Leptin secretion and leptin receptor in human stomach

Sobhani, Iradj; Vissuzaine, C; Buyse, Marion; Kermorgant, Stéphanie; Laigneau, Jean–Pierre; Hénin, Dominique; Bado, André; Lewin, Miguel JM

doi:10.1016/s0016-5085(00)82203-9

Cited by 46 publications

(61 citation statements)

References 12 publications

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“…The concentration of the cytokine in distinct granula is in line with the immunohistochemical localisation of leptin in other tissues (Tsuruo et al 1996, Cinti et al 1997, Sobhani et al 2000. This leads to our hypothesis that the peptide is stored within the glandular cells before its release into saliva.…”

Section: Discussionsupporting

confidence: 75%

Differential distribution and expression of leptin and the functional leptin receptor in major salivary glands of humans

Bohlender¹,

Rauh²,

Zenk³

et al. 2003

Journal of Endocrinology

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Leptin plays a central role in the regulation of food intake and energy expenditure in rodents. However, it has become clear that this hormone has more than only a satiety-inducing function, and that there are other sources of leptin, such as the central nervous system, placenta and the gastrointestinal tract in addition to adipose tissue. Knowing about the important role of the salivary glands in food intake and digestion, it was the objective of the present study to investigate how leptin and its receptor are expressed and distributed in the major salivary glands of humans. We found leptin distributed throughout the major salivary glands with obvious intracellular concentrations in granula. In contrast, immunostaining for the leptin receptor was found exclusively in the membranes of the glandular cells. A high density of the leptin receptor was localised in the epithelia of the duct lumen. PCR analysis proved the autonomous expression of leptin by the salivary glands independently from adipocytes. Accordingly the long receptor isoform was expressed by any examined tissue. In the light of recent findings of leptin influencing the growth of rodent salivary glands, the presence and distribution of leptin and its receptor suggests an autocrine role of salivary leptin within the glands.

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Section: Discussionsupporting

confidence: 75%

Differential distribution and expression of leptin and the functional leptin receptor in major salivary glands of humans

Bohlender¹,

Rauh²,

Zenk³

et al. 2003

Journal of Endocrinology

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“…As a consequence, GLP-1 release is biphasic, with the indirect effects occurring rapidly (15-30 min) and the direct effects taking place much later (60 -120 min) after a meal (4,5). Although leptin is normally released from adipose tissue 60 -120 min postprandially (55), recent studies have demonstrated that leptin is also synthesized by the gastric chief cells (31,56), and release of gastric leptin occurs 15 min after refeeding in a fasted rat (56). Thus, gastric leptin may be involved in the early indirect regulation of GLP-1 secretion by neuronal media- tors such as GRP, whereas leptin from the adipocyte may be more important in the maintenance of basal levels and the later postprandial phase of GLP-1 release.…”

Section: Discussionmentioning

confidence: 99%

Role of Leptin in the Regulation of Glucagon-Like Peptide-1 Secretion

2003

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T he hormone glucagon-like peptide-1 (GLP-1) is secreted from enteroendocrine L cells, which are localized in the distal ileum and colon (1), after nutrient ingestion (2-5). GLP-1 acts through a specific G-protein-coupled receptor to potently stimulate glucose-dependent insulin secretion (6 -8). GLP-1 further reduces glycemia through inhibition of both glucagon secretion (9) and gastric emptying (10) and by stimulation of pancreatic ␤-cell proliferation and neogenesis (11,12). The GLP-1 receptor is also expressed in hypothalamic nuclei that are responsible for modulating feeding behavior (13,14), and central GLP-1 administration reduces food intake in rodents, whereas peripheral administration of GLP-1 promotes satiety and decreases body weight in humans (13,15). These pleiotropic actions of GLP-1 therefore offer great potential for the treatment of hyperglycemia in patients with type 2 diabetes (1,15).It has recently been shown that plasma GLP-1 levels are reduced in obesity (16 -19), a condition that is highly correlated to type 2 diabetes (20). The mechanisms leading to decreased GLP-1 secretion in obesity have not been elucidated. However, because plasma leptin levels are proportional to fat mass, we postulated the existence of an adipo-enteroendocrine interaction between leptin and GLP-1. Leptin, a product of the ob gene in white adipose tissue, activates hypothalamic circuits, leading to the inhibition of food intake (21,22). The leptin receptor gene encodes five alternatively spliced forms of mRNA (23,24). However, only the long form of the leptin receptor (ObRb) contains an intracellular JAK-STAT signaling motif, and Ob-Rb appears to be responsible for the physiological actions of leptin (25-27). Although Ob-Rb is predominantly distributed in the ventral medial hypothalamic region known to be important in determining feeding behavior (21,28), it is now recognized that Ob-Rb is also expressed in several peripheral tissues, including the gut and the pancreas (29 -31).It has been shown that ob/ob mice, which are homozygous for a mutation of the ob gene, and db/db mice, which have a mutation in the leptin receptor, both exhibit hyperphagia and morbid obesity, leading to hyperinsulinemia and hyperglycemia (22,23). Although ob/ob and db/db mice serve as models of type 2 diabetes, human ob or db gene mutations are extremely rare, and no linkages with diabetes have been found (32,33). Nonetheless, most obese humans exhibit hyperleptinemia, and increased adiposity is believed to occur in association with the development of leptin resistance (21,32,33). One model of leptin resistance is the C57BL/6 mouse submitted to a high-fat diet (34). In contrast to the ob/ob and db/db mice, these mice develop impaired glucose tolerance but seldom progress to frank diabetes. We now demonstrate that leptin stimulates GLP-1 secretion from enteroendocrine L cells in vitro and in vivo and, furthermore, that leptin resistance in obese C57BL/6 mice is associated with impaired secretion of GLP-1. RESEARCH DESIGN AND METHODSCell cultu...

