Eight terpenoids were isolated from the fruits of Amomum villosum by silica gel, Sephadex LH-20, Rp-C_(18), MCI GEL CHP20 P column chromatography, preparative TLC, and HPLC. Their structures were identified by HR-ESI-MS, ~1H and ~(13)C-NMR, IR, UV, [α]_D, and ECD spectroscopic data as kravanhin A 3-O-β-D-glucopyranoside(1), kravanhin B(2), 6-eudesmene-1β,4β-diol(3), oplodiol(4), vicodiol(5),(1R,2S,4R,7S)-vicodiol 9-O-β-D-glucopyranoside(6),(1R,2S,4S,5R)-angelicoidenol 2-O-β-D-glucopyranoside(7), and(1S,2S,4R,6S)-bornane-2,6-diol 2-O-β-D-glucopyranoside(8). Compound 1 was a new compound, and compounds 2-5 were isolated from A. villosum for the first time. Their hypoglycemic activity was tested based on STC-1 cell model and two enzymatic models(GPa and PTP1 B). The results showed that compounds 1, 7, and 8 could stimulate GLP-1 with the secretion rates of 692.8%, 398.6%, and 483.3% at 25.0 μmol·L~(-1), and compound 6 showed inhibitory activity against GPa with an IC_(50) value of 78.6 μmol·L~(-1).
Fruit/chemistry* ; Terpenes/analysis* ; Amomum ; Hypoglycemic Agents/analysis* ; Chromatography, High Pressure Liquid

AIMTo establish a polarographic method of parallel catalytic hydrogen wave for determination of glimepiride.

METHODSThe catalytic wave of glimepiride in the presence of K2S2O8 was used to improve the analytical sensitivity. The rapid determination of glimepiride was done by linear single sweep polarography.

RESULTSThe catalytic hydrogen wave of glimepiride was measured at ca. -1.36 (vs SCE) in 0.09 mol x L(-1) Na2B4O7-KH2PO4 (pH 6.24 +/- 0.1) supporting electrolyte. When 1.0 x 10(-2) mol x L(-1) K2S2O8 was present, the current increased by 25 times, and the peak potentioal was unchanged, producing a more sensitive parallel catalytic hydrogen wave. The peak current of the parallel catalytic hydrogen wave was rectilinear to the glimepiride concentration in the range 1.0 x 10(-7) - 4.2 x 10(-5) mol x L(-1) (r = 0.9990, n = 9). The detection limit was 5.0 x 10(-8) mol x L(-1).

CONCLUSIONThe proposed method could be applied to the determination of glimepiride in pharmaceuticals without preliminary separation.

Catalysis ; Humans ; Hypoglycemic Agents ; analysis ; urine ; Male ; Polarography ; methods ; Potassium Compounds ; analysis ; Sulfates ; analysis ; Sulfonylurea Compounds ; analysis ; urine

OBJECTIVETo develop a HPLC assay for the determination of metformin hydrochloride-related substances.

METHODSThe separation was performed on SHIMADZU VP-ODS (250 4.6 mm, 5 microm) column. The mobile phase of dicyandiamide was composed of methyl alcohol-1 mmol x L(-1) sodium dodecylsulfate in 10 mmol x L(-1) phosphate salt solution (60:40) (pH=5.5). The mobile phase of other related substances was composed of methyl alcohol-1 mmol x L(-1) sodium dodecysulfate in 10 mmol x L(-1) phosphate salt solution (55:45)(pH=5.5). The detection wavelength was 232 nm, and the running speed was 0.8 ml min(-1) at room temperature.

RESULTGood resolution of dicyandiamide and main peak was obtained. The test results were reproducible.

CONCLUSIONThe method is simple, rapid and suitable for the determination of dicyandiamide and other metformin hydrochloride-related substances.

