Regulation Of Gastric Emptying Research Articles

Gastrointestinal hormones and regulation of gastric emptying.

In this review, we evaluate recent findings related to the association between gastrointestinal hormones and regulation of gastric emptying. Motilin and ghrelin, which act during fasting, promote gastric motility, whereas most of the hormones secreted after a meal inhibit gastric motility. Serotonin has different progastric or antigastric motility effects depending on the receptor subtype. Serotonin receptor agonists have been used clinically to treat dyspepsia symptoms but other hormone receptor agonists or antagonists are still under development. Glucagon-like peptide 1 agonists, which have gastric motility and appetite-suppressing effects are used as a treatment for obesity and diabetes. Gastrointestinal hormones play an important role in the regulation of gastric motility. Various drugs have been developed to treat delayed gastric emptying by targeting gastrointestinal hormones or their receptors but few have been commercialized.

Emerging roles of bile acids in control of intestinal functions.

Bile acids and their signalling pathways are increasingly recognized as potential therapeutic targets for several diseases. This review summarizes new insights in bile acid physiology, focussing on regulatory roles of bile acids in intestinal functions. Recent studies have highlighted the interactions between bile acids and gut microbiome: interfering with microbiome composition may be beneficial in treatment of liver and metabolic diseases by modulating bile acid composition, as different bile acid species have different signalling functions. In the intestine, bile acid receptors FXR, VDR and TGR5 are involved in control of barrier function, paracellular ion transport and hormone release. Specific microbial bile acid metabolites modulate immune responses of the host. In addition, new functions of bile acids in regulation of gastric emptying and satiation via brain-gut-liver axis have been discovered. Identification of Cyp2c70 as the enzyme responsible for generation of hydrophilic mouse/rat-specific muricholic acids has allowed the generation of murine models with a human-like bile acid composition. Specific bile acids act as important signalling molecules affecting whole body metabolism, specific transport processes and immunity in different segments of the intestinal tract. Their relevance for human (patho)physiology is emerging. Novel mouse models with human-like bile acid composition will aid to accelerate translational research.

Should Workers Avoid Consumption of Chilled Fluids in a Hot and Humid Climate?

Despite provision of drinking water as the most common method of occupational heat stress prevention, there remains confusion in hydration messaging to workers. During work site interactions in a hot and humid climate, workers commonly report being informed to consume tepid fluids to accelerate rehydration. When questioned on the evidence supporting such advice, workers typically cite that fluid absorption is delayed by ingestion of chilled beverages. Presumably, delayed absorption would be a product of fluid delivery from the gut to the intestines, otherwise known as gastric emptying. Regulation of gastric emptying is multifactorial, with gastric volume and beverage energy density the primary factors. If gastric emptying is temperature dependent, the impact of cooling is modest in both magnitude and duration (≤ 5 minutes) due to the warming of fluids upon ingestion, particularly where workers have elevated core temperature. Given that chilled beverages are most preferred by workers, and result in greater consumption than warm fluids during and following physical activity, the resultant increased consumption of chilled fluids would promote gastric emptying through superior gastric volume. Hence, advising workers to avoid cool/cold fluids during rehydration appears to be a misinterpretation of the research. More appropriate messaging to workers would include the thermal benefits of cool/cold fluid consumption in hot and humid conditions, thereby promoting autonomy to trial chilled beverages and determine personal preference. In doing so, temperature-based palatability would be maximized and increase the likelihood of workers maintaining or restoring hydration status during and after their work shift.

