In vitro Modulation of Pancreatic Insulin Secretion and Extra Pancreatic Insulin Action, Enzymatic Starch Digestion and Protein Glycation by Terminalia chebula Extracts.

Aim: Traditional plant treatments have been used throughout the world for the therapy of diabetes mellitus. Study Design: Using multiple in vitro models; this study was designed to investigate the efficacy and mode of action of Terminalia chebula Retz. (Combretaceae) used traditionally for treatment of diabetes. Place and Duration of Study: School of Biomedical Sciences, University of Ulster, 2001- 2004. Results: T. chebula aqueous extract stimulated basal insulin output and potentiated glucose-stimulated insulin secretion concentration-dependently in the clonal pancreatic beta cell line, BRIN-BD11 (p<0.001). The insulin secretory activity of plant extract was abolished in the absence of extracellular Ca2+ and by inhibitors of cellular Ca2+ uptake, diazoxide and verapamil, (p<0.001). Furthermore, the extract increased insulin secretion in depolarised cells and augmented insulin secretion triggered by IBMX, but not by tolbutamide or glibenclamide. T. chebula extract did not display insulin mimetic activity but it enhanced insulin-stimulated glucose transport in 3T3 L1 adipocytes by 280% (p<0.001). At (0.5-5.0mg/mL) concentrations, the extract also produced 22-84% (p<0.001) decrease in starch digestion In vitro and inhibited protein glycation (p<0.001) at 1mg/ml aqueous extract. Conclusion: This study has revealed that water soluble bioactive principles in T.chebula extract stimulate insulin secretion, enhance insulin action and inhibit both protein glycation and starch digestion. The former actions are dependent on the bioeffective component(s) in the plant being absorbed intact. Future work assessing the use of Terminalia chebula as dietary adjunct or as a source of active antidiabetic agents may provide new opportunities for the treatment of diabetes

Emblica officinalis Stimulates the Secretion and Action of Insulin and Inhibits Starch Digestion and Protein Glycation In vitro.

Aim: Medicinal, edible and aromatic plants and natural products have been used worldwide for the management of diabetes mellitus. The aim of this study was to investigate the efficacy and mode of action of Emblica officinalis Gaertn. (Phyllanthaceae) used traditionally for treatment of diabetes. Study Design: Using multiple In vitro models; this study was designed to investigate the antidiabetes efficacy and mode of action of E. officinalis. Place and Duration of Study: School of Biomedical Sciences, University of Ulster, 2001- 2004 Results: E. officinalis aqueous extracts (AEs) stimulated basal insulin output and potentiated glucose-stimulated insulin secretion concentration-dependently in the clonal pancreatic beta cell line, BRIN-BD11 (p<0.001). The insulin secretory activity of plant extract was abolished in the absence of extracellular Ca2+ and by inhibitors of cellular Ca2+ uptake, diazoxide (p<0.001, n=8). Furthermore, the extract increased insulin secretion in depolarised cells and further augmented insulin secretion triggered by IBMX and tolbutamide. E. officinalis AE (1 mg/mL) displayed insulin mimetic activity (230%, p<0.001). Furthermore, it enhanced insulin-stimulated glucose transport in 3T3 L1 adipocytes by 460% (p<0.001). E. officinalis augmented also synergistically (p<0.001) insulin action, when co-incubated with insulin sensitizers; metformin (2.4-fold), vanadate (4.9-fold), tungstate (4.8-fold) and molybdate (6-fold). At higher concentrations (0.5-5 mg/mL), the extract also produced 8-74% (p<0.001) decrease in enzymatic starch digestion In vitro. E. officinalis AEs (1-50 mg/mL) inhibited protein glycation 44-87% (p<0.001). Conclusion: This study has revealed that water soluble bioactive principles in E. officinalis extract stimulate insulin secretion, enhance insulin action and inhibit both protein glycation and starch digestion. The former actions are dependent on the bioeffective component (s) in the plant being absorbed intact. Future work assessing the use of Emblica officinalis as adjunctive therapeutic nutraceutical or as a source of bioactive antidiabetic principles may provide new opportunities for the integrated management/prevention/reversal of diabetes.