Chromatography, High Pressure Liquid ; Guanidines ; analysis ; Hypoglycemic Agents ; chemistry ; Metformin ; chemistry ; Sensitivity and Specificity ; Tablets

Although various basal-bolus insulin therapy (BBIT) protocols have been used in the clinical environment, safer and more effective BBIT protocols are required for glucose control in hospitalized patients with type 2 diabetes (T2D). Modeling approaches could provide an evaluation environment for developing the optimal BBIT protocol prior to clinical trials at low cost and without risk of danger. In this study, an in-silico model was proposed to evaluate subcutaneous BBIT protocols in hospitalized patients with T2D. The proposed model was validated by comparing the BBIT protocol and sliding-scale insulin therapy (SSIT) protocol. The model was utilized for in-silico trials to compare the protocols of adjusting basal-insulin dose (BBIT1) versus adjusting total-daily-insulin dose (BBIT2). The model was also used to evaluate two different initial total-daily-insulin doses for various levels of renal function. The BBIT outcomes were superior to those of SSIT, which is consistent with earlier studies. BBIT2 also outperformed BBIT1, producing a decreased daily mean glucose level and longer time-in-target-range. Moreover, with a standard dose, the overall daily mean glucose levels reached the target range faster than with a reduced-dose for all degrees of renal function. The in-silico studies demonstrated several significant findings, including that the adjustment of total-daily-insulin dose is more effective than changes to basal-insulin dose alone. This research represents a first step toward the eventual development of an advanced model for evaluating various BBIT protocols.
Blood Glucose/analysis ; Diabetes Mellitus, Type 2/*drug therapy ; Hospitalization ; Humans ; Hypoglycemic Agents/*therapeutic use ; Insulin/*therapeutic use ; Models, Theoretical

Blood Glucose ; China ; Diabetes Mellitus, Type 2/drug therapy* ; Glycated Hemoglobin A/analysis* ; Glycemic Control ; Humans ; Hypoglycemic Agents/therapeutic use*

As one of the important active components of traditional Chinese medicine (TCM), plant origin active proteins have many significant pharmacological functions. According to researches on the plant origin active proteins reported in recent years, pharmacological effects include anti-tumor, immune regulation, anti-oxidant, anti-pathogeny microorganism, anti-thrombus, as well as hypolipidemic and hypoglycemic activities of plant origin were reviewed, respectively. On the other hand, the analytical methods including chromatography, spectroscopy, electrophoresis and mass spectrometry for plant origin proteins analysis were also summarized. The main purpose of this paper is providing a reference for future development and application of plant active proteins.
Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Antioxidants ; pharmacology ; Fibrinolytic Agents ; pharmacology ; Humans ; Hypoglycemic Agents ; pharmacology ; Immunologic Factors ; pharmacology ; Plant Proteins ; analysis ; pharmacology ; Research

OBJECTIVETo establish a reliable platform for screening glucokinase activators (GKAs) in vitro.

METHODSPancreatic glucokinase (PGK) protein expressed in a prokaryotic expression system as a histidine-tagged fusion protein from Homo sapiens was produced. Then, response surface methodology (RSM) was used to optimize the microplate-based GKA screening platform. In the first step of optimization with Plackett-Burman design (PBD), initial pH, reaction time and MgCl2 were found to be important factors affecting the activity ratio of GKA (RO-28-1675) significantly. In the second step, a 2(3) full factorial central composite design (CCD) and RSM were applied to the optimal condition determination of each significant variable. A second-order polynomial was determined by a multiple regression analysis of the experimental data.

RESULTSThe following optimal values for the critical factors were obtained: initial pH 0 (7.0), reaction time-0.63 (13.7 min) and MgCl2 0.11 (2.11 mmol/L) with a predicted value of the maximum activity ratio of 34.1%.

CONCLUSIONUnder the optimal conditions, the practical activity ratio is 34.8%. The determination coefficient (R2) is 0.9442, ensuring adequate credibility of the model. LLAE3, extracted from Folium nelumbinis in our laboratory, has prominently activated effects on PGK.

