2-(n-(7-nitrobenz-2-oxa-1-3-diazol-4-yl)amino)-2-deoxyglucose and Diabetes-Mellitus--Type-2

Gymnema sylvestre (Retz.) R.Br. ex Sm. (Asclepiadaceae) is a well-known Ayurvedic anti-sweet plant for the treatment of type 2 diabetes mellitus. Although it was previously proposed that G. sylvestre exhibits chemical variation based on geography, most research on G. sylvestre has used material originating from India. Morphological and anatomical descriptions, ITS1-5.8S-ITS2 DNA sequencing, and acid hydrolysis analyses showed that G. sylvestre samples from Vietnam are distinguishable from those of Indian origin and thus suggest a dissimilarity among G. sylvestre samples with different geographic distributions. An LC-MS-guided strategy targeting 3β-glucuronide oleane-triterpenes in the Vietnamese G. sylvestre variety led to the isolation of four known compounds and nine previously undescribed compounds, named gymnemosides ND1-ND9. None of the isolated compounds were reported in the Indian sample, further supporting the geo-diversity of G. sylvestre. Three compounds, gymnemosides ND7-9, exerted significant stimulatory effects on the uptake of 2-NBDG in 3T3-L1 adipocyte cells and thus have potential as lead molecules for anti-diabetes agents.

Topics: 4-Chloro-7-nitrobenzofurazan; Deoxyglucose; Diabetes Mellitus, Type 2; Gymnema sylvestre; Hypoglycemic Agents; India; Oleanolic Acid; Plant Extracts; Plant Leaves; Saponins; Vietnam

In this paper, we investigated the effects of Coptis chinensis polysaccharide (CCP) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. CCP was prepared by extraction from Coptis chinensis and oral given to the mice. C57BL/6J mice in each of the 5 groups (eight mice per group) were given either the normal diet (ND) (D12450B, 10% kcal% fat; Research diet, New Brunswick, NJ, USA), HFD (D12451, 45% kcal% fat; Research diet, New Brunswick, NJ, USA), or HFD with CCP of differing hardness (500, 1000, and 2000ppm) for 20 weeks. Mice given an HFD with CCP showed lowered fasting plasma glucose levels compared to HFD-fed mice. Oral and intraperitoneal glucose tolerance tests showed that CCP improves impaired glucose tolerance in HFD-fed mice. Histopathological evaluation of the pancreas showed that CCP recovers the size of the pancreatic islets of Langerhans, and increases the secretion of insulin and glucagon in HFD-fed mice. Quantitative reverse transcription polymerase chain reaction results revealed that the expression of hepatic genes involved in glucogenesis, glycogenolysis and glucose oxidation were suppressed, while those in glucose uptake, β-oxidation, and glucose oxidation in muscle were increased in mice fed HFD with CCP. CCP increased AMP-dependent kinase (AMPK) phosphorylation in 3T3-L1 pre- and mature adipocytes and improved impaired AMPK phosphorylation in the muscles and livers of HFD-induced diabetic mice. CCP stimulated phosphoinositol-3-kinase and AMPK pathway-mediated glucose uptake in 3T3-L1 adipocytes. Taken together, these results suggest that CCP has potential as an anti-diabetic agent, given its ability to suppress hyperglycemia and improve glucose intolerance by increasing glucose uptake.

Topics: 3T3-L1 Cells; 4-Chloro-7-nitrobenzofurazan; Adenylate Kinase; Adipocytes; Adipokines; Animals; Blood Glucose; Body Weight; Coptis; Cytokines; Deoxyglucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Fasting; Feeding Behavior; Gene Expression Regulation; Gluconeogenesis; Insulin; Lipids; Male; Mice; Mice, Inbred C57BL; Phosphorylation; Polysaccharides

This study investigated the effect of a β-x200B;hydroxyphosphonate analog of ʟ-carnitine (L-CA) (CAS number: 1220955-x200B;20-3, Component: 1221068-91-2, C12H29NO4PI), (3-Hexanaminium, 1-(dimethoxyphosphinyl)-2-hydroxy-N,N,N,5-x200B;tetramethy-iodide (1:1), (2R, 3S)) on parameters related with type-2 diabetes in an in vitro model. Nontoxic concentrations of L-CA were assayed and compared to commercial ʟ-carnitine effects. L-CA did not affect adipogenesis in normal cells, but an increment of TG accumulation was observed on insulin-resistant adipocytes (80%) when compared with resistant control. L-CA also stimulated glucose analog 2-NBDG uptakes on insulin-resistant adipocytes in a similar way as insulin when compared to insulin-resistant cells. Our results show that the L-CA promoted insulin-like responses on insulin-resistant adipocytes without appreciable pro-adipogenic effect in sensitive adipocytes.

