New research shows that reduced expression of electrolyte transport proteins contributes to diabetic diarrhoea, a gastrointestinal complication that is common in patients with type 1 diabetes mellitus (T1DM). In mice with streptozotocin-induced T1DM, the rate of fluid absorption in the small intestine (a marker of diarrhoea) was 50% lower than that in nondiabetic control mice. Associated with this reduction, expression of Na+/H+ exchanger 3 (NHE-3) and several proteins that bind NHE-3 were reduced in the intestinal brush border membrane (BBM). Under physiological conditions, NHE-3 and its binding proteins formed complexes that facilitated trafficking of NHE-3 to the BBM, consequent NHE-3 activity and ensuing fluid absorption; however, under diabetic conditions, NHE-3 complex formation was disrupted. Treatment of diabetic mice with insulin reconstituted NHE-3 complexes and restored fluid absorption. The findings highlight the pivotal role of multiprotein complex assembly in restoring fluid absorption in T1DM.