Modulation of exocrine pancreatic secretion by leptin through CCK1-receptors and afferent vagal fibres in the rat

Guilmeau, Sandra; Nagain-Domaine, C.; Buyse, Marion; Tsocas, Annick; Rozé, C; Bado, André

doi:10.1016/s0014-2999(02)01887-3

Cited by 17 publications

(11 citation statements)

References 40 publications

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“…Previous studies have shown that CCK-1 receptor antagonists can prevent the peripheral leptin-induced inhibition of food intake (10) and the stimulation of pancreatic exocrine secretions (11), which suggests that CCK is involved. However, whether leptin modulates the release of CCK is unknown.…”

Section: Discussionmentioning

confidence: 93%

“…Cholecystokinin (CCK) is secreted from duodenal endocrine I cells and typically functions as one of these short-term satiety signals (8,9). Interestingly, the leptin-induced inhibition of food intake (10) and the stimulation of pancreatic exocrine secretions (11) can be blocked by a CCK-1 receptor antagonist. These data suggest that endogenous CCK is involved in these effects, operating through CCK-1 receptors.…”

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confidence: 99%

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Duodenal Leptin Stimulates Cholecystokinin Secretion

Guilmeau

Buyse²,

Tsocas³

et al. 2003

Diabetes

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Some of the actions of leptin depend on cholecystokinin (CCK). However, it is unknown whether leptin modulates the release of CCK. Here, we demonstrate in vitro that leptin induces the phosphorylation of extracellular signal-related kinase (ERK)-1/2 proteins and increases CCK release (EC 50 ‫؍‬ 0.23 nmol/l) in CCK-secreting STC-1 cells. We showed that rat duodenal juice contains leptin that circulates free and bound to macromolecules, suggesting that leptin has a lumenal action on the intestine. In vivo in the rat, duodenal infusion of leptin increased plasma CCK at levels comparable to those induced by feeding. Moreover, meal-induced increases in plasma CCK were markedly reduced in obese fa/fa rats, whereas the mobilization of the gastric leptin pool was similar in lean and obese Zucker rats. L eptin, the ob gene product, was initially reported to be produced by adipose cells (1). It is released into the bloodstream and transported across the blood-brain barrier into the hypothalamus, where it activates specific leptin receptors (2,3) and regulates energy homeostasis by altering energy intake and expenditure (4 -6). Leptin regulates food intake by mechanisms involving cross-talk between hypothalamic leptin receptors and various neuropeptides involved in the control of feeding. The leptin receptor (Ob-R) is a member of the gp130 family of cytokine receptors. It occurs in several isoforms resulting from the alternative splicing of the db leptin receptor gene (2,3). It is currently thought that the long isoform, Ob-Rb, can activate the signal transducers and activators of transcription (STAT) pathways, whereas both Ob-Rb and the short isoform (Ob-Ra) can transduce signals through insulin receptor substrates and through mitogen-activated protein kinase (MAPK) pathways (7).The signals that arise from the upper gastrointestinal tract upon feeding are transmitted to the brain by the vagus nerve. These signals are key components in the control of meal-induced satiety. Cholecystokinin (CCK) is secreted from duodenal endocrine I cells and typically functions as one of these short-term satiety signals (8,9). Interestingly, the leptin-induced inhibition of food intake (10) and the stimulation of pancreatic exocrine secretions (11) can be blocked by a CCK-1 receptor antagonist. These data suggest that endogenous CCK is involved in these effects, operating through CCK-1 receptors. However, it is not currently known whether leptin directly modulates the release of CCK.Leptin is also produced by the stomach (12-14) and is mainly secreted into the gastric juice after CCK in rats (12,15) and after secretin or vagal stimulation in humans (14,16). Some of the stomach-derived leptin is not fully degraded by proteolysis, indicating that it reaches the intestine in an active form and thus can initiate biological processes controlling functions of the intestinal tract. Indeed, lumenal leptin increases the activity of the brush border proton-dependent transporter, PepT1, which enhances the intestinal absorption of oligopeptides (17). T...

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Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

Duodenal Leptin Stimulates Cholecystokinin Secretion

Guilmeau

Buyse²,

Tsocas³

et al. 2003

Diabetes

Self Cite

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“…Very recent studies have also demonstrated that Ob-Rb is present in rat, mouse, and human small intestinal enterocytes (30), where it may play a role in fat (43) and small-peptide (44) absorption. Leptin was also shown to stimulate the secretion of the gastrointestinal hormones gastrin (45) and cholecystokinin (46) in vivo in rats. The present study suggests an additional role for leptin in the intestine, to regulate glucose homeostasis through its effects on GLP-1 secretion.…”

Section: Discussionmentioning

confidence: 98%

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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“…However, in the same study administration of leptin led to decrease of protein output in PBJ but had no effect on amylase release from pancreatic acini in vitro. In contrast, in study of Guilmeau et al (2002) exogenous leptin administration (30-100 nmol -1 kg BW) produced dose related increase of volume, protein and bicarbonates output in PBJ. In the same study it was shown that high doses of leptin can release CCK, and it is possible that leptin effect on PBJ was indirect.…”

Section: Resultsmentioning

confidence: 77%

“…Leptin administration decreased (Bilski et al, 2000;Matyjek et al, 2003) or increased (Guilmeau et al, 2002) pancreato-biliary secretion (PBJ) in anaesthetized rats. Harris et al (1999) reported an CCK dependent increase of amylase release from cultured rat pancreas cancer line cells in vitro.…”

Section: Introductionmentioning

confidence: 99%

Exogenous leptin does not affect exocrine pancreatic secretion in conscious sheep

Korczyński¹,

Kirat²,

Kato³

2004

J. Anim. Feed Sci.

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The experiment was performed on 10 Black Suffolk sheep of 59 ± 8 kg BW. The animals were equipped with two catheters in common bile duct and one in duodenum and set of three bipolar electrodes sutured on the duodenum. In accordance to duodenal electromyography activity, effect of exogenous leptin on pancreatic juice secretion was studied. Administration of leptin (2-10 µg kg -1 BW intravenously) did not affect the volume, protein, amylase and bicarbonates output in pancreatic juice. In conclusion, the results suggest, that in the doses used, leptin have no effect on pancreatic secretion.

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Modulation of exocrine pancreatic secretion by leptin through CCK1-receptors and afferent vagal fibres in the rat

Cited by 17 publications

References 40 publications

Duodenal Leptin Stimulates Cholecystokinin Secretion

Duodenal Leptin Stimulates Cholecystokinin Secretion

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

Exogenous leptin does not affect exocrine pancreatic secretion in conscious sheep

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