Topics: 3T3-L1 Cells; 4-Chloro-7-nitrobenzofurazan; Adipocytes; Adipogenesis; Animals; Carnitine; Cell Differentiation; Deoxyglucose; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Insulin Resistance; Mice

Alarin, a regulatory peptide, belongs to the galanin family and plays the same regulatory roles as galanin in orexigenic activity and energy metabolism. Our previous studies had found that galanin might facilitate insulin sensitivity via activation of its central receptors. To date, little is known about whether central alarin may exert similar effects on insulin sensitivity. In order to investigate this, alarin and its specific antagonist, alarin 6-25Cys, were administered into the cerebral ventricles of type 2 diabetic rats (T2DR) to evaluate the changes in insulin resistance. The results indicated that central treatment with alarin significantly increased the body weight of animals, the 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake, the plasma adiponectin levels, the glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, the vesicle-associated membrane protein 2 as well as glucose transporter 4 (GLUT4 (SLC2A4)) protein and mRNA levels, and the ratios of GLUT4 contents in plasma membranes to total cell membranes in adipocytes, but reduced blood glucose and plasma retinol-binding protein 4 levels. These effects of alarin may be inhibited by pretreatment with alarin 6-25Cys. The above-mentioned results suggest that the central alarin projective system may facilitate insulin sensitivity and glucose uptake via the increase in GLUT4 content and GLUT4 translocation from intracellular pools to plasma membranes in T2DR.

Topics: 4-Chloro-7-nitrobenzofurazan; Adipocytes; Adiponectin; Animals; Blood Glucose; Blotting, Western; Body Weight; Cell Membrane; Deoxyglucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Galanin-Like Peptide; Gene Expression; Glucose Transporter Type 4; Injections, Intraventricular; Insulin Resistance; Male; Peptide Fragments; Protein Transport; Rats, Wistar; Retinol-Binding Proteins, Plasma; Reverse Transcriptase Polymerase Chain Reaction; Vesicle-Associated Membrane Protein 2

A novel α-glucosidase inhibitor, vomifoliol 9-O-α-arabinofuranosyl (1→6)-β-D-glucopyranoside, was isolated for the first time from leaves of Diospyros Kaki and its bioactivity analyzed. This inhibitor exhibited strong anti-α-glucosidase activity with an IC50 value of 170.62nM and stimulated a dose-dependent increase in the uptake of a fluorescent d-glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG), in HepG2 cells at a rate higher than that of insulin controls. It was also found to be associated with adipocyte differentiation and moderate increases in 2-NBDG uptake by 3T3-L1 cells. These findings suggest that vomifoliol 9-O-α-arabinofuranosyl (1→6)-β-D-glucopyranoside could augment peripheral glucose as an insulin-sensitizing agent against Type 2 diabetes mellitus.

Topics: 3T3-L1 Cells; 4-Chloro-7-nitrobenzofurazan; Animals; Butanols; Cell Differentiation; Cyclohexanols; Cyclohexanones; Deoxyglucose; Diabetes Mellitus, Type 2; Diospyros; Disaccharides; Dose-Response Relationship, Drug; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Hep G2 Cells; Humans; Hypoglycemic Agents; Mice

Cecropia obtusifolia Bertol (Cecropiaceae) is a plant extensively used for the empirical treatment of type 2 diabetes in México. Although some of its hypoglycemic principles have been described, their mechanisms of action remain unclear.. To investigate the anti-diabetic mechanisms of Cecropia obtusifolia aqueous extract (CAE) and its active compound chlorogenic acid (CGA).. Non-toxic concentrations of CAE and CGA were assayed on the adipogenesis and 2-NBDglucose uptake in 3T3-F442A murine adipocytes.. Added to adipogenic medium, CAE 70 microg/ml induced a modest increment (20%) in 3T3 adipogenesis whereas CGA did not affect adipogenesis at any of the tested concentrations (0.1-100 microM). Both preparations stimulated 2-NBDG uptake in adipocytes by 51% (CAE) and 176% (CGA) in the absence of insulin, and by 174% (CAE) and 404% (CGA) in the presence of the hormone. CAE and CGA also stimulated the 2-NBDG uptake in insulin-resistant 3T3 adipocytes by 35% and 141%, respectively, compared with the incorporation shown by insulin-sensitive adipocytes stimulated by the hormone. The potency of CGA to stimulate 2-NBDG uptake was comparable to the anti-diabetic drug rosiglitazone.. Cecropia obtusifolia and CGA exert their anti-diabetic effects stimulating glucose uptake in both insulin-sensitive and insulin-resistant adipocytes without appreciable pro-adipogenic effects.

Topics: 4-Chloro-7-nitrobenzofurazan; Adipocytes; Adipogenesis; Analysis of Variance; Animals; Cecropia Plant; Cell Line; Chlorogenic Acid; Chromatography, High Pressure Liquid; Deoxyglucose; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Insulin; Insulin Resistance; Mexico; Mice; Phytotherapy; Plant Extracts; Plant Structures