Efectos de dos esquemas de TH combinada cíclica sobre la presión arterial, lipoproteínas, índices de resistencia a la insulina y cociente TG/C-HDL en mujeres posmenopáusicas hipertensas

Objetivos: Comparar el efecto de dos esquemas de terapia hormonal (TH) combinada cíclica, sobre la presión arterial (PA), índices de resistencia a la insulina y cociente Tg/C-HDL en mujeres postmenopáusicas hipertensas. Métodos: Estudio clínico realizado en 19 posmenopáusicas hipertensas. Todas iniciaron la TH con estrógenos equinos conjugados (Premarin®: 0,625mg) durante 8 semanas (TH-O). Después de un periodo de 4 semanas sin tratamiento se inició TH transdérmica (TH-TD) con 17βestradiol (Estraderm®, 50mg,) durante el mismo período de tiempo. Acetato de medroxiprogesterona (5mg, Provera®) fue administrado durante las semanas 3a-4a y 7a-8a de cada esquema de tratamiento. Se registró la PA y se tomaron muestras de sangre en condición basal y después de cada período de tratamiento para determinación de lípidos, glucemia, insulina, FSH, estradiol, androstenediona y DHEAS. Resultados: La TH disminuyó la PA significativamente (p<0,05), la TH-TD tuvo un efecto más favorable. La TH-O disminuyó significativamente el Ct, C-LDL, apoB, índices Tg/C-HDL, Ct/C-HDL y aumentó significativamente el C-HDL. El C/C-LDL no fue modificado por la TH. La concentración de Tg disminuyó significativamente durante ambos esquemas de tratamiento, con un efecto mayor durante la TH-TD. La glucosa e insulina en ayunas y en respuesta a la carga de glucosa oral fueron similares en ambos grupos; la TH-TD aumentó significativamente los índices de sensibilidad (ISI y QUICKI) y disminuyó el índice HOMAIR. La androstenediona disminuyó (p<0,05) con ambos esquemas. Conclusiones: La TH combinada, cíclica tiene efectos favorables sobre la PA, dislipidemia, índice Tg/C-HDL e índices de acción insulínica, lo cual podría disminuir el riesgo de ECV en la mujer posmenopáusica hipertensa. Se sugiere que en pacientes postmenopáusicas con hipertrigliceridemia e hipertensión arterial la TH-TD debería ser considerada como primera opción terapéutica.

Abstract Objectives: To compare the effect of two routes of hormonal therapy (HT) on blood pressure, insulin resistance indexes, Tg/ HDL-C ratio in postmenopausal hypertensive women. Méthods: A clinical study was performed in 19 postmenopausal women. All women were treated with equine conjugated estrogens (Premarin®: 0,625mg) for 8 weeks (O-HT). After 4 weeks period without treatment, patients were switched to transdermal estrogen therapy (TD-HT) using 17βestradiol (Estraderm®, 50mg). Medroxyprogesterone (5mg, Provera®) acetate was administered during 3rd-4th week and seventh-eighth week in each treatment cycle. Blood pressure and blood samples were taken at baseline and after each period o treatment. Laboratory protocol included determinations of FSH, estradiol, androstendione, DHEAS and glucose and insulin during a standard oral glucose test. Results: HT caused a significant decrease in BP but TD-HT was more efficient (p<0,05). Oral treatment was associated with a significant decrease in Tg/C-HDL, Ct/C-HDL indexes and a significant increase in HDL-C. Plasma Tg decreased significantly after both routes of treatment with more pronounced effect during TD-HT. No significant differences between groups were observed in plasma glucose and insulin during fasting and post oral glucose load. TD-HT showed a significant decrease in HOMA-IR and a significant increase in sensitivity indexes QUICKI and ISI. Serum androstenedione levels were decreased after both routes of treatment (p<0,05). Conclusions: Combined cyclical HT has beneficial effects on blood pressure, lipoproteins, Tg/C-HDL ratio and insulin action indexes leading to a lower risk of cardiovascular disease in postmenopausal hypertensive women. We suggest that in this population, transdermal HT should be considered as a first therapeutic option.

