Gastric inhibitory polypeptide and glucagon-like peptide-1(7–36) amide exert similar effects on somatostatin secretion but opposite effects on gastrin secretion from the rat stomach

Jia, Xiaoyan; Brown, John C.; Kwok, Yin Nam; Pederson, Raymond A.; McIntosh, C. H. S.

doi:10.1139/y94-172

Cited by 26 publications

(16 citation statements)

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“…was not carried out, but preliminary data suggest that acute as well as subchronic peripheral administration of NN2211 reduces meal size similar to what is known for other gastrointestinal hormones, such as CCK (22,23; P.J.L., unpublished observations). It has been suggested that signals that modify food intake via diminishing meal size are both direct and indirect (23).…”

Section: Discussionmentioning

confidence: 78%

“…Thus, it seems likely that the anorectic effect of peripheral GLP-1 is mediated via a peripherally accessible site located either in the brainstem or on vagal afferents. In rats, the inhibitory actions of GLP-1 on gastric motility is mediated via the vagus nerve (11), but also direct inhibition of gastrin secretion as well as stimulation of somatostatin release may affect gastric emptying (21,22). Obviously, delayed gastric emptying coun- teracts excessive meal-related glucose excursions with consequent beneficial glucose homeostatic effects.…”

Section: Discussionmentioning

confidence: 99%

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Systemic Administration of the Long-Acting GLP-1 Derivative NN2211 Induces Lasting and Reversible Weight Loss in Both Normal and Obese Rats

et al. 2001

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Postprandial release of the incretin glucagon-like peptide-1 (GLP-1) has been suggested to act as an endogenous satiety factor in humans. In rats, however, the evidence for this is equivocal probably because of very high endogenous activity of the GLP-1 degrading enzyme dipeptidyl peptidase-IV. In the present study, we show that intravenously administered GLP-1 (100 and 500 g/kg) decreases food intake for 60 min in hungry rats. This effect is pharmacologically specific as it is inhibited by previous administration of 100 g/kg exendin(9-39), and biologically inactive GLP-1(1-37) had no effect on food intake when administered alone (500 g/kg). Acute intravenous administration of GLP-1 also caused dose-dependent inhibition of water intake, and this effect was equally well abolished by previous administration of exendin(9-39). A profound increase in diuresis was observed after intravenous administration of both 100 and 500 g/kg GLP-1. Using a novel longacting injectable GLP-1 derivative, NN2211, the acute and subchronic anorectic potentials of GLP-1 and derivatives were studied in both normal rats and rats made obese by neonatal monosodium glutamate treatment (MSG). We showed previously that MSG-treated animals are insensitive to the anorectic effects of centrally administered GLP-1(7-37). Both normal and MSGlesioned rats were randomly assigned to groups to receive NN2211 or vehicle. A single bolus injection of NN2211 caused profound dose-dependent inhibition of overnight food and water intake and increased diuresis in both normal and MSG-treated rats. Subchronic multiple dosing of NN2211 (200 g/kg) twice daily for 10 days to normal and MSG-treated rats caused profound inhibition of food intake. The marked decrease in food intake was accompanied by reduced body weight in both groups, which at its lowest stabilized at ϳ85% of initial body weight. Initial excursions in water intake and diuresis were transient as they were normalized within a few days of treatment. Lowered plasma levels of triglycerides and leptin were observed during NN2211 treatment in both normal and MSG-treated obese rats.In a subsequent study, a 7-day NN2211 treatment period of normal rats ended with measurement of energy expenditure (EE) and body composition determined by indirect calorimetry and dual energy X-ray absorptiometry, respectively. Compared with vehicle-treated rats, NN2211 and pair-fed rats decreased their total EE corresponding to the observed weight loss, such that EE per weight unit of lean body mass was unaffected. Despite its initial impact on body fluid balance, NN2211 had no debilitating effects on body water homeostasis as confirmed by analysis of body composition, plasma electrolytes, and hematocrit. This is in contrast to pair-fed animals, which displayed hemoconcentration and tendency toward increased percentage of fat mass. The present series of experiments show that GLP-1 is fully capable of inhibiting food intake in rats via a peripherally accessible site. The loss in body weight is accompanied by decreased levels of ci...

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Systemic Administration of the Long-Acting GLP-1 Derivative NN2211 Induces Lasting and Reversible Weight Loss in Both Normal and Obese Rats

et al. 2001

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“…Because direct arterial infusion of GLP-1 did not inhibit antral or pyloric motor activity in dogs, a direct effect of GLP-1 on gastric smooth muscle seems unlikely (6). Although GLP-1 can release somatostatin (24), which increases fasting gastric volume (13), the inhibitory effect of GLP-1 on fasting small bowel motility is not mediated by somatostatin (46). In rats, GLP-1 increases blood pressure and heart rate and reduces intestinal motility via sympathetic stimulation (50,51).…”

Section: Discussionmentioning

confidence: 96%

“…This research was presented in abstract form at the American Motility Society Meeting, Santa Monica, CA, September [22][23][24][25] 2005. …”

