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Adrenergic receptor stimulation suppresses oxidative metabolism in isolated rat islets and Min6 cells.

ABSTRACT: Insulin secretion is stimulated by glucose metabolism and inhibited by catecholamines through adrenergic receptor stimulation. We determined whether catecholamines suppress oxidative metabolism in ?-cells through adrenergic receptors. In Min6 cells and isolated rat islets, epinephrine decreased oxygen consumption rates compared to vehicle control or co-administration of epinephrine with ?2-adrenergic receptor antagonist yohimbine. Epinephrine also decreased forskolin-stimulated oxygen consumption rates, indicating cAMP dependent and independent actions. Furthermore, glucose oxidation rates were decreased with epinephrine, independent of the exocytosis of insulin, which was blocked with yohimbine. We evaluated metabolic targets through proteomic analysis after 4?h epinephrine exposure that revealed 466 differentially expressed proteins that were significantly enriched for processes including oxidative metabolism, protein turnover, exocytosis, and cell proliferation. These results demonstrate that acute ?2-adrenergic stimulation suppresses glucose oxidation in ?-cells independent of nutrient availability and insulin exocytosis, while cAMP concentrations are elevated. Proteomics and immunoblots revealed changes in electron transport chain proteins that were correlated with lower metabolic reducing equivalents, intracellular ATP concentrations, and altered mitochondrial membrane potential implicating a new role for adrenergic control of mitochondrial function and ultimately insulin secretion.

SUBMITTER: Kelly AC

PROVIDER: S-EPMC6045463 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Adrenergic receptor stimulation suppresses oxidative metabolism in isolated rat islets and Min6 cells.

Kelly Amy C AC Camacho Leticia E LE Pendarvis Ken K Davenport Hailey M HM Steffens Nathan R NR Smith Kate E KE Weber Craig S CS Lynch Ronald M RM Papas Klearchos K KK Limesand Sean W SW

Molecular and cellular endocrinology 20180131

Insulin secretion is stimulated by glucose metabolism and inhibited by catecholamines through adrenergic receptor stimulation. We determined whether catecholamines suppress oxidative metabolism in β-cells through adrenergic receptors. In Min6 cells and isolated rat islets, epinephrine decreased oxygen consumption rates compared to vehicle control or co-administration of epinephrine with α2-adrenergic receptor antagonist yohimbine. Epinephrine also decreased forskolin-stimulated oxygen consumptio ...[more]

PMID: 29360563

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Project description:Hemin is an activator of heme oxygenase-1 (HO-1), an enzyme catalyzing heme degradation. Up-regulation of HO-1 is observed in response to various pathological conditions. Moreover, pharmacological activation of HO-1 is associated with numerous beneficial effects in the organism. Hemin was shown to exert, among other, anti-diabetic and anti-obesity properties. These effects are strongly linked with adipose tissue. However, the direct influence of hemin on metabolism of the fat cells have not been explored. The present study aimed to determine the short-term effects of hemin on metabolism of the primary rat adipocytes. We focused on processes directly related to lipid accumulation, such as lipogenesis and lipolysis. For this purpose, the isolated cells were subjected for 2 h to 40 µM hemin, and effects of this compound on insulin-stimulated glucose conversion to lipids, lactate release, lipolysis induced by various stimuli, and also on the antilipolytic action of insulin were determined. It was shown that hemin did not affect insulin-induced lipogenesis and lactate release. However, hemin significantly decreased lipolysis stimulated by epinephrine. The inhibitory effect of hemin on epinephrine-induced lipolysis was not abolished in the presence of SnMP, an inhibitor of HO-1, which suggests hemin action irrespective of this enzyme. Similar inhibitory effects on epinephrine-induced lipolysis were observed in the presence of 3 and 12 mM glucose. Moreover, hemin was shown to reduce epinephrine-induced lipolysis also when glucose was replaced by alanine or by succinate. Apart from changes in epinephrine action, it was found that the lipolytic response of the adipocytes to isoproterenol was also diminished by hemin. However, hemin failed to affect lipolysis stimulated by dibutyryl-cAMP (a direct activator of protein kinase A), forskolin (an activator of adenylate cyclase), and also by DPCPX (an adenosine A1 receptor antagonist). Additionally, epinephrine-induced lipolysis was shown to be decreased by insulin, and this effect was deepened in the presence of hemin. These results indicate that short-term exposure of the adipocytes to hemin does not affect processes related to glucose metabolism, such as lipogenesis and lactate release. However, hemin was found to decrease the lipolytic response to adrenergic stimulation, which is associated with reduced lipid release from adipocytes. Moreover, our results indicate that hemin is also capable of diminishing the exaggerated lipolysis, which occurs in the presence of supraphysiological concentrations of glucose.

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Adrenergic receptor stimulation suppresses oxidative metabolism in isolated rat islets and Min6 cells.

Publications

Adrenergic receptor stimulation suppresses oxidative metabolism in isolated rat islets and Min6 cells.

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