Xiao chai hu tang for liver diseases: A literature review

The objective of this study is to summarize the pharmacological effects and the mechanisms of action of Xiao Chai Hu Tang (XCHT, Minor Bupleurum Decoction) on liver diseases, so as to give relevant researchers a valuable insight and benefit patients with hepatopathy. PubMed was used to search for and collect scientific publications related to XCHT and liver diseases from 1986 to 2016. The available scientific results or evidence were read, classified, and analyzed. XCHT showed clinical efficacy in patients with hepatic diseases including hepatitis, hepatic fibrosis, and hepatoma. The mechanisms involved the production of cytokines, the regulation of immune function, the suppression of lipid peroxidation, etc., XCHT might work on the metabolism of some medications such as tolbutamide by the regulation of gastric emptying and intragastric pH. XCHT exhibited a very low toxicity profile, such as interstitial pneumonia due to duration of medication, patients' age, and drug combination. XCHT has been a eutherapeutic supplemental remedy for liver diseases. However, many mechanisms of action and effects of XCHT on new types of liver diseases still remain unclear, so more and more animal experiments and human clinical trials are needed to obtain enough proofs for the clinical use of XCHT in new types of hepatosis such as nonalcoholic fatty liver disease and autoimmune liver disease.

Effects of inhomogeneity on triglyceride digestion of emulsions using an in vitro digestion model (Tiny TIM).

The colloidal behaviour and extent of lipolysis of various emulsions stabilized by whey protein and Tween were studied using the TNO Intestinal Model (TIM) extended with a purposely designed gastric compartment. The in vitro results suggest that creaming of a fatty layer in the gastric region causes a delay in fat entering the small intestinal region, delays and reduces the free fatty acid content in the small intestinal lumen and delays fat absorption. It was shown that controlling the pH with pig gastric juice instead of simulated gastric juice delayed creaming of the emulsions significantly, which resulted in faster gastric lipolysis. However, because the digestive conditions are not adjusted by physiological regulation mechanisms such as the regulation of gastric emptying by the detection of nutrients in the small intestine, care must be taken to translate these results to the in vivo reality. It is expected that the differences between the systems will be tempered by the physiological feedback regulation mechanisms of digestion.

The role of glucagon-like peptide-1 impairment in obesity and potential therapeutic implications

The hormone glucagon-like peptide-1 (GLP-1) is released from the gut in response to food intake. It acts as a satiety signal, leading to reduced food intake, and also as a regulator of gastric emptying. Furthermore, GLP-1 functions as an incretin hormone, stimulating insulin release and inhibiting glucagon secretion from the pancreas in response to food ingestion. Evidence suggests that the action or effect of GLP-1 may be impaired in obese subjects, even in those with normal glucose tolerance. GLP-1 impairment may help explain the increased gastric emptying and decreased satiety signalling seen in obesity. Incretin impairment, probably associated with reduced insulinotropic potency of GLP-1, is also characteristic of type 2 diabetes (T2D). Therefore, it is possible that incretin impairment may contribute to the pathophysiological bridge between obesity and T2D. This review summarises current knowledge about the pathophysiology and consequences of GLP-1 and incretin impairment in obesity, and examines the evidence for an incretin-related link between obesity and T2D. It also considers the current literature surrounding the novel use of GLP-1 receptor agonists as a treatment for obesity in patients with normoglycaemia, prediabetes and T2D.

NMDA Receptors of Gastric-Projecting Neurons in the Dorsal Motor Nucleus of the Vagus Mediate the Regulation of Gastric Emptying by EA at Weishu (BL21)

A large number of studies have been conducted to explore the efficacy of electroacupuncture (EA) for the treatment of gastrointestinal motility. While several lines of evidence addressed the basic mechanism of EA on gastrointestinal motility regarding effects of limb and abdomen points, the mechanism for effects of the back points on gastric motility still remains unclear. Here we report that the NMDA receptor (NMDAR) antagonist kynurenic acid inhibited the gastric emptying increase induced by high-intensity EA at BL21 and agonist NMDA enhanced the effect of the same treatment. EA at BL21 enhanced NMDAR, but not AMPA receptor (AMPAR) component of miniature excitatory postsynaptic current (mEPSC) in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). In sum, our data demonstrate an important role of NMDAR-mediated synaptic transmission of gastric-projecting DMV neurons in mediating EA at BL21-induced enhancement of gastric emptying.

