Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects

Greenfield, Jerry R.; Farooqi, I. Sadaf; Keogh, Julia M.; Henning, Elana; Habib, Abdella M.; Blackwood, Anthea; Reimann, Frank; Holst, Jens J.; Gribble, Fiona M.

doi:10.3945/ajcn.2008.26362

Cited by 208 publications

(211 citation statements)

References 29 publications

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“…Single L-amino acids, including L-Glu, increased GLP-1 release from cultured enteroendocrine-like GLUTag cells (Reimann et al, 2004). In humans, oral glutamine increased circulating GLP-1 concentration at similar concentrations to oral glucose (Greenfield et al, 2009). In contrast, purified L cells from transgenic mice with green fluorescent protein-tagged proglucagon gene promoter have low expression of T1R1, T1R2, and T1R3, similar to the low expression on lingual taste buds (Reimann et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Of the numerous hormones released in response to luminal amino acids, the proglucagon-derived hormones glucagonlike peptide (GLP)-1 and GLP-2 secreted from enteroendocrine L cells are appealing as mediators of L-Glu/IMP-evoked HCO 3 Ϫ secretion: GLP-1 is released by oral glutamine in humans (Greenfield et al, 2009), whereas GLP-2 modulates neurally evoked anion secretion in the guinea pig intestine . A third possible hormone mediator is gastric inhibitory peptide/glucose-dependent insulinotropic peptide (GIP), released from K cells, which is released by luminal amino acids (O'Dorisio et al, 1976) and enhances duodenal HCO 3 Ϫ secretion (Flemström et al, 1982;Konturek et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

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Umami Receptor Activation Increases Duodenal Bicarbonate Secretion via Glucagon-Like Peptide-2 Release in Rats

Wang¹,

Inoue²,

Higashiyama³

et al. 2011

J Pharmacol Exp Ther

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Luminal nutrient chemosensing during meal ingestion is mediated by intestinal endocrine cells, which regulate secretion and motility via the release of gut hormones. We have reported that luminal coperfusion of L-Glu and IMP, common condiments providing the umami or proteinaceous taste, synergistically increases duodenal bicarbonate secretion (DBS) possibly via taste receptor heterodimers, taste receptor type 1, member 1 (T1R1)/R3. We hypothesized that glucose-dependent insulinotropic peptide (GIP) or glucagon-like peptide (GLP) is released by duodenal perfusion with L-Glu/IMP. We measured DBS with pH and CO 2 electrodes through a perfused rat duodenal loop in vivo. GIP, exendin (Ex)-4 (GLP-1 receptor agonist), or GLP-2 was intravenously infused (0.01-1 nmol/kg/h). L-Glu (10 mM) and IMP (0.1 mM) were luminally perfused with or without bolus intravenous injection (3 or 30 nmol/kg) of the receptor antagonists Pro 3 GIP, Ex-3(9-39), or GLP-2(3-33). GIP or GLP-2 infusion dose-dependently increased DBS, whereas Ex-4 infusion gradually decreased DBS. Luminal perfusion of L-Glu/IMP increased DBS, with no effect of Pro 3 GIP or Ex-3(9-39), whereas GLP-2(3-33) inhibited L-Glu/IMP-induced DBS. Vasoactive intestinal peptide (VIP)(6 -28) intravenously or N G -nitro-L-arginine methyl ester coperfusion inhibited the effect of L-Glu/IMP. Perfusion of L-Glu/IMP increased portal venous concentrations of GLP-2, followed by a delayed increase of GLP-1, with no effect on GIP release. GLP-1/2 and T1R1/R3 were expressed in duodenal endocrine-like cells. These results suggest that luminal L-Glu/IMPinduced DBS is mediated via GLP-2 release and receptor activation followed by VIP and nitric oxide release. Because GLP-1 is insulinotropic and GLP-2 is intestinotrophic, umami receptor activation may have additional benefits in glucose metabolism and duodenal mucosal protection and regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Umami Receptor Activation Increases Duodenal Bicarbonate Secretion via Glucagon-Like Peptide-2 Release in Rats

