Basal secretion is significantly reduced in the ob/ob mouse jejunum compared to lean controls

Abstract

In the ob/ob leptin‐deficient mouse the role of intestinal secretion is unclear. The goal of this study was to characterize jejunal function. We measured transepithelial short circuit current (Isc), across jejunum from ob/ob and lean mice (aged 14 weeks). Basal Isc was significantly decreased in the ob/ob mice (50.5±9.5 μA/cm2, n=5) compared to lean mice (95.2±20.3 μA/cm2, n=4, P<0.05). The Isc in response to forskolin (10 μM, bilateral) was similar in both groups, indicating a comparable cAMP‐dependent Isc. The Isc in response to bumetanide (100 μM, basolateral) and to acetazolamide (100 μM, bilateral) was similar for both groups, indicating analogous Cl− and HCO3− secretory components. Crypt depth was similar for both groups, indicating that structural changes do not contribute towards the reduced Isc of the ob/ob mice. Villi length was significantly increased (~100 μm) in the ob/ob mice, suggesting a greater surface area for absorptive function. Expression of the transporter protein, Glut5 (normalized to GAPDH), was significantly increased 2‐fold in ob/ob mice. These data suggest that basal jejunal Isc in ob/ob mice is ~1/2 that of lean mice, and may reflect a reduced fluidity of the jejunal content in the ob/ob mice, which may contribute to the associated diabetic phenotype. Current studies aim to determine whether the contribution of key epithelial transporters is similarly reduced in the ob/ob mice.