Ellagic acid in Emblica officinalis exerts anti-diabetic activity through the action on ß-cells of pancreas.

PURPOSE: The present study was undertaken to explore the possible anti-diabetic mechanism(s) of Emblica officinalis (EO) and its active constituent, ellagic acid (EA), in vitro and in vivo. METHOD: Neonatal streptozotocin-induced non-obese type 2 diabetic rats were treated with a methanolic extract of EO (250 or 500 mg/kg) for 28 days, and blood glucose, serum insulin, and plasma antioxidant status were measured. Insulin and glucagon immunostaining and morphometry were performed in pancreatic section, and liver TBARS and GSH levels were measured. Additionally, EA was tested for glucose-stimulated insulin secretion and glucose tolerance test. RESULTS: Treatment with EO extract resulted in a significant decrease in the fasting blood glucose in a dose- and time-dependent manner in the diabetic rats. It significantly increased serum insulin in the diabetic rats in a dose-dependent manner. Insulin-to-glucose ratio was also increased by EO treatment. Immunostaining of pancreas showed that EO250 increased ß-cell size, but EO500 increased ß-cells number in diabetic rats. EO significantly increased plasma total antioxidants and liver GSH and decreased liver TBARS. EA stimulated glucose-stimulated insulin secretion from isolated islets and decreased glucose intolerance in diabetic rats. CONCLUSION: Ellagic acid in EO exerts anti-diabetic activity through the action on ß-cells of pancreas that stimulates insulin secretion and decreases glucose intolerance.

Imaging trace element distributions in single organelles and subcellular features.

The distributions of chemical elements within cells are of prime importance in a wide range of basic and applied biochemical research. An example is the role of the subcellular Zn distribution in Zn homeostasis in insulin producing pancreatic beta cells and the development of type 2 diabetes mellitus. We combined transmission electron microscopy with micro- and nano-synchrotron X-ray fluorescence to image unequivocally for the first time, to the best of our knowledge, the natural elemental distributions, including those of trace elements, in single organelles and other subcellular features. Detected elements include Cl, K, Ca, Co, Ni, Cu, Zn and Cd (which some cells were supplemented with). Cell samples were prepared by a technique that minimally affects the natural elemental concentrations and distributions, and without using fluorescent indicators. It could likely be applied to all cell types and provide new biochemical insights at the single organelle level not available from organelle population level studies.

17ß-estradiol protects against glucosamine-induced pancreatic ß-cell dysfunction.

OBJECTIVE: Glucosamine (GlcN) is a popular supplement for osteoarthritis in postmenopausal women. Although GlcN possibly induces insulin resistance, the effects of GlcN on ß-cell dysfunction are still obscure. METHODS: In the present study, we investigated changes in insulin production and ß-cell apoptosis in pancreatic islets after GlcN treatment in rats with or without ovariectomy and used MIN-6 cells to investigate the protective effects and molecular mechanisms of 17ß-estradiol (E2) in GlcN-induced ß-cell dysfunction. The rats were divided into four groups: (1) sham operation (SHAM; n = 8); (2) SHAM with 750 mg/kg/day GlcN injected intraperitoneally for 14 days (SHAM + GlcN; n = 10); (3) ovariectomy (OVX; n = 9); and (4) OVX with 750 mg/kg/day GlcN injected intraperitoneally for 14 days (OVX + GlcN; n = 9). RESULTS: Both GlcN and ovariectomy reduced the expression of insulin, determined by the staining intensity of insulin and reverse polymerase chain reaction. GlcN alone also induced ß-cell apoptosis, and this adverse effect was aggravated after ovariectomy. In addition, we found that GlcN decreased calcium influx and insulin secretion by decreasing the protein levels of inwardly rectifying potassium in the ATP-sensitive potassium channel. GlcN decreased the protein levels of endoplasmic reticulum (ER) stress-associated proteins, including C/EBP homologous protein, phospho-protein kinase-like endoplasmic reticulum kinase, phospho-eukaryotic initiation factor 2α, and phospho-c-Jun N-terminal kinase. Finally, GlcN decreased cell viability. E2 counteracted GlcN-mediated attenuation in intracellular calcium concentration, extracellular insulin secretion, protein levels of inwardly rectifying potassium, cell viability, and protein levels of ER stress-associated proteins. ICI182.780 inhibited these beneficial effects of E2. CONCLUSIONS: GlcN impairs insulin secretion of ß-cells by inhibiting Ca influx and enhancing ß-cell apoptosis with increases in ER stress-related proteins, whereas E2 counters these adverse effects of GlcN.

Hispidin produced from Phellinus linteus protects pancreatic beta-cells from damage by hydrogen peroxide.

Phellinus linteus, which is a traditional medicinal mushroom used in Asian countries for the treatment of various diseases, has attracted a lot of attention due to its antioxidant, anti-inflammatory, anti-mutagenicity, and cell-mediated immunity properties in addition to its ability to inhibit tumor growth and metastasis. However, the antidiabetic efficacy of P. linteus has not yet been examined. In this study, hispidin from P. linteus exhibited quenching effects against DPPH radicals, superoxide radicals, and hydrogen peroxide in a dose-dependent manner. Intracellular reactive oxygen species scavenging activity of hispidin was approximately 55% at a concentration of 30 microM. In addition, hispidin was shown to inhibit hydrogen peroxide-induced apoptosis and increased insulin secretion in hydrogen peroxide-treated cells. These combined results indicate that hispidin may act as an antidiabetic and that this property occurs through preventing beta-cells from the toxic action of reactive oxygen species in diabetes.

The effects of cell density and device arrangement on the behavior of macroencapsulated beta-cells.

Over the last several decades, considerable research has focused on the development of cell encapsulation technology to treat a number of diseases, especially type 1 diabetes. One of the key advantages of cell encapsulation is that it permits the use of xenogenic tissue, particularly animal-derived cell lines. This is an attractive idea, because it circumvents the issue of a limited human organ supply. Furthermore, as opposed to whole islets, cell lines have a better proliferative capacity and can easily be amplified in culture to provide an endless supply of uniform cells. We have previously described a macroencapsulation device for the immunoisolation of insulin-secreting 1-cells. The aim of this work was to optimize the viability and insulin secretion of cells encapsulated within this device. Specifically, the effects of cell packing density and device membrane configuration were investigated. The results indicated that cell density plays an important role in the secretory capacity of the cells, with higher cell density leading to increased insulin secretion. Increasing the transport area of the capsule by modifying the membrane configuration also led to an improvement in the insulin output of the device.