Loperamide Inhibits the Enhanced Intestinal Glucose Absorption of Cystic Fibrosis In Vitro

Hardcastle, J; Hardcastle, P T; Taylor, C J

doi:10.1203/00006450-199403000-00016

Cited by 5 publications

(5 citation statements)

References 14 publications

(14 reference statements)

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“…Despite the rather similar molecular size of L‐rhamnose and xylose, the current results suggest that they are absorbed by different mechanisms, both accelerated in CF. The fact that other studies have shown an enhanced active intestinal transport of glucose in CF (1,2) and that the IP of xylose was increased in this study, supports the idea of a common or related transport system for the two sugars. It has been suggested that xylose uses the active transport system of glucose but has a lower affinity (33,34).…”

Section: Discussionsupporting

confidence: 89%

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Intestinal Permeability in Cystic Fibrosis in Relation to Genotype

Hallberg,

Grzegorczyk,

Larson

et al. 1997

J. pediatr. gastroenterol. nutr.

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Background:The purpose of this study was to investigate whether the increased intestinal permeability (IP) seen in patients with cystic fibrosis (CF) is correlated with the basic defect, as revealed by the patient's genotype, and/or whether the intestinal disturbance reflects secondary abnormalities such as essential fatty acid deficiency.Methods:Nineteen CF patients were compared with nine age‐ and sex‐ matched healthy controls. IP was evaluated by studying urinary excretion for 5 hours after a test meal containing lactulose, L‐rhamnose and xylose in water. Urine was analyzed for carbohydrates, and blood samples were taken for determination of the fatty acid pattern of serum phospholipids. The CF patients were grouped according to genotype: homozygous for ΔF508, heterozygous for ΔF508, or unidentified.Results:Patients who were homozygous (n = 9) or heterzygous (n = 6) for ΔF508 had significantly higher lactulose/L‐rhamnose excretion ratios (mean(range) values of 0.08(0.05‐0.13) and 0.09(0.03‐0.13), respectively) than patients (n = 4) with unidentified genotypes [0.03(0.02‐0.05); p = 0.005] or healthy controls [0.02(0.003‐0.06); p = 0.002]. CF patients with EFAD (n = 6) did not differ from those with a normal pattern of serum phospholipid fatty acids, the lactulose/L‐rhamnose excretion ratio being 0.08(0.02‐0.13) and 0.07(0.03‐0.12), respectively.Conclusions:These data show that the IP in CF was related to patient genotype; those homozygozous or heterozygous for ΔF508 having a significantly increased IP compared with patients with unidentified genotypes, who had IP values within the normal range.

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Section: Discussionsupporting

confidence: 89%

“…Several studies have provided evidence of abnormalities of the small intestine in patients with CF. These abnormalities include altered secretory function (1), enhanced active transport of glucose (1,2), alterations in amino acid absorption (3), and increased intestinal permeability (IP) (4‐8).…”

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confidence: 99%

Intestinal Permeability in Cystic Fibrosis in Relation to Genotype

Hallberg,

Grzegorczyk,

Larson

et al. 1997

J. pediatr. gastroenterol. nutr.

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“…We observed peak short‐circuit current responses to a stimulus of 45 mM glucose in mice, consistent with saturation of SGLT1‐faciliated glucose transport at 30–50 mM glucose in rat jejunum (Kellett & Helliwell, 2000 ). In Ussing chamber studies using human small intestine, active glucose transport was maximal at 35–65 mM luminal glucose (Hardcastle et al., 1994 ; Kroesen et al., 2002 ; Larsen et al., 2001 ; Puthanmadhom Narayanan et al., 2021 ). Regional luminal glucose concentrations measured in vivo via indwelling catheters ranged from 2 to 48 mM glucose, in rodents, rabbits and dogs fed standard laboratory diets (Ferraris et al., 1990 ), confirming that the glucose concentrations we used in Ussing experiments were physiological.…”

Section: Discussionmentioning

confidence: 99%

Active glucose transport varies by small intestinal region and oestrous cycle stage in mice

