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Ghrelin secretion stimulated by {beta}1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice.

ABSTRACT: Ghrelin, an octanoylated peptide hormone produced in the stomach, rises dramatically in mouse plasma during chronic severe calorie deprivation, an event that is essential to maintain life. The mechanism for this increase is not understood. Here, we study the control of ghrelin secretion in tissue culture cells derived from mice bearing ghrelinomas induced by a tissue-specific SV40 T-antigen transgene. We found that the ghrelin-secreting cells express high levels of mRNA encoding beta(1)-adrenergic receptors. Addition of norepinephrine or epinephrine to the culture medium stimulated ghrelin secretion, and this effect was blocked by atenolol, a selective beta(1)-adrenergic antagonist. When WT mice were treated with reserpine to deplete adrenergic neurotransmitters from sympathetic neurons, the fasting-induced increase in plasma ghrelin was blocked. Inhibition was also seen following atenolol administration. We conclude that ghrelin secretion during fasting is induced by adrenergic agents released by sympathetic neurons and acting directly on beta(1) receptors on the ghrelin-secreting cells of the stomach.

SUBMITTER: Zhao TJ

PROVIDER: S-EPMC2936616 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Ghrelin secretion stimulated by {beta}1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice.

Zhao Tong-Jin TJ Sakata Ichiro I Li Robert Lin RL Liang Guosheng G Richardson James A JA Brown Michael S MS Goldstein Joseph L JL Zigman Jeffrey M JM

Proceedings of the National Academy of Sciences of the United States of America 20100816 36

Ghrelin, an octanoylated peptide hormone produced in the stomach, rises dramatically in mouse plasma during chronic severe calorie deprivation, an event that is essential to maintain life. The mechanism for this increase is not understood. Here, we study the control of ghrelin secretion in tissue culture cells derived from mice bearing ghrelinomas induced by a tissue-specific SV40 T-antigen transgene. We found that the ghrelin-secreting cells express high levels of mRNA encoding beta(1)-adrenerg ...[more]

PMID: 20713709

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Project description:Abstract The anabolic response of aged bone to skeletal loading is typically poor. Efforts to improve mechanotransduction in aged bone have met with limited success. This study investigated whether the bone response to direct skeletal loading is improved by reducing sympathetic suppression of osteoblastic bone formation via β2AR. To test this possibility, we treated aged wild‐type C57BL/6 mice with a selective β2AR antagonist, butaxamine (Butax), before each of nine bouts of cantilever bending of the right tibia. Midshaft periosteal bone formation was assessed by dynamic histomorphometry of loaded and contralateral tibias. Butax treatment did not alter osteoblast activity of contralateral tibias. Loading alone induced a modest but significant osteogenic response. However, when loading was combined with Butax pretreatment, the anabolic response was significantly elevated compared with loading preceded by saline injection. Subsequent studies in osteoblastic cultures revealed complex negative interactions between adrenergic and mechanically induced intracellular signaling. Activation of β2AR by treatment with the β1, β2‐agonist isoproterenol (ISO) before fluid flow exposure diminished mechanically stimulated ERK1/2 phosphorylation in primary bone cell outgrowth cultures and AKT phosphorylation in MC3T3‐E1 pre‐osteoblast cultures. Expression of mechanosensitive Fos and Ptgs2 genes was enhanced with ISO treatment and reduced with flow in both MC3T3‐E1 and primary cultures. Finally, co‐treatment of MC3T3‐E1 cells with Butax reversed these ISO effects, confirming a critical role for β2AR in these responses. In combination, these results demonstrate that selective inhibition of β2AR is sufficient to enhance the anabolic response of the aged skeleton to loading, potentially via direct effects upon osteoblasts. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Project description:ContextGlucagon-like peptide 1 (GLP-1), an insulinotropic peptide released into the circulation from intestinal enteroendocrine cells, is considered a hormonal mediator of insulin secretion. However, the physiological actions of circulating GLP-1 have been questioned because of the short half-life of the active peptide. Moreover, there is mounting evidence for localized, intra-islet mediation of GLP-1 receptor (GLP-1r) signaling including a role for islet dipeptidyl-peptidase 4 (DPP4).ObjectiveTo determine whether GLP-1r signaling contributes to insulin secretion in the absence of enteral stimulation and increased plasma levels, and whether this is affected by DPP4.MethodsSingle-site study conducted at an academic medical center of 20 nondiabetic subjects and 13 subjects with type 2 diabetes. This was a crossover study in which subjects received either a DPP4 inhibitor (DPP4i; sitagliptin) or placebo on 2 separate days. On each day they received a bolus of intravenous (IV) arginine during sequential 60-minute infusions of the GLP-1r blocker exendin[9-39] (Ex-9) and saline. The main outcome measures were arginine-stimulated secretion of C-Peptide (C-PArg) and insulin (InsArg).ResultsPlasma GLP-1 remained at fasting levels throughout the experiments and IV arginine stimulated both α- and β-cell secretion in all subjects. Ex-9 infusion reduced C-PArg in both the diabetic and nondiabetic groups by ~14% (P < .03 for both groups). Sitagliptin lowered baseline glycemia but did not affect the primary measures of insulin secretion. However, a significant interaction between sitagliptin and Ex-9 suggested more GLP-1r activation with DPP4i treatment in subjects with diabetes.ConclusionGLP-1r activation contributes to β-cell secretion in diabetic and nondiabetic people during α-cell activation, but in the absence of increased circulating GLP-1. These results are compatible with regulation of β-cells by paracrine signals from α-cells. This process may be affected by DPP4 inhibition.

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Ghrelin secretion stimulated by {beta}1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice.

Publications

Ghrelin secretion stimulated by {beta}1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice.

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