The possible involvement of dopamine D 3 receptors in the regulation of gastric emptying in rats

Aim The inhibitory effect of dopamine on gastric motility is thought to be mediated via a decrease in acetylcholine release resulting from stimulation of enteric neuronal dopamine D 2 receptors. The aim of this study was to investigate the possible involvement of the dopamine D 3 receptor in the regulation of gastric motility in rats using selective dopamine D 3 receptor agonists or a dopamine D 3 receptor antagonist. Main methods Gastric emptying was assessed using the phenol red method after rats were treated with varying doses of dopamine D 3 receptor agonists or a dopamine D 3 receptor antagonist. Key findings S(+)-PD 128,907 (0.01–1 mg/kg, s.c.), a selective dopamine D 3 receptor agonist, dose-dependently delayed gastric emptying in rats. Other dopamine D 3 receptor agonists (i.e., R(+)-7-OH-DPAT [0.03–1 mg/kg, s.c.] and quinpirole [0.01–1 mg/kg, s.c.]) also delayed gastric emptying in rats. Both the selective dopamine D 1 and D 5 receptor agonist SKF-38393 and the selective dopamine D 4 receptor agonist PD 168,077 failed to delay gastric emptying in rats. The selective dopamine D 3 receptor antagonist (+)-S 14297 (10 mg/kg, s.c.) partially inhibited the S(+)-PD 128,907-induced delay in gastric emptying. Although an administration of S(+)-PD 128,907 (1–100 μg/kg) into the 4th cerebral ventricle partially and dose-dependently delayed gastric emptying in rats, its administration into the lateral cerebral ventricle did not affect gastric emptying. Significance The results presented here suggest that peripheral dopamine D 2 receptors and, at least in part, dopamine D 3 and central dopamine D 2/D 3 receptors play an important role in the regulation of gastric motility in rats.

Gastric emptying of hexose sugars: role of osmolality, molecular structure and the CCK1 receptor

It is widely reported that hexose sugars slow gastric emptying (GE) via osmoreceptor stimulation but this remains uncertain. We evaluated the effects of a panel of hexoses of differing molecular structure, assessing the effects of osmolality, intra-individual reproducibility and the role of the CCK(1) receptor, in the regulation of GE by hexoses. Thirty one healthy non-obese male and female subjects were studied in a series of protocols, using a (13) C-acetate breath test to evaluate GE of varying concentrations of glucose, galactose, fructose and tagatose, with water, NaCl and lactulose as controls. GE was further evaluated following the administration of a CCK(1) receptor antagonist. Three subjects underwent repeated studies to evaluate intra-individual reproducibility. At 250 mOsmol, a hexose-specific effect was apparent: tagatose slowed GE more potently than water, glucose and fructose (P < 0.05). Fructose (P < 0.05) also slowed GE, but with substantial inter-, but not intra-, individual differences. As osmolality increased further the hexose-specific differences were lost. At 500 mOsmol, all hexoses slowed GE compared with water (P < 0.05), whereas lactulose and saline did not. The slowing of GE by hexose sugars appeared to be CCK(1) receptor-dependent. The effects of hexose sugars on GE appear related to their molecular structure rather than osmolality per se, and are, at least in part, CCK(1) receptor-dependent.

PTH-042 Endogenous cholecystokinin in the regulation of gastric emptying in lean and obese humans

Introduction Cholecystokinin (CCK), a gut peptide released postprandially from the small intestine, has been shown to reduce food intake and slow gastric emptying (GE) in man. Resistance to gut peptides involved in energy homeostasis such as leptin has also been demonstrated in obese individuals. Similarly, a reduction in sensitivity to CCK may lead to increased food intake and ultimately affect body weight. It is not known if the effects of CCK are consistent between obese and lean individuals. The aim of this study was to determine the effect of the CCK1 receptor antagonist, dexloxiglumide, on GE of a nutrient releasing meal, in lean and obese subjects. Methods Ten obese (BMI; 47 kg/m2 ±7) and 10 non-obese (BMI; 22 kg/m2 ±2) participants ingested the CCK1 receptor antagonist, dexloxiglumide, or placebo. An hour later, 500 ml of skimmed milk containing 13C-acetate was consumed. A 13C-acetate breath test was used as a proxy measure for the rate of GE. Results GE of skimmed milk was slower in obese subjects when compared to lean subjects in both placebo (p=0.013) and dexloxiglumide conditions (p=0.017). When compared to placebo, dexloxiglumide accelerated GE of skimmed milk in both lean (p=0.034) and obese subjects (p=0.022), however, the percentage increase in GE rate with dexloxiglumide vs placebo was greater in obese compared to the lean subjects (p=0.017). There was a direct relationship between the rate of GE and BMI in both placebo (p=0.00), and dexloxiglumide conditions (p=0.04). Conclusion These results demonstrate that the response to dexloxiglumide does not appear to be reduced, but rather increased in obese subjects, suggesting that sensitivity to CCK is not impaired in obesity. These results also suggest an overall slower rate of GE in obese compared to lean subjects, which could be a contributing factor in the pathogenesis of obesity.

