C57BL/6J, β(3) -adrenoceptor knockout and β(1) β(2) -adrenoceptor knockout mice. RT-PCR and radioligand binding studies were used to determine β-adrenoceptor expression. Glucose uptake and cAMP were assayed to elucidate the signalling pathways involved.

Key results

mRNAs for all three β-adrenoceptors were identified in astrocytes from wild-type mice. Radioligand binding studies identified that β(1) - and β(3) -adrenoceptors were predominant. cAMP studies showed that β(1) - and β(2) -adrenoceptors coupled to G(s) whereas β(3) -adrenoceptors coupled to both G(s) and G(i) . However, activation of any of the three β-adrenoceptors increased glucose uptake in mouse astrocytes. Interestingly, there was no functional compensation for receptor subtype loss in knockout animals.

Conclusions and implications

This study demonstrates that although β(1) -adrenoceptors are the predominant β-adrenoceptor in mouse astrocytes and are primarily responsible for cAMP production in response to β-adrenoceptor stimulation, β(3) -adrenoceptors are also present in mouse astrocytes and activation of β(2) - and β(3) -adrenoceptors increases glucose uptake in mouse astrocytes.

SUBMITTER: Catus SL 

PROVIDER: S-EPMC3081115 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature