Acute orexin effects on insulin secretion in the rat: in vivo and in vitro studies

Nowak, Krzysztof W.; Maćkowiak, Paweł; Switonska, M.; Fabis, M.; Malendowicz, Ludwik K.

doi:10.1016/s0024-3205(99)00611-6

Cited by 115 publications

(57 citation statements)

References 8 publications

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“…This may serve to stimulate food intake. Also, an effect on plasma insulin has been confirmed by several approaches (25)(26)(27)(28); however, a strong link with glucagon secretion and glycemia is suggested by the present findings.…”

Section: Discussionsupporting

confidence: 50%

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: 50%

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

2003

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“…Orexin neurons, expressing both orexin and leptin receptors, have been identified in the gastrointestinal tract, and appear to be activated during starvation (Kirchgessner & Liu 1999). Orexin is also expressed in the endocrine cells in the gastric mucosa, intestine and pancreas (Kirchgessner & Liu 1999) and peripheral administration increases blood insulin levels (Nowak et al 2000).…”

Section: Dmhmentioning

confidence: 99%

Appetite control

Wynne¹,

Stanley²,

McGowan³

et al. 2005

Journal of Endocrinology

463

403

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Our understanding of the physiological systems that regulate food intake and body weight has increased immensely over the past decade. Brain centres, including the hypothalamus, brainstem and reward centres, signal via neuropeptides which regulate energy homeostasis. Insulin and hormones synthesized by adipose tissue reflect the long-term nutritional status of the body and are able to influence these circuits. Circulating gut hormones modulate these pathways acutely and result in appetite stimulation or satiety effects. This review discusses central neuronal networks and peripheral signals which contribute energy homeostasis, and how a loss of the homeostatic process may result in obesity. It also considers future therapeutic targets for the treatment of obesity.

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“…4 Peripherally administered orexin-A increases insulin secretion and results in increased blood glucose levels. 5 Orexins and orexin receptors are present in the hypothalamus as well as the enteric nervous system, the pancreas and the gut. 6 Leptin is another polypeptide important in regulating feeding behavior.…”

Section: Introductionmentioning

confidence: 99%

Decreased plasma orexin-A levels in obese individuals

et al. 2002

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Orexin-A and -B stimulate appetite and food intake in rats. Orexins and orexin receptors are present in the hypothalamus as well as the enteric nervous system, the pancreas and the gut. The presence of orexins in peripheral blood, however, has not yet been reported. To determine whether orexin-A is present in human plasma and is related to body weight, we measured plasma orexin-A and leptin levels in a population with a body mass index (BMI) range from 19.8 to 59 kg=m 2 . Plasma orexin-A levels correlated negatively and plasma leptin levels correlated positively with BMI. In obese and morbidly obese individuals, orexin-A levels were significantly lower and leptin levels were significantly higher when compared to normal. Our results support previous data suggesting that orexin-A acts also in a peripheral manner. The fact that lower levels of plasma orexin-A are present in obese individuals suggests that it is involved in the regulation of human energy metabolism.

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Acute orexin effects on insulin secretion in the rat: in vivo and in vitro studies

Cited by 115 publications

References 8 publications

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

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

Appetite control

Decreased plasma orexin-A levels in obese individuals

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