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Diabetes

多肽/蛋白质生物标志物和糖尿病治疗

脂肪组织中的多肽/蛋白质对葡萄糖动态平衡的影响

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Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis.

All homeotherms use thermogenesis to maintain their core body temperature, ensuring that cellular functions and physiological processes can continue in cold environments. In the prevailing model of thermogenesis, when the hypothalamus senses cold temperatures it triggers sympathetic discharge, resulting in the release of noradrenaline in brown adipose tissue and white adipose tissue. Acting via the β(3)-adrenergic receptors, noradrenaline induces lipolysis in white adipocytes, whereas it stimulates the expression of thermogenic genes, such as PPAR-γ coactivator 1a (Ppargc1a), uncoupling protein 1 (Ucp1) and acyl-CoA synthetase long-chain family member 1 (Acsl1), in brown adipocytes. However, the precise nature of all the cell types involved in this efferent loop is not well established. Here we report in mice an unexpected requirement for the interleukin-4 (IL-4)-stimulated program of alternative macrophage activation in adaptive thermogenesis. Exposure to cold temperature rapidly promoted alternative activation of adipose tissue macrophages, which secrete catecholamines to induce thermogenic gene expression in brown adipose tissue and lipolysis in white adipose tissue. Absence of alternatively activated macrophages impaired metabolic adaptations to cold, whereas administration of IL-4 increased thermogenic gene expression, fatty acid mobilization and energy expenditure, all in a macrophage-dependent manner. Thus, we have discovered a role for alternatively activated macrophages in the orchestration of an important mammalian stress response, the response to cold.

Nguyen KD, Qiu Y, Cui X et al, Nature. 2011 Nov 20;480(7375):104-8. doi: 10.1038/nature10653

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Role Of NUBC2/Nesfatin-1 In Glucose Control: Diverse Functions In Islets, Adipocytes And Brain.

Nakata M, Yada T. Curr Pharm Des. 2013 Mar 25. [Epub ahead of print]

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Mild cold exposure modulates fibroblast growth factor 21 (FGF21) diurnal rhythm in humans: relationship between FGF21 levels, lipolysis, and cold-induced thermogenesis.

Lee P et al, J Clin Endocrinol Metab. 2013 Jan;98(1):E98-102. doi: 10.1210/jc.2012-3107. Epub 2012 Nov 12.

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Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes.

Bordicchia M, Liu D, Amri EZ et al, J Clin Invest. 2012 Mar 1;122(3):1022-36. doi: 10.1172/JCI59701. Epub 2012 Feb 6.

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Interleukin-1β Downregulates RBP4 Secretion in Human Adipocytes.

Kotnik P et al, PLoS One. 2013;8(2):e57796. doi: 10.1371/journal.pone.0057796. Epub 2013 Feb 27.

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Intranasal application of the melanocortin 4 receptor agonist MSH/ACTH (4-10) in humans causes lipolysis in white adipose tissue.

Wellhöner P Int J Obes (Lond). 2012 May;36(5):703-8. doi: 10.1038/ijo.2011.105. Epub 2011 May 31.

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Catestatin (chromogranin A(352-372)) and novel effects on mobilization of fat from adipose tissue through regulation of adrenergic and leptin signaling.

Bandyopadhyay GK, Vu CU, Gentile S et al, J Biol Chem. 2012 Jun 29;287(27):23141-51. doi: 10.1074/jbc.M111.335877. Epub 2012 Apr 25.

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Bombesin receptor subtype-3 (BRS-3), a novel candidate as therapeutic molecular target in obesity and diabetes.

Ramos-Álvarez I, Martín-Duce A, Moreno-Villegas Z et al, Mol Cell Endocrinol. 2013 Mar 10;367(1-2):109-15. doi: 10.1016/j.mce.2012.12.025. Epub 2013 Jan 3.

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Neuropeptide Y impairs insulin-stimulated translocation of glucose transporter 4 in 3T3-L1 adipocytes through the Y1 receptor.

Gericke MT et al, Mol Cell Endocrinol. 2012 Jan 2;348(1):27-32. doi: 10.1016/j.mce.2011.07.028. Epub 2011 Jul 27.

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Cocaine- and amphetamine-regulated transcript is expressed in adipocytes and regulate lipid- and glucose homeostasis.

Banke E et al, BiochimRegul Pept. 2013 Mar 10;182:35-40. doi: 10.1016/j.regpep.2012.12.011. Epub 2013 Jan 11.

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Control of Adipogenesis by the Autocrine Interplays between Angiotensin (1-7) / Mas receptor and Angiotensin II / AT1 receptor Signaling Pathways.

Than A et al, J Biol Chem. 2013 Apr 16. [Epub ahead of print]

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Obestatin inhibits lipogenesis and glucose uptake in isolated primary rat adipocytes.

Pruszynska-Oszmalek E et al, J Biol Regul Homeost Agents. 2013 Jan-Mar;27(1):23-33.

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VPAC2-R mediates the lipolytic effects of pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal polypeptide in primary rat adipocytes.

Akesson L et al, Endocrinology. 2005 Feb;146(2):744-50. Epub 2004 Oct 28.

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Somatostatin is expressed and secreted by human adipose tissue upon infection and inflammation.

Seboek D et al, J Clin Endocrinol Metab. 2004 Oct;89(10):4833-9.

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Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21.

Possenti R, Muccioli G, Petrocchi P et al, Biochem J. 2012 Jan 1;441(1):511-22. doi: 10.1042/BJ20111165.

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Aldosterone Directly Affects Apelin Expression and Secretion in Adipocytes.

Jiang H, Ye X, Yang Z et al, J Mol Endocrinol. 2013 Apr 2. [Epub ahead of print]

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Pigment epithelium-derived factor associates with neuropathy and fibrosis in pancreatic cancer.

Samkharadze T, Erkan M, Reiser-Erkan C et al, Am J Gastroenterol. 2011 May;106(5):968-80. doi: 10.1038/ajg.2010.479. Epub 2011 Jan 11.


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