The Treatment Strategy for Diabetes Mellitus by Kampo Medicine / 日本東洋医学雑誌

Recently in Japan, the numbers of diabetic patients have been increased to 7.4 million and to 16.2 millions if the subjects of impaired glucose tolerance are added. Most Japanese diabetic patients are type 2 (non-insulin dependent). Decreased secretion of insulin and insulin resistance play important roles on the occurrence and progression of type 2 diabetes.<br>Long-established systems of traditional medicine have evolved from systematic recordings of human evidence for more than 3 thousands years. In addition the traditional Chinese medicinal philosophy is one of the oldest medical sciences in the world and has a long-standing history in the usage of herbal medicinals. Nowadays the use of complementary/alternative medicine and especially the consumption of botanicals has been increasing rapidly worldwide.<br>1. Clinical Studies<br>The management of diabetic neuropathy is one of the most difficult clinical problems. Among 65 patients with diabetic neuropathy who suffered from numbness of lower extremities 43 (66.2%) experienced some degree of improvement after oral administration of Goshajinkigan (GJG). Following our first report, more than 10 papers were published in Japan and almost same results were obtained. In a well-controlled comparative study, the efficacy of GJG and mecobalamin in diabetic neuropathy was estimated. After oral administration of GJG, the general improvement rate was 80.0%, while it was 48.1% in mecobalamin. The difference between the two groups was statistically significant (P<0.01). These results suggested that GJG is a useful medicine for amelioration of numbness due to diabetic neuropathy.<br>2. Animal experimental studies<br>Regular physical training has been known to be beneficial in the prevention and the treatment of life-style related diseases such as type 2 diabetes. However, it is very difficult for diabetic patients to continue physical exercise training for a long time. Troglitazone has insulin-sensitizing actions but it withdrew because of severe fatal hepato-toxic actions. Therefore development of insulin-sensitizing medicine without significant side-effects have been expected.<br>Chinese herbal medicine has less frequent side effects when compared to modern western medicine.<br>In the present study, the effect of GJG on insulin resistance in streptozotocin (STZ, 50mg kg^-1 BW, ivy.)-induced diabetic rats was examined by means of the euglycemic clamp procedure.<br>The improvement of impaired insulin action in STZ-diabetic rats by single and repeated administration of GJG may be due, at least in part, to enhance insulin signaling, and subsequent ameliorated production of NO. In conclusion, <br>(1) Diagnosis and primary treatment to reduce blood glucose including diet, exercise, oral hypoglycemic agents and insulin should be practiced by western style medical sciences. (2) Kampo medication is useful for the prevention and treatment of diabetic complications. (3) Kampo medicine has the possibility of prevention of type 2 diabetes.

Effects of different types of physical training on insulin action in human peripheral tissues. Use of the euglycemic clamp technique / 体力科学

Physical training has been shown to improve glucose tolerance and insulin action in peripheral tissues. In the present study, regular (R) and high (H) -dose euglycemic clamp procedures were performed to determine the effects of different types of physical training on insulin action (sensitivity/responsiveness) in 10 long-distance runners (LR), 10 weight-lifters (WL) and 12 healthy controls (HC), The amount of infused glucose (glucose metabolism, GM) during euglycemic clamping is a measure of the peripheral tissue sensitivity and/or responsiveness to insulin. For R clamping, when GM was calculated per unit body weight (BW), GM in LR (11.92±1.22 mg/kg BW·min) and WL (9.28±0.63 mg/kg BW·min) was significantly (P<0.05) higher than that in HC (7.44±0.39 mg/kg BW·min) . When calculated per unit lean body mass (LBM), LR (15.07±1.56 mg/kg LBM·min) differed from HC (9, 15±0.59 mg/kg LBM·min, P<0.05), whereas the value in WL (11.50±0.93mg/kg LBM·min) was identical to that in HC. For H clamping, there was no significant change in these three groups when GM was calculated per unit BW or LBM. These results suggest that enhancement of insulin action by physical training is due to an increase in insulin sensitivity, rather than to an increase in insulin responsiveness, and that aerobic exercise, for example long-distance running, is more effective for the improvement of decreased sensitivity to insulin, which is observed in patients with simple obesity and diabetes, than anaerobic exercise such as weight-lifting.