Analysis of Variance ; Drug Discovery ; methods ; Enzyme Activators ; analysis ; Escherichia coli ; genetics ; Genetic Vectors ; Glucokinase ; metabolism ; Humans ; Hydrogen-Ion Concentration ; Hypoglycemic Agents ; analysis ; Kinetics ; Time Factors

BACKGROUNDDiabetes mellitus has become epidemic in recent years in China. We investigated the prevalence of hyperglycaemia and inadequate glycaemic control among type 2 diabetic inpatients from ten university teaching hospitals in Guangdong Province, China.

METHODSInadequate glycaemic control in diabetic patients was defined as HbA1c = 6.5%. Therapeutic regimens included no-intervention, lifestyle only, oral antiglycemic agents (OA), insulin plus OA (insulin + OA), or insulin only. Antidiabetic managements included monotherapy, double therapy, triple or quadruple therapy.

RESULTSAmong 493 diabetic inpatients with known history, 75% had HbA1c = 6.5%. Inadequate glucose control rates were more frequently seen in patients on insulin + OA regimen (97%) than on OA regimen (71%) (P < 0.001), and more frequent in patients on combination therapy (81% - 96%) than monotherapy (75%) (P < 0.05). Patients on insulin differed significantly from patients on OA by mean HbA1c, glycemic control rate, diabetes duration, microvascular complications, and BMI (P < 0.01).

CONCLUSIONSThis study showed that glycaemic control of type 2 diabetic patients deteriorated for patients who received insulin and initiation time of insulin was usually delayed. It is up to clinicians to move from the traditional stepwise therapy to a more active and early combination antidiabetic therapy to provide better glucose control.

Aged ; China ; epidemiology ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Female ; Glycated Hemoglobin A ; analysis ; Humans ; Hyperglycemia ; epidemiology ; Hypoglycemic Agents ; administration & dosage ; Inpatients ; Male ; Middle Aged

Based on the SAR of glinide agents, mitiglinide has been modified to study the SAR of glinides. a-Benzylsuccinic acid derivatives which were designed and synthesized in order to find some more hypoglycemic active agents and further investigate the SAR of this class of compounds. From ethyl succinate and substituded benzaldehydes, twelve new target compounds were synthesized by codensation, hydrolysis, anhydridization, amidation and hydrogenization reactions, and their hypoglycemic activity were evaluated with glucose oxidase kit. All the compounds were characterized by elemental analysis, IR, 1H NMR and ESI-MS. The preliminary pharmacological test showed that the compounds have good hypoglycemic activity, especially 6c, 6e and 6g, 6e showed the same hypoglycemic potency as nateglinide.
Animals ; Blood Glucose ; analysis ; Female ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Male ; Mice ; Random Allocation ; Structure-Activity Relationship ; Succinates ; chemical synthesis ; chemistry ; pharmacology

An HPLC-UV method has been developed for the determination of valibose, miglitol, voglibose and acarbose, the four anti-diabetic drugs. The separation was accomplished successfully by using reversed phase chromatography (Prevail carbohydrate column, 250 mm x 4.6 mm, 5 microm) with a gradient acetonitrile-phosphate buffer solution (pH 8.0) at a wavelength of 210 nm. Furthermore, the method of a high-performance liquid chromatography coupled with ESI-MS in positive ionization mode has been established. These two methods were successfully applied to the assay and qualitative detection of four alpha-glucosidase inhibitors in the potential counterfeit anti-diabetic drugs.
1-Deoxynojirimycin ; analogs & derivatives ; analysis ; Acarbose ; analysis ; Chromatography, High Pressure Liquid ; methods ; Chromatography, Reverse-Phase ; Glycoside Hydrolase Inhibitors ; Hypoglycemic Agents ; chemistry ; Inositol ; analogs & derivatives ; analysis ; Spectrometry, Mass, Electrospray Ionization ; methods ; Spectrophotometry, Ultraviolet ; alpha-Glucosidases ; analysis