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“…Therefore, there is a possibility that endogenously secreted leptin does not reach a sufficient concentration to transactivate EGFR in vitro. Another explanation is that, as for gastric leptin, some stimulation, such as by pentagastrin (19), secretin (19), or cholecystokinin (5), is needed for leptin secretion, which is different from adipose cells, which are not believed to store leptin (5). Therefore, whereas gastric cells constitutively express leptin, they may not automatically secrete leptin without any stimulation.…”

Section: Discussionmentioning

confidence: 99%

Transactivation of Epidermal Growth Factor Receptor Is Involved in Leptin-Induced Activation of Janus-Activated Kinase 2 and Extracellular Signal–Regulated Kinase 1/2 in Human Gastric Cancer Cells

et al. 2005

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Leptin is known to act as a growth factor through the Janusactivated kinase (JAK)/signal transducer and activator of transcription signaling pathway as well as the mitogenactivated protein kinase pathway. In this study, we showed a novel signal transduction pathway using two human gastric cancer cell lines, MKN28 and MKN74. Both gastric cancer cells expressed leptin and its receptors (Ob-R) at the protein level. We found that leptin, even at as low as 0.1 ng/mL, induced significant tyrosine phosphorylation of epidermal growth factor receptor (EGFR). Time-course experiments revealed that phosphorylation was maximal after 5 minutes of stimulation and declined thereafter. We also revealed that tyrosine phosphorylation of EGFR induced by leptin was significantly attenuated by two inhibitors, an EGFR tyrosine kinase inhibitor, AG1478, and a broad-spectrum matrix metalloproteinase inhibitor, GM6001. This indicates that the pathway of EGFR transactivation induced by leptin is dependent on proteolytically released EGFR ligands. Leptin induced JAK2 activation and extracellular signal-regulated kinase (ERK) 1/2 activation in these gastric cancer cells, both of which occurred after the peak of EGFR transactivation. Pretreatment of gastric cancer cells with AG1478 significantly reduced the degree of phosphorylation of both JAK2 and ERK1/2. These findings indicate the involvement of EGFR transactivation in the activation of JAK2 and ERK1/2. Our results reveal that EGFR transactivation is involved in the leptin signaling pathway in gastric cancer cells, which extends the physiologic action of leptin beyond its central effects in the hypothalamus to regulate body weight. (Cancer Res 2005; 65(20): 9159-63)

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Leptin secretion and leptin receptor in human stomach

Cited by 46 publications

References 12 publications

Differential distribution and expression of leptin and the functional leptin receptor in major salivary glands of humans

Differential distribution and expression of leptin and the functional leptin receptor in major salivary glands of humans

Role of Leptin in the Regulation of Glucagon-Like Peptide-1 Secretion

Transactivation of Epidermal Growth Factor Receptor Is Involved in Leptin-Induced Activation of Janus-Activated Kinase 2 and Extracellular Signal–Regulated Kinase 1/2 in Human Gastric Cancer Cells

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