Abstracts
1997 Digestive Disease Week

Glucocorticoids accelerate intestinal nutrient transport in a time-related, substrate-specific, and IGF-I-independent fashion.

P Iannoli, J Miller, C Ryan, H Sax. Department of Surgery, University of Rochester, Rochester, NY.

Purpose: GC mediate skeletal muscle proteolysis during critical illness to provide substrates for hepatic acute phase protein synthesis and gluconeogenesis. The effects of hypercortisolemia on splanchnic substrate uptake are not well defined. This study characterizes intestinal nutrient transport in response to acute elevations of plasma GC levels. Methods: New Zealand White rabbits were randomized to GC (dexamethasone, 2 mg/kg IM) or vehicle and were sacrificed 8, 16, or 24 hrs after treatment. Brush-border membrane vesicles were prepared from pooled small intestinal mucosa and uptake of tritiated glutamine (Gln), glucose, alanine (Ala), leucine (Leu), and arginine (Arg) was quantified in the presence and absence of a Na⁺ gradient. Plasma insulin-like growth factor-I (IGF-I) levels were determined by RIA. A pathologist blinded to groups evaluated mucosal morphology and villus heights. Results: Na⁺-dependent uptake (pmol/mg protein/10 sec) and IGF-I levels (ng/mL) are reported as mean ± SEM.

*p<0.05 vs control. psip<0.05 vs control, 8 hrs, and 16 hrs (ANOVA).
Group    N   Gln     Glucose      Ala         Leu           Arg   IGF-I
control  4   216±18   26±17       102±14      449±28        6±4   50±2
8 hrs    5   267±13  399±7*       124±9       538±20*      17±9   45±4
16 hrs   4   240±12  246±19       116±14      474±11       13±3   38±7
24 hrs   5   278±22  542±18^psi  174±15^psi 612±22^psi  25±11  40±12

(1) GC accelerated Na⁺-dependent glucose and Leu uptake at 8 hrs (77% and 20%) and 24 hrs (140% and 36%). (2) Na⁺-dependent Ala transport increased by 70% at 24 hrs. (3) GC upregulated Na⁺-independent transport by 240% (vs control) for all substrates at 24 hrs (p<0.05, data not shown). (4) GC did not affect Na⁺-dependent Gln or Arg uptake, IGF-I levels, mucosal morphology, or villus heights. Conclusions: (1) The bimodal increase in Na⁺-dependent glucose and Leu transport suggests increased enterocyte expression of a preformed pool of transport proteins at 8 hrs, depletion of this pool by 16 hrs, and de novo synthesis of transporters by transcriptional or translational upregulation at 24 hrs. (2) Globally enhanced Na⁺-independent transport suggests accelerated passive diffusion or increased plasma membrane fluidity. (3) GC acutely upregulate intestinal nutrient transport in a time-related and substrate-specific fashion via plasma IGF-I independent pathways, thereby supporting increased cellular metabolism, including hepatic gluconeogenesis and protein synthesis, during critical illness.