Modulation of aquaporins expressions and its impact on alleviating diabetic complications in rats: role of Citrullus colocynthis

Abstract

Background: Aquaporins (AQPs) belong to a class of small, integral membrane proteins that enable water transfer across the plasma membranes of cells as a reaction to osmotic gradients. There are 13 known types of AQPs in humans (AQP0 to AQP12), which are expressed in various organs such as the kidney, brain, liver, lungs, and salivary glands. In patient with diabetes mellitus, a reduction in salivary secretion is noted in concurrence with low salivary AQP5 levels. The Citrullus colocynthis (CC) extracts were reported to have beneficial effects on glucose homeostasis and body weight maintenance, in either alloxan- or streptozotocin (STZ)-induced diabetic rats through exerting insulinotropic effect. Aims and Objective: To check the changes in AQPs expression and to understand the antidiabetic effect of CC as a medicinal herb in STZ-induced diabetic rats. Materials and Methods: Forty-two male Wistar rats were assigned equally into six groups. The first and second groups were kept as control groups: the first remained without treatment, but the second received CC orally. Diabetes was induced by a single intraperitoneal (i.p) injection of STZ (60 mg/kg b.w.) in the remaining four groups. Three diabetic groups were treated with insulin or CC or both together for 4 weeks. The remaining diabetic group was left untreated as control diabetic group. Blood and organs were taken for biochemical, gene expression, and immunohistochemistry examinations. Result: Diabetic rats displayed increases in blood glucose, lipid profile, liver, and kidney parameters, which were restored significantly to normal with insulin or CC or both. At molecular level, diabetic rats showed significant downregulation in mRNA expressions of antioxidant enzymes, insulin receptor substrate 1 and 2, pyruvate kinase, GLUT-2 in liver and of AQP1, AQP5, AQP7, and AQP8 expressions in kidney, salivary gland, and pancreas, respectively, and normalized significantly by insulin or CC or in combination administrations. Expressions of phosphoenol pyruvate carboxykinase in liver and of AQP2 and AQP3 in kidney were upregulated in diabetic rats and returned to normal completely by insulin alone or CC or their combination. Values were statistically significant at p < 0.05. Immunohistochemical examinations revealed a downregulation of insulin and GLUT-2 in pancreas and upregulation of AQP2 in kidney of diabetic rats, but treatments with CC augmented insulin effect and restored their expression to normal levels. Conclusion: Current results concluded that AQPs could be a promising target for drug development. Moreover, Citrullus colocynthis extract acts as antidiabetic medicinal herb, which has been confirmed by its molecular and immunohistochemical effects.