Effects of Proton Pump Inhibitors on Gastric Emptying: A Systematic Review

The proton pump inhibitor (PPI) is widely used for the treatment of gastroesophageal reflux disease, peptic ulcer diseases, and functional dyspepsia. The pathogenesis of these acid-related and/or functional upper gastrointestinal disorders is potentially associated with abnormal gastric emptying. To date, variable effects of PPIs on gastric emptying have been reported. Therefore, it is relevant to gather and analyze published information on this topic. A systematic literature search has been performed, showing that the delaying effect of PPIs on gastric emptying of solid meals is consistent, whereas the effect of PPIs on the emptying of liquids is inconsistent. The underlying mechanisms whereby PPIs may affect gastric emptying have been discussed, most of which still remain hypothetic. Gastric emptying of solids involves a process of peptic hydrolysis. PPIs impair the hydrolytic digestion by inhibiting acid-dependent peptic activity, thereby delaying the solid emptying. Gastric emptying of liquids largely depends on volume and energy density of intragastric contents. PPIs variably modify the volume and the energy density by reducing gastric fluid secretion, thereby modifying the liquid emptying in an unpredictable manner. Hypergastrinemia has been considered to delay gastric emptying, but it seems of minor importance in the regulation of gastric emptying during PPI use. The delayed emptying of solids due to PPI therapy may have clinical implications in the management of gastroesophageal reflux disease, functional dyspepsia, as well as diabetes.

On the role of glucose-dependent insulintropic polypeptide in postprandial metabolism in humans

We investigated the role of glucose-dependent insulintropic polypeptide (GIP) in the regulation of gastric emptying (GE), appetite, energy intake (EI), energy expenditure (EE), plasma levels of triglycerides (TAG), and free fatty acids (FFA) in humans. First, 20 healthy males received intravenous infusion of GIP (0.8 pmol.kg(-1).min(-1)) or saline for 300 min during and after a fixed meal (protocol 1). GE was measured using paracetamol, appetite sensations using visual analog scales, EE using indirect calorimetry, and EI during a subsequent ad libitum meal (at 300 min). Next, 10 healthy males received intravenous infusions of Intralipid, glucose, or Intralipid plus glucose, with and without GIP (1.5 pmol.kg(-1).min(-1)) for 300 min (protocol 2). In protocol 1, GIP did not have any effect on GE, EI, EE, removal of TAG, or FFA and did not influence the subjective feeling of hunger, satiety, fullness or prospective food consumption compared with saline. In protocol 2, no difference was seen in the plasma TAG on Intralipid + GIP/saline and Intralipid + glucose + GIP/saline days. FFA concentrations were lower on Intralipid + glucose + GIP/saline days (P < 0.05) compared with Intralipid + GIP/saline days and on Intralipid + GIP day (P < 0.004) compared with Intralipid + saline day. Insulin increased on all GIP days compared with saline days (P < 0.05). In conclusion, while confirming its insulinotropic effects, these data suggest that GIP does not affect GE, appetite, energy intake, EE, or the clearance rate of the applied TAG formulation in humans. However, both insulin and GIP lower post-Intralipid FFA concentration, GIP probably via stimulation of insulin secretion, increasing FFA reesterification.

