title: Acute interactions between intestinal sugar and calcium transport in vitro.
abstract: Fructose consumption by Americans has increased markedly, whereas Ca(2+) intake has decreased below recommended levels. Because fructose metabolism decreases enterocyte ATP concentrations, we tested the hypothesis that luminal fructose acutely reduces active, diet-inducible Ca(2+) transport in the small intestine. We confirmed that the decrease in ATP concentrations was indeed greater in fructose- compared with glucose-incubated mucosal homogenates from wild-type and was prevented in fructose-incubated homogenates from ketohexokinase (KHK)(-/-) mice. We then induced active Ca(2+) transport by chronically feeding wild-type, fructose transporter glucose transporter 5 (GLUT5)(-/-), as well as KHK(-/-) mice a low Ca(2+) diet and measured transepithelial Ca(2+) transport in everted duodenal sacs incubated in solutions containing glucose, fructose, or their nonmetabolizable analogs. The diet-induced increase in active Ca(2+) transport was proportional to dramatic increases in expression of the Ca(2+)-selective channel transient receptor potential vanilloid family calcium channel 6 as well as of the Ca(2+)-binding protein 9k (CaBP9k) but not that of the voltage-dependent L-type channel Ca(v)1.3. Crypt-villus distribution of CaBP9k seems heterogeneous, but low Ca(2+) diets induce expression in more cells. In contrast, KHK distribution is homogeneous, suggesting that fructose metabolism can occur in all enterocytes. Diet-induced Ca(2+) transport was not enhanced by addition of the enterocyte fuel glutamine and was always greater in sacs of wild-type, GLUT5(-/-), and KHK(-/-) mice incubated with fructose or nonmetabolizable sugars than those incubated with glucose. Thus duodenal Ca(2+) transport is not affected by fructose and enterocyte ATP concentrations but instead may decrease with glucose metabolism, as Ca(2+) transport remains high with 3-O-methylglucose that is also transported by sodium-glucose cotransporter 1 but cannot be metabolized.
authors.affiliation: Dept. of Pharmacology & Physiology, Rutgers Biomedical and Health Sciences, New Jersey Medical School (NJMS 185 South Orange Ave., Newark, NJ 07103. ferraris@njms.rutgers.edu.
authors.forename: Phuntila
authors.initials: P
authors.lastname: Tharabenjasin
authors.forename: Veronique
authors.initials: V
authors.lastname: Douard
authors.forename: Chirag
authors.initials: C
authors.lastname: Patel
authors.forename: Nateetip
authors.initials: N
authors.lastname: Krishnamra
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
authors.forename: Ronaldo P
authors.initials: RP
authors.lastname: Ferraris
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism*; D005631:Fructokinases / Q000378:metabolism; D005632:Fructose / Q000378:metabolism*; D020869:Gene Expression Profiling; D051296:Glucose Transporter Type 5 / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D017136:Ion Transport / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009747:Nutritional Physiological Phenomena; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D051296:Glucose Transporter Type 5; D051269:Sodium-Glucose Transporter 1; D005632:Fructose; D005631:Fructokinases; D002118:Calcium
keywords: calbindin; fructose; glucose; glucose transporter 5; metabolism; nutrition