Characterization of the Binding of Drugs to Human Intestinal Fatty Acid Binding Protein (IFABP): Potential Role of IFABP as an Alternative to Albumin for in Vitro-in Vivo Extrapolation of Drug Kinetic Parameters

2009 ◽  
Vol 37 (7) ◽  
pp. 1395-1403 ◽  
Author(s):  
Andrew Rowland ◽  
Kathleen M. Knights ◽  
Peter I. Mackenzie ◽  
John O. Miners
2005 ◽  
Vol 288 (2) ◽  
pp. E292-E297 ◽  
Author(s):  
Jane Shearer ◽  
Patrick T. Fueger ◽  
Jeffrey N. Rottman ◽  
Deanna P. Bracy ◽  
Bert Binas ◽  
...  

The role of heart-type cytosolic fatty acid-binding protein (H-FABP) in mediating whole body and muscle-specific long-chain fatty acid (LCFA) and glucose utilization was examined using exercise as a phenotyping tool. Catheters were chronically implanted in a carotid artery and jugular vein of wild-type (WT, n = 8), heterozygous (H-FABP+/−, n = 8), and null (H-FABP−/−, n = 7) chow-fed C57BL/6J mice, and mice were allowed to recover for 7 days. After a 5-h fast, conscious, unrestrained mice were studied during 30 min of treadmill exercise (0.6 mph). A bolus of [125I]-15-( p-iodophenyl)-3- R, S-methylpentadecanoic acid and 2-deoxy-[3H]glucose was administered to obtain rates of whole body metabolic clearance (MCR) and indexes of muscle LCFA (Rf) and glucose (Rg) utilization. Fasting, nonesterified fatty acids (mM) were elevated in H-FABP−/− mice (2.2 ± 0.9 vs. 1.3 ± 0.1 and 1.3 ± 0.2 for WT and H-FABP+/−). During exercise, blood glucose (mM) increased in WT (11.7 ± 0.8) and H-FABP+/− (12.6 ± 0.9) mice, whereas H-FABP−/− mice developed overt hypoglycemia (4.8 ± 0.8). Examination of tissue-specific and whole body glucose and LCFA utilization demonstrated a dependency on H-FABP with exercise in all tissues examined. Reductions in H-FABP led to decreasing exercise-stimulated Rf and increasing Rg with the most pronounced effects in heart and soleus muscle. Similar results were seen for MCR with decreasing LCFA and increasing glucose clearance with declining levels of H-FABP. These results show that, in vivo, H-FABP has reciprocal effects on glucose and LCFA utilization and whole body fuel homeostasis when metabolic demands are elevated by exercise.


2021 ◽  
Vol 160 (6) ◽  
pp. S-166
Author(s):  
Shuhei Shinoda ◽  
Keith Wirth ◽  
Sayeed Ikramuddin ◽  
David A. Bernlohr ◽  
Masato Yamamoto

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Fernanda Roca Rubio ◽  
Ulrika Eriksson ◽  
Robert J. Brummer ◽  
Julia König

AbstractThe intestinal barrier plays a crucial role in maintaining gut health, and an increased permeability has been linked to several intestinal and extra-intestinal disorders. There is an increasing demand for interventions aimed at strengthening this barrier and for in vivo challenge models to assess their efficiency. This study investigated the effect of sauna-induced dehydration on intestinal barrier function (clinicaltrials.gov: NCT03620825). Twenty healthy subjects underwent three conditions in random order: (1) Sauna dehydration (loss of 3% body weight), (2) non-steroidal anti-inflammatory drug (NSAID) intake, (3) negative control. Intestinal permeability was assessed by a multi-sugar urinary recovery test, while intestinal damage, bacterial translocation and cytokines were assessed by plasma markers. The sauna dehydration protocol resulted in an increase in gastroduodenal and small intestinal permeability. Presumably, this increase occurred without substantial damage to the enterocytes as plasma intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) were not affected. In addition, we observed significant increases in levels of lipopolysaccharide-binding protein (LBP), IL-6 and IL-8, while sCD14, IL-10, IFN-ɣ and TNF-α were not affected. These results suggest that sauna dehydration increased intestinal permeability and could be applied as a new physiological in vivo challenge model for intestinal barrier function.


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