Immunoreactive orexin-A in human plasma

Arihara, Zenei; Takahashi, Kazuhiro; Murakami, Osamu; Totsune, Kazuhito; Sone, Masahiko; Satoh, Fumitoshi; Ito, Sadayoshi; Mouri, Toraichi

doi:10.1016/s0196-9781(00)00369-7

Cited by 92 publications

(67 citation statements)

References 23 publications

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“…Thus, orexin cells are somehow sensing the animal's nutritional state, and OXA is released in response to nutritional depletion. In support of this idea, we found a significant increase in plasma OXA level in fasted lean rats similar to that reported in humans (14,15). The origin of plasma OXA was not identified; however, in light of the present findings, one potential source is the pancreatic islets.…”

Section: Discussionsupporting

confidence: 90%

supporting

confidence: 54%

“…Endocrine cells in the gastric and intestinal mucosa (12,13), as well as in the pancreas (12), also contain orexins; therefore, orexins may function as circulating hormones and/or paracrine or autocrine transmitters. The presence of OXA in human plasma supports this idea (14,15).Little is known about the regulation and role of the orexins in the endocrine pancreas. We have previously shown that OXA and orexin receptor immunoreactivity is displayed by the insulin-secreting ␤-cells in the rat pancreas (12).…”

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confidence: 79%

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Glucose Regulates the Release of Orexin-A From the Endocrine Pancreas

2003

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Orexins (hypocretins) are novel neuropeptides that appear to play a role in the regulation of energy balances. Orexin-A (OXA) increases food intake in rodents, and fasting activates OXA neurons in both the lateral hypothalamic area and gut. OXA is also found in the endocrine pancreas; however, little is known about its release or functional significance. In this study, we show that depolarizing stimuli evoke the release of OXA from rat pancreatic islets in a calcium-dependent manner. Moreover, OXA release is stimulated by low glucose (2.8 mmol/l), similar to glucagon secretion, and inhibited by high glucose (16.7 mmol/l). Fasting increases plasma OXA, supporting the idea that orexin is released in response to hypoglycemia. Cells that secrete glucagon and insulin contain OXA and both cell types express orexin receptors. OXA increases glucagon secretion and decreases glucose-stimulated insulin release from isolated islets. OXA infusion increases plasma glucagon and glucose levels and decreases plasma insulin in fasted rats. We conclude that orexin-containing islet cells, like those in the brain and gut, are glucosensitive and part of a network of glucose "sensing" cells that becomes activated when blood glucose levels fall. OXA may modulate islet hormone secretion to maintain blood glucose levels during fasting. Diabetes 52: 111-117, 2003 O rexins (hypocretins) are novel neuropeptides that play a role in arousal and the regulation of energy balances (1-3). Orexin-A (OXA) and -B are 33-and 28-residue peptides, respectively, that are isolated from the rat hypothalamus and named for their ability to stimulate feeding when injected into the brain (2). Their common precursor, prepro-orexin, is expressed in a specific population of neurons in and around the lateral hypothalamic area (LHA) (2), a region classically implicated in the control of mammalian feeding behavior (4). The LHA contains glucosensitive neurons that are stimulated by falls in circulating glucose (5) and inhibited by prandial signals, such as the presence of food in the gut and/or a rise in portal glucose concentration (4). Previous studies have suggested that orexin neurons might correspond to this neuronal population, since orexin neurons are activated by hypoglycemia (6) and increased hypothalamic prepro-orexin mRNA levels are observed in response to fasting (1,7); however, glucosensitive neurons do not contain OXA (8). They are excited by the peptide (8), implying that orexin acts as a neuromodulator at glucosensitive cells, stimulating them under conditions of hunger.Glucosensitive neurons are also found in regions outside the hypothalamus, including the nucleus of the solitary tract (NTS) (9) and enteric nervous system (ENS) (10). The NTS relays visceral afferent signals to the LHA (8). Orexin fibers are distributed extensively in the NTS (11), and glucosensitive neurons are activated by the same conditions that stimulate orexin neurons in the LHA (6). The ENS participates in the regulation of food intake by directly sensing, integrating, and reg...

