Involvement of PI 3-kinase in IGF-I stimulation of jejunal Na+-K+-ATPase activity and nutrient absorption.
Mechanisms responsible for increased jejunal transport rates observed in tissues treated with orally administered insulin-like growth factor-I (IGF-I) were studied in 5-day-old colostrum-deprived piglets. Human recombinant IGF-I (3.5 mg. kg(-1). day(-1)) or control vehicle was given orogastrically for 4 days. Disaccharidase activity, fructose uptake, and Na+-glucose cotransporter SGLT-1 protein abundance were similar between groups. Oral IGF-I produced greater rates of enterocyte Na+-K+-ATPase activity with no significant differences in Na+-K+-ATPase abundance. Cellular mechanisms responsible for transport changes were studied in Ussing chambers. In control tissues, the presence of IGF-I in mucosal solutions increased basal short-circuit current (I(sc)), potential difference, D-glucose-stimulated I(sc), and Na+-K+-ATPase activity; these changes were abolished by preincubation of tissues with wortmannin, a phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor. The results suggest that the effect of IGF-I on jejunal ion and nutrient transport involves activation of PI 3-kinase and stimulation of Na+-K+-ATPase activity in enterocytes.
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Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Dr. West, Madison, WI 53706, USA. careyh@svm.vetmed.wisc.edu
Carey
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D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005632:Fructose / Q000493:pharmacokinetics; D005947:Glucose / Q000493:pharmacokinetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007583:Jejunum / Q000201:enzymology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011994:Recombinant Proteins; D012016:Reference Values; D051269:Sodium-Glucose Transporter 1; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013552:Swine
D005632:Fructose; D005947:Glucose; D007334:Insulin-Like Growth Factor I; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D019869:Phosphatidylinositol 3-Kinases; D011994:Recombinant Proteins; D051269:Sodium-Glucose Transporter 1; D000254:Sodium-Potassium-Exchanging ATPase; C495674:SLC5A1 protein, human