Endogenous Glucagon-Like Peptide-1 Slows Gastric Emptying in Healthy Subjects, Attenuating Postprandial Glycemia

The role of glucagon-like peptide-1 (GLP-1) in the regulation of gastric emptying is uncertain. The aim of this study was to determine the effects of endogenous GLP-1 on gastric emptying, glucose absorption, and glycemia in health. Ten healthy fasted subjects (eight males, two females; 48 +/- 7 yr) received the specific GLP-1 antagonist, exendin(9-39) amide [ex(9-39)NH(2)] (300 pmol/kg x min iv), or placebo, between -30 and 180 min in a randomized, double-blind, crossover fashion. At 0 min, a mashed potato meal ( approximately 2600 kJ) containing 3 g 3-ortho-methyl-D-glucose (3-OMG) and labeled with 20 MBq (99m)Technetium-sulphur colloid was eaten. Gastric emptying, including the time taken for 50% of the meal to empty from the stomach (T50), blood glucose, plasma 3-OMG, and plasma insulin were measured. Ex(9-39)NH(2) accelerated gastric emptying [T50 ex(9-39)NH(2), 68 +/- 8 min, vs. placebo, 83 +/- 7 min; P < 0.001] and increased the overall glycemic response to the meal [area under the curve (0-180 min) ex(9-39)NH(2), 1540 +/- 106 mmol/liter x min, vs. placebo, 1388 +/- 90 mmol/liter x min; P < 0.02]. At 60 min, ex(9-39)NH(2) increased the rise in glycemia [ex(9-39)NH(2), 9.9 +/- 0.5 mmol/liter, vs. placebo, 8.4 +/- 0.5 mmol/liter; P < 0.01], plasma 3-OMG [ex(9-39)NH(2), 0.25 +/- 0.01 mmol/liter, vs. placebo, 0.21 +/- 0.01 mmol/liter; P < 0.05], and plasma insulin [ex(9-39)NH(2), 82 +/- 13 mU/liter, vs. placebo, 59 +/- 9 mU/liter; P < 0.05] concentrations. There was a close within-subject correlation between glycemia and gastric emptying [e.g. at 60 min, the increment in blood glucose and gastric emptying (T50); r = -0.89; P < 0.001]. GLP-1 plays a physiological role to slow gastric emptying in health, which impacts on glucose absorption and, hence, postprandial glycemia.

Role of intestinal “taste” receptors in the regulation of gastric emptying in humans

Role of intestinal “taste” receptors in the regulation of gastric emptying in humans

Effects of Euglycemic Hyperinsulinemia and Lipid Infusion on Circulating Cholecystokinin

Functions of the gut hormone cholecystokinin (CCK) include an important role in the regulation of gastric emptying, postprandial glucose homeostasis, and postmeal satiety. Postprandial CCK responses are significantly blunted in type 2 diabetic patients by unknown mechanisms. We hypothesized that hyperinsulinemia and lipid infusion influence circulating levels of biologically active CCK. Eleven healthy subjects were studied in a cross-over design after 10-h overnight fasts, using euglycemic-hyperinsulinemic clamps for 443 min, with an additional infusion of lipid-heparin (1.25 ml.min(-1)) or saline (1.25 ml.min(-1)) for the last 300 min after constant plasma glucose levels were achieved. Euglycemic-hyperinsulinemia resulted in a sustained, up to 5-fold increase of plasma CCK (P < 0.001). When adding lipid infusion instead of saline, CCK concentrations rapidly declined and returned to baseline levels (CCK(300 min) 1.1 +/- 0.2 vs. 3.3 +/- 0.3 pmol/liter, P < 0.001). Partial intraclass correlation showed an independent correlation of plasma CCK with free fatty acids (r(ic) = -0.377, P < 0.001) but not with serum insulin (r(ic) = 0.077, P = 0.32). Whole-body insulin sensitivity decreased in lipid-exposed subjects (M value 7.1 +/- 0.7 vs. 5.6 +/- 0.9 mg.kg.min(-1), P = 0.017) but was not independently correlated with CCK (r(ic) = 0.040, P = 0.61). We report novel findings showing that circulating CCK markedly increased in the euglycemic-hyperinsulinemic state, possibly as a result of near-complete suppression of circulating free fatty acids. Moreover, raising blood lipids even moderately by lipid infusion rapidly and significantly interfered with this effect, suggesting that a negative feedback mechanism of blood lipids on circulating CCK might exist.