Wang¹,

Inoue²,

Higashiyama³

et al. 2011

J Pharmacol Exp Ther

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“…A total of 30 g (205 mmoles) was given orally to eight normal subjects, eight obese subjects, and eight obese subjects with impaired glucose tolerance (23). Insulin and glucagon increased significantly without a change in glucose concentra-tion in all subjects.…”

Section: Previous Literature On Orally Ingested Specific Amino Acidsmentioning

confidence: 99%

Amino acid ingestion and glucose metabolism—A review

2010

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SummaryInterest in the effect of proteins or amino acids on glucose metabolism dates back at least a century, largely because it was demonstrated that the amino acids from ingested protein could be converted into glucose. Indeed, these observations influenced the dietary information provided to people with diabetes. Subsequently it was shown that ingested protein did not raise the blood glucose concentration. It also was shown that proteins could stimulate a rise in insulin and glucagon but the response to various proteins was different. In addition, it was shown that individual amino acids also could stimulate a rise in insulin and in glucagon concentrations. When individual amino acids are ingested by normal subjects, there is an ordering of the insulin and glucagon responses. However, the order is not the same for insulin and glucagon. In addition, the metabolic response cannot be predicted based on the functional groups of the amino acids. Thus, empirical prediction of the metabolic response to ingested single amino acids is not possible. IUBMBIUBMB Life, 62(9): [660][661][662][663][664][665][666][667][668] 2010

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“…In contrast, oral and ID L-Gln (although administered in much larger doses of 15-30 g) elevated plasma glucagon-like peptide-1 (GLP-1) concentrations, in healthy, obese, and type 2 diabetic subjects. 19,29,30 Our observations suggest that the effect of amino acids on CCK secretion (at loads of up to 10 g) depends on the chemical characteristics of the amino acid. We have demonstrated recently that also L-Trp potently stimulates CCK secretion, 16 thus, aromatic amino acids appear to be potent CCK secretagogues.…”

Section: Discussionmentioning

confidence: 89%

Effects of Intraduodenal Infusions of L-phenylalanine and L-glutamine on Antropyloroduodenal Motility and Plasma Cholecystokinin in Healthy Men

Steinert

Landrock

Horowitz

et al. 2015

J Neurogastroenterol Motil

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Background/AimsDietary proteins have potent eating-inhibitory and glucose-lowering effects, which may be mediated via effects of amino acids on gastrointestinal hormone and motor function, although little information is available. We have now evaluated the effects of L-phenylalanine (L-Phe) and L-glutamine (L-Gln) on antropyloroduodenal motility and plasma cholecystokinin (CCK) concentrations. MethodsTwo double-blind, 3-way cross-over studies were performed, each including 10 healthy, normal-weight men. We determined the antropyloroduodenal motor and plasma CCK responses to 90-minute intraduodenal infusions of L-Phe (study A) or L-Gln (study B), each at 0.15 kcal/min (total 13.5 kcal), or 0.45 kcal/min (total 40.5 kcal), or saline (control), in randomized fashion. ResultsIntraduodenal L-Phe at 0.45 kcal/min, but not at 0.15 kcal/min, suppressed antral (P < 0.01), and stimulated phasic (P < 0.01), but not tonic, pyloric, or duodenal pressures, while L-Phe at both 0.15 kcal/min and 0.45 kcal/min stimulated plasma CCK. In contrast, L-Gln had no effect on antral, duodenal or pyloric pressures, or plasma CCK. Conclusions

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Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects

Abstract: Glutamine effectively increases circulating GLP-1, GIP, and insulin concentrations in vivo and may represent a novel therapeutic approach to stimulating insulin secretion in obesity and type 2 diabetes.

Cited by 208 publications

References 29 publications

Umami Receptor Activation Increases Duodenal Bicarbonate Secretion via Glucagon-Like Peptide-2 Release in Rats

Umami Receptor Activation Increases Duodenal Bicarbonate Secretion via Glucagon-Like Peptide-2 Release in Rats

Amino acid ingestion and glucose metabolism—A review

Effects of Intraduodenal Infusions of L-phenylalanine and L-glutamine on Antropyloroduodenal Motility and Plasma Cholecystokinin in Healthy Men

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