Effects of some commonly used antidiabetic plant materials on sodium-glucose cotransport through gastrointestinal and renal tubular endothelium in diabetic model rats

Abstract

Diabetes Mellitus (DM) is a major health problem all over the world and there is still need for more ideal therapeutic agents for the management of various types and subtypes of this disorder. Most of the diabetic subjects (90% on an average) suffer from type 2 Diabetes Mellitus (T2DM) followed by the Type 1 DM (T1DM) variety. It is now widely acknowledged that insulin deficiency (due to selective autoimmune damage of pancreatic B cells) is the major cause of T1DM; however, the etiopathogenesis of T2DM is much more complex with varying degrees of involvement of pancreatic B cell dysfunction and peripheral insulin resistance in different populations and subpopulations. Classical therapeutic approaches against DM are primarily based on ameliorating insulin secretary defect or insulin resistance by targeting the relevant cells and tissues in the body. Recently evidences has been generated on the important role of enhanced glucose absorption through gastrointestinal and renal tubular endothelium (mediated by sodium-glucose cotransporters, or SGLTs) in the pathophysiology of T2DM. Accordingly pharmacological research has already started to explore the potential use of the inhibitor of SGLT1 (for GI tract) and SGLT2 (renal tubule) in reducing glucose absorption/reabsorption in these organs. Plants are thought to be a major source of potential antidiabetic agents and evidence are present that many of the plant extracts exert their effects through inhibition of glucose absorption in the gut. The modern drug development initiatives around SGLTs were, in fact, driven by a plant derived compound, phlorizin. In spite of that, the effects of plant extracts on Na-mediated glucose transport have not yet been studied. A major obstacle in this case may be the nonavailability of appropriate animal models on which such plant based studies can be conducted using relatively easy and cost-effective techniques. Under this perspective, the present series of studies were undertaken to characterize the neonatal streptozotocin induced T2DM (nstzT2DM) model rats in terms of their glycemic and insulinemic as well as intestinal and renal glucose absorption/reabsorption (specially in relation to its association with Na) abnormalities. The effects of three commonly used antidiabetic plants (Aegle marmelos, Trigonella feoenum-gracum and Ocimum sanctum) on the above characterized parameters of the nstzT2DM rats were also tested in this study.