Overduin

Wardill

Young

et al. 2023

Experimental Physiology

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Food intake changes across the ovarian cycle in rodents and humans, with a nadir during the pre-ovulatory phase and a peak during the luteal phase. However, it is unknown whether the rate of intestinal glucose absorption also changes. We therefore mounted small intestinal sections from C57BL/6 female mice (8-9 weeks old) in Ussing chambers and measured active ex vivo glucose transport via the change in short-circuit current (∆I sc ) induced by glucose. Tissue viability was confirmed by a positive ∆I sc response to 100 µM carbachol following each experiment. Active glucose transport, assessed after addition of 5, 10, 25 or 45 mM D-glucose to the mucosal chamber, was highest at 45 mM glucose in the distal jejunum compared to duodenum and ileum (P < 0.01). Incubation with the sodium-glucose cotransporter 1 (SGLT1) inhibitor phlorizin reduced active glucose transport in a dose-dependent manner in all regions (P < 0.01). Active glucose uptake induced by addition of 45 mM glucose to the mucosal chamber in the absence or presence of phlorizin was assessed in jejunum at each oestrous cycle stage (n = 9-10 mice per stage). Overall, active glucose uptake was lower at oestrus compared to pro-oestrus (P = 0.025). This study establishes an ex vivo method to measure region-specific glucose transport in the mouse small intestine.Our results provide the first direct evidence that SGLT1-mediated glucose transport in the jejunum changes across the ovarian cycle. The mechanisms underlying these adaptations in nutrient absorption remain to be elucidated.

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“…It is possible that CFTR may affect absorptive processes in addition to its known effects on secretion. In jejunal biopsies from CF patients the Na ‡ -dependent absorption of sugars and amino acids is enhanced, a change that reflects an increase in the maximum capacity of the absorptive process (Baxter et al 1990;Hardcastle et al 1994). The development of transgenic CF mouse models has provided an opportunity to study the transport activity of CF intestine in more detail (Grubb & Gabriel 1997).…”

Section: Introductionmentioning

confidence: 99%

Small intestinal glucose absorption in cystic fibrosis: a study in human and transgenic ΔF508 cystic fibrosis mouse tissues

Hardcastle

Harwood

Taylor

2004

Journal of Pharmacy and Pharmacology

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Intestinal transport is disturbed in cystic fibrosis (CF), with both defective Cl- secretion and changes in absorption being reported. We have examined the effects of the disease on Na(+)-dependent glucose absorption by the small intestine. Active glucose absorption was monitored as changes in short-circuit current (SCC) in intact and stripped intestinal sheets from normal (Swiss) and transgenic CF (Cftr(tm1Eur) and Cftr(tm2Cam)) mice with the DeltaF508 mutation, and in jejunal biopsies from children with CF and normal controls. Na(+)-dependent glucose uptake at the luminal membrane was measured in brush-border membrane vesicles (BBMVs). Intact and stripped sheets of jejunum and midintestine from Swiss mice exhibited a concentration-dependent increase in SCC with glucose. Apparent Km values were similar in the two preparations, but the apparent Vmax was greater in stripped sheets. This difference was not due to a loss of neural activity in stripped sheets as tetrodotoxin did not influence the glucose-induced SCC in intact sheets. Similar results were observed in stripped sheets of jejunum and mid-intestine from wild-type Cftr(tm1Eur) mice, but in tissues from CF mice the apparent Vmax value was reduced significantly. A lower Vmax was also obtained in intact sheets of mid-intestine from CF (Cftr(tm2Cam)) mice. Jejunal biopsies from CF patients however, exhibited an enhanced glucose-dependent rise in SCC. Na(+)-dependent uptake by BBMVs from CF (Cftr(tm1Eur)) mice was not reduced compared with wild-type and Swiss BBMVs. It was concluded that, in contrast to human intestine, intestinal glucose absorption was reduced in transgenic mouse models of CF with the DeltaF508 mutation, but that this could not be detected in an isolated preparation of brush-border membranes. Transgenic mouse models of CF may not accurately reflect all aspects of intestinal dysfunction in the human disease.

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Loperamide Inhibits the Enhanced Intestinal Glucose Absorption of Cystic Fibrosis In Vitro

Cited by 5 publications

References 14 publications

Intestinal Permeability in Cystic Fibrosis in Relation to Genotype

Intestinal Permeability in Cystic Fibrosis in Relation to Genotype

Active glucose transport varies by small intestinal region and oestrous cycle stage in mice

Small intestinal glucose absorption in cystic fibrosis: a study in human and transgenic ΔF508 cystic fibrosis mouse tissues

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