Adrenergic Receptor Stimulation Suppresses Metabolism in the Pancreatic β Cell

ABSTRACT: Glucose-stimulated insulin secretion (GSIS) is suppressed through α-adrenergic receptor stimulation by catecholamines, epinephrine and norepinephrine, in pancreatic β-cells. Previous work has elucidated a bevy of adrenergic regulatory mechanisms beyond traditional Gi-coupled signaling including regulation of ion channels and interactions with exocytotic machinery. Glucose oxidation may also be an important site for adrenergic regulation of GSIS, but the link between epinephrine and glucose oxidation in β-cells is undefined. Here, we evaluate whether adrenergic stimulation decreases oxidative metabolism in β cells. Oxygen consumption rates were determined for Min6 and isolated rat islets in 20mM glucose complete media, then epinephrine was added at either 0 nM (vehicle control) or 100nM, followed by 10uM yohimbine (a selective Adrα2A antagonist). To identify glucose oxidation as the primary metabolic pathway affected by epinephrine, oxidation of 14C(U)-labeled glucose was determined in Min6 cells with epinephrine or vehicle. Oxygen consumption and glucose oxidation experiments were conducted in the presence of cAMP and insulin secretion blockers, respectively. Proteomics was performed on Min6 cells exposed to epinephrine for 4 hours and compared to controls. Epinephrine, but not vehicle, reduced (P<0.01) oxygen consumption rates in rat islets and Min6 cells to 64 ± 6% and 65 ± 1% of baseline, respectively, and yohimbine restored oxygen consumption to rates not different from baseline. In Min6 cells incubated with epinephrine rates of 14C glucose oxidation were reduced (P<0.01) 66 ± 4% compared to vehicle controls. These results demonstrate that acute epinephrine exposure suppresses glucose oxidation in β cells via the specific adrenergic receptor, Adrα2A, and indicate a new role for adrenergic regulation in GSIS.

INSTRUMENT(S): Velos Plus

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): B Cell, Pancreas

SUBMITTER: Ken Pendarvis  

LAB HEAD: Sean Limesand

PROVIDER: PXD006330 | Pride | 2019-11-08

REPOSITORIES: Pride