<span style="font-size:11.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">Antidiabetic activity of heart wood of <i style="mso-bidi-font-style:normal">Pterocarpus marsupium</i> Roxb. and analysis of phytoconstituents^†</span>

363-374The crude powder, ethanolic extract and aqueous, chloroform, hexane and n-butanol soluble fractions of ethanolic extract of heart wood of P. marsupium showed marked improvement on oral glucose tolerance post sucrose load in normal rats. All these fractions except aqueous fraction showed improvement on oral glucose tolerance post sucrose load on streptozotocin (STZ)-induced diabetic rats. The crude powder, ethanolic extract and hexane and n-butanol fractions showed marked decline in blood glucose level on STZ-induced diabetic rats. The ethanolic extract (100 mg/kg body weight) when given to STZ-induced diabetic rats for 10 consecutive days declined blood glucose, improved OGTT and increased their serum insulin levels. The ethanolic extract also showed marked improvement on oral glucose tolerance on high fat-low dosed STZ-induced diabetic rats and neonatally STZ treated rats. The ethanolic extract of P. marsupium also showed marked antidyslipidemic effects on high fat diet fed Syrian golden hamsters. Altered renal and hepatic function markers and serum insulin levels of high fat diet fed-low dosed STZ-treated diabetic rats were also found towards normalization when these animals were treated with ethanolic extract of P. marsupium for 28 consecutive days. The four out of five phenolic C-glycosides isolated from n-butanol fraction of ethanolic extract of P. marsupium enhanced glucose uptake by skeletal muscle cells (C2C12) in a dose dependent manner. It may primarily be concluded that phenolic-C-glycosides present in P. marsupium heart wood are the phytoconstituents responsible for the antihyperglycemic activity and validate the claim of antidiabetic activity of heart wood of <i style="mso-bidi-font-style: normal">P. marsupium

Tinosporaside from <i>Tinospora cordifolia</i> Encourages Skeletal Muscle Glucose Transport through Both PI-3-Kinase- and AMPK-Dependent Mechanisms

The stem of Tinospora cordifolia has been traditionally used in traditional Indian systems of medicine for blood sugar control, without the knowledge of the underlying mechanism and chemical constitution responsible for the observed anti-diabetic effect. In the present study, Tinosporaside, a diterpenoid isolated from the stem of T. cordifolia, was investigated for its effects on glucose utilization in skeletal muscle cells, which was followed by determining the anti-hyperglycemic efficacy in our diabetic db/db mice model. We found that tinosporaside augmented glucose uptake by increasing the translocation of GLUT4 to the plasma membrane in L6 myotubes, upon prolonged exposure for 16 h. Moreover, tinosporaside treatment significantly increased the phosphorylation of protein kinase B/AKT (Ser-473) and 5′ AMP-activated protein kinase (AMPK, Thr-172). These effects were abolished in the presence of the wortmannin and compound C. Administration of tinosporaside to db/db mice improved glucose tolerance and peripheral insulin sensitivity associated with increased gene expression and phosphorylation of the markers of phosphoinositide 3-kinases (PI3Ks) and AMPK signaling in skeletal muscle tissue. The findings revealed that tinosporaside exerted its antidiabetic efficacy by enhancing the rate of glucose utilization in skeletal muscle, mediated by PI3K- and AMPK-dependent signaling mechanisms

Triiodothyronine Acutely Stimulates Glucose Transport into L6 Muscle Cells Without Increasing Surface GLUT4, GLUT1, or GLUT3

