Xenin plasma concentrations during modified sham feeding and during meals of different composition demonstrated by radioimmunoassay and chromatography

Feurle, Gerhard E.; Sotirios, Ikonomu; Partoulas, G.; Stoschus, Bodo; Hamscher, Gerd

doi:10.1016/s0167-0115(02)00281-1

Cited by 31 publications

(22 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since its discovery in 1992, xenin has received attention as an effecter of gut motility (Feurle et al 1992(Feurle et al , 2003. In addition, xenin is now thought to be involved in the regulation of calorie intake (Leckstrom et al 2009) and possibly insulin secretion (Silvestre et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…xenin injection has been shown to reduce food intake in mice (Leckstrom et al 2009). Similar to other anorectic gastrointestinal peptides, levels of circulating xenin appear to increase after a meal, suggesting that xenin may regulate food intake by acting as a satiety factor (Feurle et al 2003). In addition, Cooke et al (2009) demonstrated that i.c.v.…”

Section: Introductionmentioning

confidence: 94%

“…Interestingly, a C-terminally truncated form of xenin, xenin-8, has been shown to exert possible insulinotropic and glucagonotropic actions in the perfused rat pancreas, but lacked somatostatin-releasing effects (Silvestre et al 2003). Furthermore, given that plasma xenin concentrations were significantly elevated during feeding (Feurle et al 2003), and that it is secreted from the same K cell as the incretin hormone glucose-dependent insulinotropic polypeptide (GIP), the possibility of xenin functioning in an incretin-like context is also conceivable. Therefore, the present study has examined the plasma stability and satiety effects of xenin, and further characterised the glucoselowering and insulinotropic effects of xenin both alongside GIP, glucagon-like peptide-1 (GLP1) and neurotensin.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of the degradation and metabolic effects of the gut peptide xenin on insulin secretion, glycaemic control and satiety

Taylor

Irwin²,

McKillop³

et al. 2010

Journal of Endocrinology

View full text Add to dashboard Cite

Recently, glucagon-like peptide 1 (GLP1) and glucosedependent insulinotropic polypeptide (GIP) have received much attention regarding possible roles in aetiology and treatment of type 2 diabetes. However, peptides co-secreted from the same enteroendocrine cells are less well studied. The present investigation was designed to characterise the in vitro and in vivo effects of xenin, a peptide co-secreted with GIP from intestinal K-cells. We examined the enzymatic stability, insulin-releasing activity and associated cAMP production capability of xenin in vitro. In addition, the effects of xenin on satiety, glucose homoeostasis and insulin secretion were examined in vivo. Xenin was time dependently degraded (t 1/2 Z162G6 min) in plasma in vitro. In clonal BRIN-BD11 cells, xenin stimulated insulin secretion at 5 . 6 mM (P!0 . 05) and 16 . 7 mM (P!0 . 05 to P!0 . 001) glucose levels compared to respective controls. Xenin also exerted an additive effect on GIP, GLP1 and neurotensin-mediated insulin secretion. In clonal b-cells, xenin did not stimulate cellular cAMP production, alter membrane potential or elevate intra-cellular Ca 2C. In normal mice, xenin exhibited a short-acting (P!0 . 01) satiety effect at high dosage (500 nmol/kg). In overnight fasted mice, acute injection of xenin enhanced glucose-lowering and elevated insulin secretion when injected concomitantly or 30 min before glucose. These effects were not observed when xenin was administered 60 min before the glucose challenge, reflecting the short half-life of the native peptide in vivo. Overall, these data demonstrate that xenin may have significant metabolic effects on glucose control, which merit further study.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of the degradation and metabolic effects of the gut peptide xenin on insulin secretion, glycaemic control and satiety

Taylor

Irwin²,

McKillop³

et al. 2010

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Supraphysiologic concentrations of xenin increased glucose-stimulated insulin release in perfused rat pancreas (45). In contrast to GIP, xenin is also released in response to sham feeding (72). Clearly, the physiologic importance for xenin has not been established.…”

Section: Discussionmentioning

confidence: 99%

Targeted Ablation of Glucose-dependent Insulinotropic Polypeptide-producing Cells in Transgenic Mice Reduces Obesity and Insulin Resistance Induced by a High Fat Diet

