Effect of growth hormone on intestinal Na⁺/glucose cotransporter activity

Background: Growth hormone (GH) has been used alone or as part of a defined regimen in the treatment of patients with short bowel syndrome; however its mode of action remains unclear. Growth hormone has been shown to increase amino acid, water, and electrolyte absorption from the small intestine. The acute effect of growth hormone on intestinal sugar transport has not been described previously. Methods: Mucosal preparations of rat jejunum were mounted in the Ussing chamber. Growth hormone (2 × 10^-6 M or 8 × 10^-6 M) or vehicle was added to the serosal chamber 1, 3, or 5 hours later. Twenty or 40 minutes after growth hormone addition, 30 mmol/L 3-O-methylglucose was added to both chambers, and the change in short-circuit current (ΔI_SC) was recorded. In separate experiments, tissues were pretreated with phloridzin, an inhibitor of Na⁺/glucose cotransport, before the addition of 3-O-methylglucose. In the final set of experiments, kinetic studies were performed. Results: GH did not induce any alterations in baseline electrical parameters. Only tissues left in the chambers for 5 hours, but not 1 or 3 hours, before GH treatment displayed a greater 3-O-methylglucose-induced ΔI_SC than controls (p < .05). The increase in I_SC induced by 3-O-methylglucose was 100% phloridzin-inhibitable. Kinetic analysis showed that growth hormone administration is associated with an increase in Na⁺/glucose cotransporter maximal velocity (V_max) but no significant change in carrier affinity for substrate (K_m). Conclusions: Growth hormone increases intestinal sugar transport, but only in tissue that has not been exposed to endogenous GH for over 3 hours.