Secretion of soluble leptin receptors by exocrine and endocrine cells of the gastric mucosa

Leptin is a hormone secreted by the gastric mucosa into the lumen of the stomach. It is present in its intact form in the intestine where it regulates nutrient absorption and intestinal mucosa integrity. We have identified the binding protein that protects leptin from the harsh conditions of the gastric juice. Immunoprecipitations and Western blot analyses demonstrated that leptin is present in the gastric mucosa and the gastric juice, bound to a protein corresponding to the extracellular domain of the leptin receptor. In the absence of this soluble receptor, leptin is rapidly degraded. Immunocytochemistry on rat gastric mucosa identified the cells and intracellular compartments involved in secretion of this complex. Leptin receptor extracellular domain and leptin are present along the rough endoplasmic reticulum-Golgi-granules secretory pathways and form a complex in the secretory granules of Chief and specific endocrine cells. The long-form membrane leptin receptor OB-Rb, the protease activator furin, and proprotein convertase 7 were found in Chief cell granules but not in those of endocrine cells. The shedding of the receptor occurs in the immature granules. It is concluded that in the immature secretory granules of Chief cells, furin activates proprotein convertase 7 that, in turn, cleaves the extracellular portion of membrane-bound leptin receptors. Leptin bound to its soluble receptor forms a complex that is resistant to the gastric juice. Endocrine cells, on the other hand, generate a soluble leptin receptor by mechanisms different from those of the exocrine cells.

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Endocrine and Exocrine Secretion of Leptin by the Gastric Mucosa

Journal of Histochemistry & Cytochemistry ◽

10.1369/jhc.5a6620.2005 ◽

2005 ◽

Vol 53 (7) ◽

pp. 851-860 ◽

Cited By ~ 59

Author(s):

Philippe G. Cammisotto ◽

Christian Renaud ◽

Diane Gingras ◽

Edgard Delvin ◽

Emile Levy ◽

...

Keyword(s):

Gastric Mucosa ◽

Endocrine Cells ◽

Plasma Membranes ◽

Leptin Receptor ◽

Exocrine Secretion ◽

Double Immunostaining ◽

Leptin Receptors ◽

Short Forms ◽

Cell Plasma ◽

Two Populations

Leptin is a hormone that plays important roles in nutritional status and in obesity. By means of immunocytochemistry, two populations of leptin-secreting cells were found in the lower half of the gastric mucosa. One consists of numerous large cells located around the gastric pits, the Chief epithelial cells, whereas the second refers to much smaller cells, strongly stained, few in number, and scattered between the gastric pits, the endocrine cells. By double immunostaining, leptin and pepsinogen were colocalized in the Chief cells, whereas the endocrine cells were positive only for leptin. Immunoelectron microscopy showed that leptin is present along the rough endoplasmic reticulum–Golgi-granules secretory pathways of the Chief and endocrine cells. On the other hand, leptin-receptor (long and short forms) immunolabelings, although absent in the gastric epithelial cell plasma membranes, were present in enterocytes at the level of their apical and basolateral membranes. Duodenal, jejunal, and ileal enterocytes displayed similar labelings for the leptin receptor. Thus, exocrine and endocrine secretions of leptin together with the presence of leptin receptors on enterocyte plasma membranes constitute a gastroenteric axis that coordinates the role played by leptin in the digestive tract.

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The relationship between BMI, leptin, leptin receptors (LepR) and Foxp3+ Tregs cells in women with asthma

Diagnostyka Laboratoryjna ◽

10.5604/01.3001.0008.2513 ◽

2016 ◽

Vol 51 (4) ◽

pp. 277-284

Author(s):

Łukasz Kraszula ◽

Makandjou-Ola Eusebio ◽

Anna Jasińska ◽

Maciej Kupczyk ◽

Piotr Kuna ◽

...