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Section: Discussionsupporting

confidence: 90%

supporting

confidence: 54%

mentioning

confidence: 79%

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Glucose Regulates the Release of Orexin-A From the Endocrine Pancreas

2003

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“…Orexins and their receptors (orexin 1 R and orexin 2 R) were initially identified in the brain (Sakurai 1999). Recent data have shown that many peripheral tissues express orexin receptors (orexin 1 R and orexin 2 R) (Johren et al 2001) and there is detectable orexin-A in the circulation (Arihara et al 2001). These data imply that circulating orexin-A may have some physiological actions, especially in the regulation of feeding and sleeping.…”

Section: Introductionmentioning

confidence: 99%

Central and/or peripheral immunoreactivity of orexin-A in pregnant rats and women

Sun

Tian²,

Yao³

et al. 2006

Journal of Molecular Endocrinology

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Orexins (A and B) have been implicated in feeding behavior, energy balance and state of vigilance. During pregnancy, their involvement in feeding regulation and reproduction are poorly understood. In this study, we investigated orexin-A immunoreactivity in the hypothalamus and serum in pregnant rats and women by immunofluorescence staining, image analysis and radioimmunoassay, examined the correlation of serum orexin-A and leptin with gestational age in pregnant women by regression analysis, and explored the effect of leptin injected intracerebroventricularly (i.c.v.) on orexin-A immunoreactivity in the hypothalamus of normal rats by immunohistochemistry. The results showed that pregnant rats had significantly greater daily food intake on days 15 and 20 of pregnancy than virgin ones (+27·3%, P<0·01 and +38·6%, P<0·001 respectively), with significantly fewer number and lower mean staining intensity of orexin-A-immunoreactive (ir) neurons on days 16 (both P<0·05) and 21 (both P<0·01) of pregnancy. Moreover, serum levels of orexin-A exhibited 2·0-fold and 2·2-fold increases (both P<0·001) in rats on days 16 and 21 of pregnancy compared with those in virgin rats, and 1·9-fold and 2·0-fold increases (both P<0·001) in mid (13-26 weeks) and late pregnant women (27-40 weeks) compared with those in non-pregnant women. Simultaneously, serum levels of leptin showed a 2·3-fold and 2·2-fold increase (both P<0·001) in rats on days 16 and 21 of pregnancy, and a 3·3-fold and 4·3-fold increase (both P<0·001) in mid and late pregnant women. Serum levels of both orexin-A and leptin correlated positively with gestational age in pregnant women. Leptin injected i.c.v. significantly decreased the number (P<0·01) and mean staining intensity (P<0·01) of orexin-A-ir neurons in the hypothalamus, food intake (P<0·01) and body weight gain (P<0·001) compared with vehicle injection in normal rats. These results suggested that central and serum orexin-A might be involved in the regulation of feeding and energy metabolism during pregnancy. The change in central orexin-A immunoreactivity might be related to the increased serum leptin concentrations.

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“…Consistent experimental findings showed that orexins may enhance glucocorticoid secretion acting not only on the central branch of the HPA axis but also directly on adrenocortical cells that are provided with orexin receptors. However, the relevance of the latter mechanism of action of orexins remains questionable: in fact, 1) the level of circulating orexin-A in rat and humans does not exceed 15 and 2 pmol/l (Arihara et al, 2001;Jöhren et al, 2001Jöhren et al, , 2003; 2) minimal effective concentrations of orexin-A in eliciting in vitro glucocorticoid secretagogue effect are approximately 10 Ϫ8 and 10 Ϫ10 M in rats and humans (see section IV.B.2. ); and 3) no measurable concentrations of orexins are present in normal adrenal glands (see section IV.A.1.…”

Section: Discussionmentioning

confidence: 99%