Section: Acknowledgmentsmentioning

confidence: 99%

Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults

Andrews

Bharucha²,

Camilleri³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Zinsmeister AR. Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults. Am J Physiol Gastrointest Liver Physiol 292: G1359 -G1365, 2007. First published February 8, 2007 doi:10.1152/ajpgi.00403.2006.-The incretin glucagon-like peptide-1 (GLP-1), which is used to treat diabetes mellitus, delays gastric emptying by inhibiting vagal activity. GLP-1 also increases fasting and postprandial gastric volume in humans. On the basis of animal studies, we hypothesized that nitric oxide mediates the effects of GLP-1 on gastric volumes. To assess the effects of nitrergic blockade on GLP-1-induced gastric accommodation in humans, in this double-blind study, 31 healthy volunteers were randomized to placebo (i.e., saline), GLP-1, or the nitric oxidealone or with GLP-1. Thereafter, 16 additional subjects were randomized to GLP-1 alone or together with a higher dose of L-NMMA (10 mg/kg bolus plus 8 mg ⅐ kg Ϫ1 ⅐ h Ϫ1 infusion). Gastric volumes (fasting pre-and postdrug, postprandial postdrug) were measured by 99m Tc-single-photon-emission computed tomography imaging. GLP-1 increased (P ϭ 0.04) fasting gastric volume by 83 Ϯ 16 ml (vs. 17 Ϯ 11 ml for placebo) and augmented (P Յ 0.01) postprandial accommodation by 688 Ϯ 165 ml (vs. 542 Ϯ 29 ml for placebo). L-NMMA (low dose) alone did not affect fasting or postprandial gastric volume. L-NMMA (low dose) did not attenuate the effect of GLP-1 on gastric volumes. In contrast, L-NMMA (high dose) did not affect fasting volume but blunted GLP-1-mediated postprandial accommodation (postprandial change ϭ 494 Ϯ 37 ml, P Յ 0.01 vs. GLP-1 alone). These data are consistent with the hypothesis that nitric oxide partly mediates the effects of GLP-1 on postprandial but not fasting gastric volumes in humans. accommodation; stomach; postprandial; diabetes; vagus GLUCAGON-LIKE PEPTIDE-1 (GLP-1) is an incretin produced by enteroendocrine L cells throughout the small intestine (45). The GLP-1 agonist exendin-4 improves glycemic control in patients with Type 2 diabetes mellitus inadequately treated with oral hypoglycemic agents (20). GLP-1 reduces postprandial glycemia not only by its hormonal effects (i.e., reduced glucagon and increased insulin release) (20, 29), but also by its powerful effects on gastrointestinal (GI) motility and secretion (31). Thus GLP-1 is a mediator of the ileal brake, delays gastric emptying, increases gastric volume, and reduces gastric acid secretion in humans (8,40,41). These GI effects of GLP-1 may also contribute to its side effects at pharmacological concentrations. For example, in a multicenter study of 551 patients with inadequately controlled Type 2 diabetes mellitus, 57% of patients treated with a GLP-1 agonist reported nausea and 17% reported vomiting, and GLP-1 was discontinued because of these side effects in 6% of patients (18).An intact vagus nerve is necessary for GLP-1 to delay gastric emptying in rats and pigs (21, 48) and to inhibit acid secretion in humans (49). GLP-1 also inhibits the plasma pancreatic pol...

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“…GIP 1-42 is known to promote somatostatin release from the stomach (15,24,26). To determine whether amidated GIP has similar potency as GIP , we performed an in situ perfusion study using a vascularly perfused isolated mouse stomach preparation.…”

Section: Furin Is Likely Not Involved In Pro-gip Processingmentioning

confidence: 99%

Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut

Fujita

Asadi

Yang

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Glucose-dependent insulinotropic polypeptide (GIP) is a hormone released from enteroendocrine K cells in response to meals. Posttranslational processing of the precursor protein pro-GIP at residue 65 by proprotein convertase subtilisin/kexin type 1 (PC1/3) in gut K cells gives rise to the established 42-amino-acid form of GIP (GIP1–42). However, the pro-GIP peptide sequence contains a consensus cleavage site for PC2 at residues 52–55 and we identified PC2 immunoreactivity in a subset of K cells, suggesting the potential existence of a COOH-terminal truncated GIP isoform, GIP1–30. Indeed a subset of mouse and human K cells display GIP immunoreactivity with GIP antibodies directed to the mid portion of the peptide, but not with a COOH-terminal-directed GIP antibody, indicative of the presence of a truncated form of GIP. This population of cells represents ∼5–15% of the total GIP-immunoreactive cells in mice, depending on the region of intestine, and is virtually absent in mice lacking PC2. Amidated GIP1–30 and GIP1–42 have comparable potency at stimulating somatostatin release in the perfused mouse stomach. Therefore, GIP1–30 represents a naturally occurring, biologically active form of GIP.

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Gastric inhibitory polypeptide and glucagon-like peptide-1(7–36) amide exert similar effects on somatostatin secretion but opposite effects on gastrin secretion from the rat stomach

Cited by 26 publications

References 0 publications

Systemic Administration of the Long-Acting GLP-1 Derivative NN2211 Induces Lasting and Reversible Weight Loss in Both Normal and Obese Rats

Systemic Administration of the Long-Acting GLP-1 Derivative NN2211 Induces Lasting and Reversible Weight Loss in Both Normal and Obese Rats

Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults

Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut

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