Background: Thyroid hormones (THs) act genomically to stimulate glucose transport by elevating glucose transporter (Slc2a) expression and glucose utilization by cells. However, nongenomic effects of THs are now emerging. Here, we assess how triiodothyronine (T-3) acutely affects glucose transport and the content of GLUT4, GLUT1, and GLUT3 at the surface of muscle cells, and possible interactions between T-3 and insulin action. Methods: Differentiated L6 myotubes transfected with myc-tagged Slc2a4 (L6-GLUT4myc) or Slc2a1 (L6-GLUT1myc) and wild-type L6 myotubes were studied in the following conditions: control, hypothyroid (Tx), Tx plus T3, Tx plus insulin, and Tx plus insulin and T-3. Results: Glucose uptake and GLUT4 content at the cell surface decreased in the Tx group relative to controls. T-3 treatment for 30 minutes increased glucose transport into L6-GLUT4myc cells without altering surface GLUT4 content, which increased only thereafter. The total amount of GLUT4 protein remained unchanged among the groups studied. The surface GLUT1 content of L6-GLUT1myc cells also remained unaltered after T-3 treatment; however, in these cells glucose transport was not stimulated by T-3. In wild-type L6 cells, although T-3 treatment increased the total amount of GLUT3, it did not change the surface GLUT3 content. Moreover, within 30 minutes, T-3 stimulation of glucose uptake was additive to that of insulin in L6-GLUT4myc cells. As expected, insulin elevated surface GLUT4 content and glucose uptake. However, interestingly, surface GLUT4 content remained unchanged or even dropped with T-3 plus insulin. Conclusions: These data reveal that T-3 rapidly increases glucose uptake in L6-GLUT4myc cells, which, at least for 30 minutes, did not depend on an increment in GLUT4 at the cell surface yet potentiates insulin action. We propose that this rapid T-3 effect involves activation of GLUT4 transporters at the cell surface, but cannot discount the involvement of an unknown GLUT.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP: 08/56446-9, 2006/52830-3]Fundacao de Amparo a Pesquisa do Estado de Sao PauloConselho Nacional de Pesquisa e Desenvolvimento (CNPq), BrazilCNPq Conselho Nacional de Pesquisa e Desenvolvimento (Brazil)Canadian Institutes of Health [MT 12601]Canadian Institutes of Healt

Antidiabetic Property of <i>Symplocos cochinchinensis</i> Is Mediated by Inhibition of Alpha Glucosidase and Enhanced Insulin Sensitivity

<div><p>The study is designed to find out the biochemical basis of antidiabetic property of <i>Symplocos cochinchinensis</i> (SC), the main ingredient of ‘<i>Nisakathakadi</i>’ an <i>Ayurvedic</i> decoction for diabetes. Since diabetes is a multifactorial disease, ethanolic extract of the bark (SCE) and its fractions (hexane, dichloromethane, ethyl acetate and 90% ethanol) were evaluated by <i>in vitro</i> methods against multiple targets relevant to diabetes such as the alpha glucosidase inhibition, glucose uptake, adipogenic potential, oxidative stress, pancreatic beta cell proliferation, inhibition of protein glycation, protein tyrosine phosphatase-1B (PTP-1B) and dipeptidyl peptidase-IV (DPP-IV). Among the extracts, SCE exhibited comparatively better activity like alpha glucosidase inhibition (IC₅₀ value-82.07±2.10 µg/mL), insulin dependent glucose uptake (3 fold increase) in L6 myotubes, pancreatic beta cell regeneration in RIN-m5F (3.5 fold increase) and reduced triglyceride accumulation (22% decrease) in 3T3L1 cells, protection from hyperglycemia induced generation of reactive oxygen species in HepG2 cells (59.57% decrease) with moderate antiglycation and PTP-1B inhibition. Chemical characterization by HPLC revealed the superiority of SCE over other extracts due to presence and quantity of bioactives (beta-sitosterol, phloretin 2′glucoside, oleanolic acid) in addition to minerals like magnesium, calcium, potassium, sodium, zinc and manganese. So SCE has been subjected to oral sucrose tolerance test to evaluate its antihyperglycemic property in mild diabetic and diabetic animal models. SCE showed significant antihyperglycemic activity in <i>in vivo</i> diabetic models. We conclude that SC mediates the antidiabetic activity mainly via alpha glucosidase inhibition, improved insulin sensitivity, with moderate antiglycation and antioxidant activity.</p></div