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 1β 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. © 2011 The British Pharmacological Society.