Resistin-like molecule alpha reduces gallbladder optimal tension

Insulin resistance is associated with increased gallbladder volume and impaired gallbladder emptying. Resistin and resistin-like molecule alpha (RELM-α) are adipose-derived hormones that are believed to mediate insulin resistance. Therefore, we tested the hypothesis that administration of resistin or RELM-α would cause insulin resistance and diminish gallbladder contractility. In two sequential studies 40 eight-week-old nondiabetic lean mice were fed a chow diet for 4 weeks. In Study A, 10 mice received 20 μg of resistin IP, while in Study B 10 mice received 20 μg of RELM-α IP for seven days. In each study, 10 control mice received an equal volume of saline IP for seven days. At 12 weeks animals were fasted and underwent cholecystectomy, and in vitro gallbladder response to neurotransmitters was determined. Serum resistin, RELM-α, glucose, and insulin levels were measured. HOMA index, a measure of insulin resistance, was calculated. RELM-α significantly increased HOMA index. RELM-α decreased gallbladder optimal tension, but did not alter responses to neurotransmitters. Resistin had no effect on HOMA index or on gallbladder optimal tension or response. These data suggest that in nondiabetic lean mice: 1) resistin does not alter insulin resistance or gallbladder optimal tension, but 2) RELM-α increases insulin resistance and reduces gallbladder optimal tension. Therefore, we concluded that RELM-α may play a role in insulin-resistance mediated gallbladder dysmotility.