The role of endocannabinoids in the regulation of gastric emptying: alterations in mice fed a high‐fat diet

Endocannabinoids (via cannabinoid CB(1) receptor activation) are physiological regulators of intestinal motility and food intake. However, their role in the regulation of gastric emptying is largely unexplored. The purpose of the present study was to investigate the involvement of the endocannabinoid system in the regulation of gastric emptying in mice fed either a standard diet (STD) or a high-fat diet (HFD) for 14 weeks. Gastric emptying was evaluated by measuring the amount of phenol red recovered in the stomach after oral challenge; CB(1) expression was analysed by quantitative reverse transcription-PCR; endocannabinoid (anandamide and 2-arachidonoyl glycerol) levels were measured by liquid chromatography-mass spectrometry. Gastric emptying was reduced by anandamide, an effect counteracted by the CB(1) receptor antagonist rimonabant, but not by the CB(2) receptor antagonist SR144528 or by the transient receptor potential vanilloid type 1 (TRPV1) antagonist 5'-iodoresiniferatoxin. The fatty acid amide hydrolase (FAAH) inhibitor N-arachidonoyl-5-hydroxytryptamine (but not the anandamide uptake inhibitor OMDM-2) reduced gastric emptying in a way partly reduced by rimonabant. Compared to STD mice, HFD mice exhibited significantly higher body weight and fasting glucose levels, delayed gastric emptying and lower anandamide and CB(1) mRNA levels. N-arachidonoylserotonin (but not rimonabant) affected gastric emptying more efficaciously in HFD than STD mice. Gastric emptying is physiologically regulated by the endocannabinoid system, which is downregulated following a HFD leading to overweight.

The relationship between gastric emptying, plasma cholecystokinin, and peptide YY in critically ill patients

BackgroundCholecystokinin (CCK) and peptide YY (PYY) are released in response to intestinal nutrients and play an important physiological role in regulation of gastric emptying (GE). Plasma CCK and PYY concentrations are elevated in critically ill patients, particularly in those with a history of feed intolerance. This study aimed to evaluate the relationship between CCK and PYY concentrations and GE in critical illness.MethodsGE of 100 mL of Ensure® meal (106 kcal, 21% fat) was measured using a 13C-octanoate breath test in 39 mechanically ventilated, critically ill patients (24 males; 55.8 ± 2.7 years old). Breath samples for 13CO2 levels were collected over the course of 4 hours, and the GE coefficient (GEC) (normal = 3.2 to 3.8) was calculated. Measurements of plasma CCK, PYY, and glucose concentrations were obtained immediately before and at 60 and 120 minutes after administration of Ensure.ResultsGE was delayed in 64% (25/39) of the patients. Baseline plasma CCK (8.5 ± 1.0 versus 6.1 ± 0.4 pmol/L; P = 0.045) and PYY (22.8 ± 2.2 versus 15.6 ± 1.3 pmol/L; P = 0.03) concentrations were higher in patients with delayed GE and were inversely correlated with GEC (CCK: r = -0.33, P = 0.04, and PYY: r = -0.36, P = 0.02). After gastric Ensure, while both plasma CCK (P = 0.03) and PYY (P = 0.02) concentrations were higher in patients with delayed GE, there was a direct relationship between the rise in plasma CCK (r = 0.40, P = 0.01) and PYY (r = 0.42, P < 0.01) from baseline at 60 minutes after the meal and the GEC.ConclusionIn critical illness, there is a complex interaction between plasma CCK, PYY, and GE. Whilst plasma CCK and PYY correlated moderately with impaired GE, the pathogenetic role of these gut hormones in delayed GE requires further evaluation with specific antagonists.