Althage

Ford

Wang

et al. 2008

Journal of Biological Chemistry

163

125

View full text Add to dashboard Cite

The K cell is a specific sub-type of enteroendocrine cell located in the proximal small intestine that produces glucosedependent insulinotropic polypeptide (GIP), xenin, and potentially other unknown hormones. Because GIP promotes weight gain and insulin resistance, reducing hormone release from K cells could lead to weight loss and increased insulin sensitivity. However, the consequences of coordinately reducing circulating levels of all K cell-derived hormones are unknown. To reduce the number of functioning K cells, regulatory elements from the rat GIP promoter/gene were used to express an attenuated diphtheria toxin A chain in transgenic mice. K cell number, GIP transcripts, and plasma GIP levels were profoundly reduced in the GIP/DT transgenic mice. Other enteroendocrine cell types were not ablated. Food intake, body weight, and blood glucose levels in response to insulin or intraperitoneal glucose were similar in control and GIP/DT mice fed standard chow. In contrast to single or double incretin receptor knock-out mice, the incretin response was absent in GIP/DT animals suggesting K cells produce GIP plus an additional incretin hormone. Following high fat feeding for 21-35 weeks, the incretin response was partially restored in GIP/DT mice. Transgenic versus wildtype mice demonstrated significantly reduced body weight (25%), plasma leptin levels (77%), and daily food intake (16%) plus enhanced energy expenditure (10%) and insulin sensitivity. Regardless of diet, long term glucose homeostasis was not grossly perturbed in the transgenic animals. In conclusion, studies using GIP/DT mice demonstrate an important role for K cells in the regulation of body weight and insulin sensitivity. Enteroendocrine (EE)2 cells are a complex population of rare, diffusely distributed hormone-producing intestinal epithelial cells (1-3). Peptides and hormones secreted by EE cells play important roles in many aspects of gastrointestinal and whole animal physiology (4 -6). There are at least 16 different subtypes of EE cells based upon the major product(s) synthesized and secreted by individual cells (1). Several EE cell products, including GIP, glucagon-like peptide-1 (GLP-1), ghrelin, cholecystokinin, and peptide tyrosine, regulate food intake and/or degree of adiposity (7-11).GIP is produced almost exclusively by K cells located in the proximal small intestine and is secreted immediately after ingestion of a meal (4, 5, 12, 13). GIP release is regulated by nutrients in the intestinal lumen but not by those in the blood (4,6,13,14). Glucose (12,15,16), protein hydrolysates (17), specific amino acids (18), and fat (19) are major GIP secretagogues. Long term administration of a high fat diet increases intestinal GIP mRNA and peptide levels (12), as well as the circulating amount of plasma GIP (20, 21). There is a large body of biochemical and animal data suggesting that GIP signaling promotes the accumulation of fat (22-31). Obese humans also hyper-secrete GIP (32-36) suggesting that GIP may promote obesity in humans.Originally, G...

show abstract

“…Xenin-25 has also been found in many other tissues but only after treatment with pepsin indicating that these additional tissues probably do not produce significant levels of mature xenin-25 (20). It was also reported that xenin-25 is secreted in response to meal ingestion and sham feeding in humans (21). The response to sham feeding suggests that xenin-25 could prime the ␤-cell in preparation for the impending increase in circulating GIP and glucose levels that will occur after meal ingestion.…”

mentioning

confidence: 98%

Xenin-25 Potentiates Glucose-dependent Insulinotropic Polypeptide Action via a Novel Cholinergic Relay Mechanism

Wice

Wang

Crimmins

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

The intestinal peptides GLP-1 and GIP potentiate glucosemediated insulin release. Agents that increase GLP-1 action are effective therapies in type 2 diabetes mellitus (T2DM). However, GIP action is blunted in T2DM, and GIP-based therapies have not been developed. Thus, it is important to increase our understanding of the mechanisms of GIP action. We developed mice lacking GIP-producing K cells. Like humans with T2DM, "GIP/DT" animals exhibited a normal insulin secretory response to exogenous GLP-1 but a blunted response to GIP. Pharmacologic doses of xenin-25, another peptide produced by K cells, restored the GIP-mediated insulin secretory response and reduced hyperglycemia in GIP/DT mice. Xenin-25 alone had no effect. Studies with islets, insulin-producing cell lines, and perfused pancreata indicated xenin-25 does not enhance GIP-mediated insulin release by acting directly on the ␤-cell. The in vivo effects of xenin-25 to potentiate insulin release were inhibited by atropine sulfate and atropine methyl bromide but not by hexamethonium. Consistent with this, carbachol potentiated GIP-mediated insulin release from in situ perfused pancreata of GIP/DT mice. In vivo, xenin-25 did not activate c-fos expression in the hind brain or paraventricular nucleus of the hypothalamus indicating that central nervous system activation is not required. These data suggest that xenin-25 potentiates GIP-mediated insulin release by activating non-ganglionic cholinergic neurons that innervate the islets, presumably part of an enteric-neuronal-pancreatic pathway. Xenin-25, or molecules that increase acetylcholine receptor signaling in ␤-cells, may represent a novel approach to overcome GIP resistance and therefore treat humans with T2DM.The entero-insulin axis is a physiologic system composed of peptides secreted from the gastrointestinal tract that play an important role in regulating insulin secretion from pancreatic islet ␤-cells (1, 2). To date, attention has focused on two intestinal peptides, glucagon-like peptide-1 (GLP-1) 2 and glucosedependent insulinotropic polypeptide (GIP). GIP is produced predominantly by intestinal K cells located in the proximal small intestine, whereas GLP-1 is produced primarily by intestinal L-cells present in the distal bowel (3-5). Release of GLP-1 and GIP is controlled by nutrient levels in the lumen of the gut rather than the bloodstream. Both hormones are released into the bloodstream immediately after ingestion of a meal and then potentiate glucose-stimulated insulin release. This increase in insulin secretion has been termed the incretin effect. Importantly, the incretin effect occurs only in the presence of elevated blood glucose and does not cause postprandial hypoglycemia.An increase in circulating GLP-1 activity has significant therapeutic benefit in patients with T2DM (1, 2, 6 -10). Two major classes of drugs that accomplish this goal have recently been introduced into the market with substantial success. Long acting analogs of GLP-1 potentiate glucose-stimulated insulin secretion leadin...

show abstract

Xenin plasma concentrations during modified sham feeding and during meals of different composition demonstrated by radioimmunoassay and chromatography

Cited by 31 publications

References 19 publications

Evaluation of the degradation and metabolic effects of the gut peptide xenin on insulin secretion, glycaemic control and satiety

Evaluation of the degradation and metabolic effects of the gut peptide xenin on insulin secretion, glycaemic control and satiety

Targeted Ablation of Glucose-dependent Insulinotropic Polypeptide-producing Cells in Transgenic Mice Reduces Obesity and Insulin Resistance Induced by a High Fat Diet

Xenin-25 Potentiates Glucose-dependent Insulinotropic Polypeptide Action via a Novel Cholinergic Relay Mechanism

Contact Info

Product

Resources

About