Keyword(s):

Severe Asthma ◽

Leptin Receptor ◽

Control Group ◽

Soluble Receptor ◽

Leptin Receptors ◽

Global Initiative For Asthma ◽

Moderate Disease ◽

Global Initiative ◽

And Control ◽

The Relationship

The aim of this study was evaluation whether there is an association between BMI, leptin and its soluble receptor, the expression of FoxP3 in CD4+ pTreg in women with severe asthma. Materials and methods. The study included thirty women with asthma: 17 patients with severe and 13 with mild-moderate disease. The control group comprised of 25 healthy women. Asthma was diagnosed in accordance with the Global Initiative For Asthma guidelines (GINA 2014). The phenotype of CD4+CD25highCD127lowFoxp3+CD152+ cells was evaluated by multicolor flow cytometry. The concentration of leptin and its soluble receptor were determined using an immunoenzymatic method (ELISA). Results. It has been shown significantly increased leptin concentration in the group of women with severe asthma compared with mild-moderate asthma and control group (p <0.05). The concentration of the leptin receptor significantly increased (p <0.05) in women with severe asthma compared with control group. There were no differences in percentage of CD4+FoxP3+ and CD4+CD25highCD127low- FoxP3+CD152+ subsets after leptin stimulation in all tested groups. Conclusions. Our results don’t confirm the direct effect of leptin on the CD4+ pTreg cells and the expression of FoxP3 in these cells, in tested groups.

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Faculty Opinions recommendation of Secretion of soluble leptin receptors by exocrine and endocrine cells of the gastric mucosa.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.8370.465858 ◽

2006 ◽

Author(s):

Ian Beales

Keyword(s):

Gastric Mucosa ◽

Endocrine Cells ◽

Leptin Receptors

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Transfer and distribution of amoxicillin in the rat gastric mucosa and gastric juice and the effects of rabeprazole

Acta Pharmacologica Sinica ◽

10.1038/aps.2009.191 ◽

2010 ◽

Vol 31 (4) ◽

pp. 501-508 ◽

Cited By ~ 5

Author(s):

Hai-lun Zheng ◽

Yong-mei Hu ◽

Jun-jun Bao ◽

Jian-ming Xu

Keyword(s):

Gastric Mucosa ◽

Gastric Juice ◽

Rat Gastric Mucosa

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Histamine-storing cells in the oxyntic mucosa of the rat stomach: a transmission electron microscopic study employing fixation with carbodiimide.

Journal of Histochemistry & Cytochemistry ◽

10.1177/41.9.8354880 ◽

1993 ◽

Vol 41 (9) ◽

pp. 1405-1412 ◽

Cited By ~ 16

Author(s):

M J Nissinen ◽

P Panula

Keyword(s):

Gastric Mucosa ◽

Endocrine Cells ◽

Cell Types ◽

Rat Stomach ◽

Electron Microscopic ◽

Oxyntic Mucosa ◽

Ecl Cells ◽

Transmission Electron ◽

Basal Half ◽

Rat Gastric Mucosa

We studied the distribution of histamine (HA) immunoreactivity in endocrine cells of the acid-producing mucosa in rat stomach with pre-embedding immunoelectron microscopy (IEM) using an antiserum against HA. Four fixation modifications were compared to optimize the ultrastructural morphology and staining pattern with the antisera produced against carbodiimide-conjugated HA. Fixation with 4% 1-ethyl-3(3-dimethyl-aminopropyl) carbodiimide (EDCDI) combined with both 4% paraformaldehyde and 0.1% glutaraldehyde gave superior results compared with EDCDI alone. Enterochromaffin-like (ECL) cells were easily distinguished from other endocrine cells in optimally fixed samples. The peroxidase end-product was distributed within the cytoplasm surrounding the vesicles of the ECL cells. ECL cells comprised about 75% of all endocrine cells, and about 90% of them were HA immunoreactive (HA-IR). No other HA-IR cell types were identified by EM in the basal half of the oxyntic region of rat gastric mucosa. The results suggest that a combination of EDCDI and aldehydes is suitable for IM demonstration of HA in cells. ECL cells from a predominant portion of endocrine cells in the oxyntic glands and may constitute the only significant non-mast cell store of HA in rat gastric mucosa.

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