Fig. 4: Exogenous PYY rescues EEC-deficient mice from malabsorptive diarrhea and restores normal glucose and dipeptide transport.
From: Enteroendocrine cells couple nutrient sensing to nutrient absorption by regulating ion transport
a Survival curve of wild-type mice (n = 100), EEC-deficient mice (n = 34), EEC-deficient mice treated once daily with 10 μg PYY (n = 25) beginning at postnatal day 10 (P10), and vehicle-treated EEC-deficient mice (n = 18). ****P < 0.0001 comparison of survival curves to untreated mutant by log-rank Mantel–Cox test. b At postnatal day 28, PYY-treated mutant mice experienced significant weight gain compared to vehicle-treated mutant mice (*P = 0.01, n = 5 mice per condition). Statistics calculated by one-way ANOVA. c EEC-deficient mice have intractable watery diarrhea from birth (n = 34 mice; ****P < 0.0001 from wild-type littermates, n = 100 mice). Within 48 h of PYY treatment, EEC-deficient animals improved to slightly soft yet well-defined fecal pellets (n = 25 mice, ****P < 0.0001 from untreated mutant). Vehicle-treated mutant mice did not improve (n = 18 mice). Statistics calculated by one-way ANOVA with Tukey’s multiple comparisons test. d PYY treatment of EEC-deficient animals restored a normal resting Isc to small intestine (n = 6 mice, ****P < 0.0001) and a normal electrogenic response to VIP (n = 6 mice, ****P < 0.0001). Treatment of mutant mice with vehicle did not improve basal Isc (n = 6 mice) or response to VIP (n = 4 mice). Statistics calculated by one-way ANOVA with Tukey’s multiple comparisons test. e PYY treatment restored a normal glucose response in EEC-deficient mouse and human intestine (mouse, n = 6, **P = 0.003; HIO, n = 5, **P = 0.004). Statistics calculated by one-way ANOVA with Tukey’s multiple comparisons test. f Proton transport, as measured by pHrodo MFI, was normalized between mosaic regions in EEC-deficient reporter animals following PYY treatment (n = 2 mice). Statistics calculated by two-way ANOVA with Sidak’s multiple comparisons test. g PYY improved dipeptide transport in EEC-deficient mouse and human intestine. Long-term treatment of EEC-deficient animals and transplanted HIOs with PYY resulted in improved Isc response to Gly-Sar compared to untreated mutant tissue (mouse, n = 6, **P = 0.009; HIO, n = 5, ***P = 0.0001). Vehicle-treated mutant mice did not exhibit improvement in Gly-Sar response (n = 18 mice, **P = 0.002). Statistics calculated by one-way ANOVA with Tukey’s multiple comparisons test. All wild-type and untreated mutant mouse data points are the same as shown in Figs. 1–3, and S2. All error bars are + SEM.
