Novel antidiabetic nutrients identified by in vivo screening for gastric secretion and emptying regulation in rats

Jordi, Josua; Herzog, Brigitte; Lutz, Thomas; Verrey, François

doi:10.1152/ajpregu.00273.2014

Cited by 6 publications

(6 citation statements)

References 42 publications

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“…A few studies in both humans and experimental animals have reported that gastric emptying of tryptophan, administered intragastrically or orally, is slowed compared with control, and in a dose-dependent fashion [ 13 , 14 , 32 ]. Moreover, we have shown that tryptophan, administered intraduodenally, potently stimulates pyloric pressures [ 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Intragastric Administration of Tryptophan on the Blood Glucose Response to a Nutrient Drink and Energy Intake, in Lean and Obese Men

et al. 2018

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Tryptophan stimulates plasma cholecystokinin and pyloric pressures, both of which slow gastric emptying. Gastric emptying regulates postprandial blood glucose. Tryptophan has been reported to decrease energy intake. We investigated the effects of intragastric tryptophan on the glycaemic response to, and gastric emptying of, a mixed-nutrient drink, and subsequent energy intake. Lean and obese participants (n = 16 each) received intragastric infusions of 1.5 g (“Trp-1.5g”) or 3.0 g (“Trp-3.0g”) tryptophan, or control, and 15 min later consumed a mixed-nutrient drink (56 g carbohydrates). Gastric emptying (13C-acetate breath-test), blood glucose, plasma C-peptide, glucagon, cholecystokinin and tryptophan concentrations were measured (t = 0–60 min). Energy intake was assessed between t = 60–90 min. In lean individuals, Trp-3.0g, but not Trp-1.5g, slowed gastric emptying, reduced C-peptideAUC and increased glucagonAUC (all P < 0.05), but did not significantly decrease the blood glucose response to the drink, stimulate cholecystokinin or reduce mean energy intake, compared with control. In obese individuals, Trp-3.0g, but not Trp-1.5g, tended to slow gastric emptying (P = 0.091), did not affect C-peptideAUC, increased glucagonAUC (P < 0.001) and lowered blood glucose at t = 30 min (P < 0.05), and did not affect cholecystokinin or mean energy intake. In obese individuals, intragastrically administered tryptophan may reduce postprandial blood glucose by slowing gastric emptying; the lack of effect on mean energy intake requires further investigation.

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Section: Discussionmentioning

confidence: 99%

Effects of Intragastric Administration of Tryptophan on the Blood Glucose Response to a Nutrient Drink and Energy Intake, in Lean and Obese Men

et al. 2018

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“…Technically, even more demanding than measuring food intake is the quantification of nutrient digestion, as there is no direct optical access to the gastrointestinal tract in most species. More specialized technologies, such as bioluminescence, MRI, or computed tomography, have been valuable to generate insights into in vivo dynamics of digestive function (10,18,19,31). However, all of these methods require immobilization of the experimental subject to reduce motion artifacts, thereby making concurrent behavioral observations impossible.…”

mentioning

confidence: 99%

A high-throughput assay for quantifying appetite and digestive dynamics

Jordi

Guggiana-Nilo

Soucy

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Jordi J, Guggiana-Nilo D, Soucy E, Song EY, Wee CL, Engert F. A high-throughput assay for quantifying appetite and digestive dynamics. Am J Physiol Regul Integr Comp Physiol 309: R345-R357, 2015. First published June 24, 2015 doi:10.1152/ajpregu.00225.2015.-Food intake and digestion are vital functions, and their dysregulation is fundamental for many human diseases. Current methods do not support their dynamic quantification on large scales in unrestrained vertebrates. Here, we combine an infrared macroscope with fluorescently labeled food to quantify feeding behavior and intestinal nutrient metabolism with high temporal resolution, sensitivity, and throughput in naturally behaving zebrafish larvae. Using this method and rate-based modeling, we demonstrate that zebrafish larvae match nutrient intake to their bodily demand and that larvae adjust their digestion rate, according to the ingested meal size. Such adaptive feedback mechanisms make this model system amenable to identify potential chemical modulators. As proof of concept, we demonstrate that nicotine, L-lysine, ghrelin, and insulin have analogous impact on food intake as in mammals. Consequently, the method presented here will promote large-scale translational research of food intake and digestive function in a naturally behaving vertebrate.appetite; hunger; satiation; satiety; DiR' dye FOOD INTAKE AND DIGESTION are key physiological processes that provide nutrients to drive all bodily functions. Nutrient intake is matched to nutritional needs by the brain-a process termed nutrient homeostasis-using an intertwined organism-wide array of extrinsic and intrinsic cues coding food availability and demand (2, 42). Dysfunction of feeding and digestive behavior is at the root of global health problems, such as obesity, malnutrition, and Type 2 diabetes, among many others, and, therefore, a deeper understanding of feeding and digestive behavior is of high importance (25).Drugs or genetic manipulations that alter food intake or digestion are highly desirable remedies for food-related disorders. To screen for genes or small molecules with clinically desirable impact, the technology of choice needs to support the analyses of hundreds to thousands of individual animals. Until now, large-scale studies of feeding behavior have solely been feasible in small invertebrates such as Drosophila, but were constrained to 20 -50 conditions in vertebrates, thereby making large-scale screens elusive (12,17,35). Technically, even more demanding than measuring food intake is the quantification of nutrient digestion, as there is no direct optical access to the gastrointestinal tract in most species. More specialized technologies, such as bioluminescence, MRI, or computed tomography, have been valuable to generate insights into in vivo dynamics of digestive function (10,18,19,31). However, all of these methods require immobilization of the experimental subject to reduce motion artifacts, thereby making concurrent behavioral observations impossible. Consequently, quantifying the dy...