Effect of peripheral obestatin on gastric emptying and intestinal contractility in rodents

Obestatin has recently been discovered in the rat stomach. It is encoded by the ghrelin gene and has been claimed to be a functional opponent of ghrelin and to be the natural ligand of the GPR39 receptor. The latter could not be confirmed by Holst et al. (Endocrinology, 2006). Yet, in GPR39 knockout mice, gastric emptying is accelerated. We verified the effects of obestatin on gastric emptying and intestinal contractility in rodents. Gastric emptying was measured with the (14)C octanoic breath test in mice. In vitro, the effect of obestatin was studied on electrically stimulated and non-stimulated strips from the fundus and small intestine of mice and rats. Obestatin (60, 125, 250 nmol kg(-1)) did not affect gastric emptying parameters (T(half) and T(lag)) and did not inhibit the prokinetic effects of ghrelin. Mouse and rat intestinal and fundic smooth muscle strips did not respond to obestatin either in the absence or in the presence of electrical field stimulation. Obestatin (125 nmol kg(-1)) did not inhibit fasting-induced hyperphagia. Our results suggest that peripheral obestatin is not a satiety signal that plays a role in the regulation of gastric emptying and do not support the concept that obestatin is a physiological opponent of ghrelin.

A Role for Pancreatic Polypeptide in the Regulation of Gastric Emptying and Short-Term Metabolic Control

Previous studies using pancreatic polypeptide (PP) infusions in humans have failed to show an effect on gastric emptying, glucose metabolism, and insulin secretion. This might be due to the use of nonhuman sequences of the peptide. The objective of this study was to use synthetic human PP to study gastric emptying rates of a solid meal and postprandial hormone secretion and glucose disposal as well as the gastric emptying rate of water. This was a single-blind study. The study was performed at a university hospital. Fourteen healthy adult subjects were studied. Infusion of saline or PP at 0.75 or 2.25 pmol/kg.min was given to eight subjects (gastric emptying of solid food), and infusion of saline or PP at 2.25 pmol/kg.min was given to six subjects (gastric emptying of water). The main outcome measures were gastric emptying of solids (scintigraphy), hunger ratings (visual analog scale), and plasma concentrations of PP, insulin, glucagon, somatostatin, glucagon-like peptide 1, glucose, and gastric emptying of plain water (scintigraphy). PP prolonged the lag phase and the half-time of emptying of the solid meal. The change in hunger rating, satiety, desire to eat after the meal, or prospective consumption was not affected. The postprandial rise in plasma glucose was prolonged by PP. The postprandial rise in insulin was also delayed by PP. PP had no significant effect on the emptying of water. PP inhibits gastric emptying of solid food and delays the postprandial rise in plasma glucose and insulin. PP is suggested to have a physiological role in the pancreatic postprandial counterregulation of gastric emptying and insulin secretion.

Simultaneous determination of incretin hormones and their truncated forms from human plasma by immunoprecipitation and liquid chromatography–mass spectrometry

The incretins, glucose-dependent insulinotropic peptide (GIP 1–42) and glucagon-like peptide 1 (GLP-1 7–36), are involved in regulation of gastric emptying, glucose homeostasis, body fat regulation and the glucose-induced insulin secretion from the endocrine pancreas. After release in the circulation both peptides are rapidly degraded by the exopeptidase dipeptidyl peptidase IV (DP IV) to the inactive polypeptides GIP 3–42 and GLP-1 9–36. In vivo stabilization of the active incretins by orally available DP IV-inhibitors is now widely accepted as a new therapeutic approach in antidiabetic treatment. In order to demonstrate the pharmacodynamic effect of DP IV-inhibitors, it is necessary to measure the plasma levels of active and inactive forms of GIP and GLP-1. We previously described an immunoprecipitation method as sample preparation and concentration in combination with a LC–MS analysis for determination of active and inactive GIP. We could improve the efficiency and suitability of this method by reduction of the necessary sample volume to 1.0 ml and simultaneous measurement of GIP 1–42, GIP 3–42 and GLP-1 7–36, GLP-1 9–36, without loss of sensitivity. An LOQ of approximately 5 and 11 pmol/l was maintained for GIP and GLP-1, respectively.