31. Glucose is mobilized in muscle when epinephrine activates Gas. In an experiment in which muscle cells were stimulated with epinephrine, glucose mobilization was observed even after withdrawal of epinephrine. This could be
(1) due to the presence of a cAMP phosphodiesterase inhibitor
(2) very low rates of cyclic AMP formation.
(3) due to the presence of a cAMP phosphodiesterase activator.
(4) due to the absence of protein kinase A.

Persistent Glucose Mobilization After Epinephrine Withdrawal: Role of cAMP Phosphodiesterase Inhibition

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Introduction

Epinephrine activates muscle glucose mobilization predominantly via the Gs protein-adenylyl cyclase-cAMP pathway. Under normal circumstances, withdrawal of epinephrine leads to cessation of the signal and return to baseline. However, glucose mobilization persisting after epinephrine removal indicates sustained signaling.

Mechanism Behind Persistent Glucose Mobilization

• Epinephrine binding to β-adrenergic receptors activates the Gs protein (Gas), which stimulates adenylyl cyclase to convert ATP into cyclic AMP (cAMP).

• cAMP acts as a second messenger to activate protein kinase A (PKA), which phosphorylates targets leading to glycogen breakdown and glucose release.

• cAMP levels are tightly regulated by phosphodiesterases (PDEs), enzymes that degrade cAMP and terminate signaling.

• Inhibition of PDEs prevents cAMP degradation, sustaining elevated cAMP levels and thereby continued glucose mobilization even after epinephrine withdrawal.

Why Other Options Are Less Plausible

• Very low rates of cAMP formation would decrease signaling, not sustain it.

• Activation of cAMP phosphodiesterase would accelerate cAMP degradation, reducing glucose mobilization.

• Absence of protein kinase A would block downstream signaling, halting glucose mobilization.

Correct Explanation

The observed sustained glucose mobilization is most likely due to:

(1) the presence of a cAMP phosphodiesterase inhibitor

which prevents breakdown of cAMP, thus maintaining PKA activation in the absence of epinephrine.