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“…The use of rats as animal models of human gastric emptying and intestinal motility has a long history for healthy or pathological conditions and is routinely used for screening purposes or mechanism investigation. , Similar patterns of nutrients and xenobiotics effects on gastric emptying have been observed between human and rat. ,, Based on this background, a rat experiment of gastric emptying measurement based on a published protocol was selected to study the potential formulation effect on stomach motility.…”

Section: Discussionmentioning

confidence: 99%

“…20 The rat remains the most widely used rodent species in gastrointestinal safety evaluation including gastrointestinal motility assessment. 21 The use of rats as animal models of human gastric emptying and intestinal motility has a long history for healthy 22 or pathological conditions 23 and is routinely used for screening purposes 24 or mechanism investigation. 25,26 Similar patterns of nutrients and xenobiotics effects on gastric emptying have been observed between human and rat.…”

Section: ■ Discussionmentioning

confidence: 99%

Investigating the Discriminatory Power of BCS-Biowaiver in Vitro Methodology to Detect Bioavailability Differences between Immediate Release Products Containing a Class I Drug

et al. 2015

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The purpose of this work is to investigate the discriminatory power of the Biopharmaceutics Classification System (BCS)-biowaiver in vitro methodology, i.e., to investigate if a BCS-biowaiver approach would have detected the Cmax differences observed between two zolpidem tablets and to identify the cause of the in vivo difference. Several dissolution conditions were tested with three zolpidem formulations: the reference (Stilnox), a bioequivalent formulation (BE), and a nonbioequivalent formulation (N-BE). Zolpidem is highly soluble at pH 1.2, 4.5, and 6.8. Its permeability in Caco-2 cells is higher than that of metoprolol and its transport mechanism is passive diffusion. None of the excipients (alone or in combination) showed any effect on permeability. All formulations dissolved more than 85% in 15 min in the paddle apparatus at 50 rpm in all dissolution media. However, at 30 rpm the nonbioequivalent formulation exhibited a slower dissolution rate. A slower gastric emptying rate was also observed in rats for the nonbioequivalent formulation. A slower disintegration and dissolution or a delay in gastric emptying might explain the Cmax infra-bioavailability for a highly permeable drug with short half-life. The BCS-biowaiver approach would have declared bioequivalence, although the in vivo study was not conclusive but detected a 14% mean difference in Cmax that precluded the bioequivalence demonstration. Nonetheless, these findings suggest that a slower dissolution rate is more discriminatory and that rotation speeds higher than 50 rpm should not be used in BCS-biowaivers, even if a coning effect occurs.

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Novel antidiabetic nutrients identified by in vivo screening for gastric secretion and emptying regulation in rats

Abstract: Jordi J, Herzog B, Lutz TA, Verrey F. Novel antidiabetic nutrients identified by in vivo screening for gastric secretion and emptying regulation in rats.

Cited by 6 publications

References 42 publications

Effects of Intragastric Administration of Tryptophan on the Blood Glucose Response to a Nutrient Drink and Energy Intake, in Lean and Obese Men

Effects of Intragastric Administration of Tryptophan on the Blood Glucose Response to a Nutrient Drink and Energy Intake, in Lean and Obese Men

A high-throughput assay for quantifying appetite and digestive dynamics

Investigating the Discriminatory Power of BCS-Biowaiver in Vitro Methodology to Detect Bioavailability Differences between Immediate Release Products Containing a Class I Drug

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