Acarbose is widely used as α-glucosidase inhibitor in the treatment of type Ⅱ diabetes. Actinoplanes sp. is used for industrial production of acarbose. As a secondary metabolite, the biosynthesis of acarbose is quite complex. In addition to acarbose, a few acarbose structural analogs are also accumulated in the culture broth of Actinoplanes sp., which are hard to remove. Due to lack of systemic understanding of the biosynthesis and regulation mechanisms of acarbose and its structural analogs, it is difficult to eliminate or reduce the biosynthesis of the structural analogs. Recently, the advances in omics technologies and molecular biology have facilitated the investigations of biosynthesis and regulatory mechanisms of acarbose and its structural analogs in Actinoplanes sp.. The genes involved in the biosynthesis of acarbose and its structural analogs and their regulatory mechanism have been extensively explored by using bioinformatics analysis, genetic manipulation and enzymatic characterization, which is summarized in this review.
Acarbose/metabolism* ; Diabetes Mellitus, Type 2/drug therapy* ; Genetic Techniques ; Humans

BACKGROUNDGlycemic variability, an HbA1c-independent risk factor, has more deleterious effects than sustained hyperglycemia in the development of diabetic complications. This study analyzed the characteristics of glycemic variability in type 2 diabetes mellitus (T2DM) with HbA1c < 6.5% in duration of twice daily premixed insulin treatment and the effect of further treatment with acarbose.

METHODSEighty-six T2DM patients who used premixed insulin analogue (insulin aspart 30) twice daily and had HbA1c < 6.5% and 20 controlled subjects with normal glucose regulation (NGR) were monitored using the continuous glucose monitoring (CGM) system. The mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD) were used for assessing intra-day, inter-day glycemic variability. Hypoglycemia was defined as glucose level < 3.9 mmol/L for at least 15 minutes in CGM. According to reference values of MAGE, T2DM patients were classified into two groups: low-MAGE group with MAGE < 3.4 mmol/L (L-MAGE) and high-MAGE group with MAGE ≥ 3.4 mmol/L (H-MAGE). H-MAGE group received further treatment with acarbose for 2 weeks and was monitored a second time with CGM system.

RESULTSAfter first CGM, L-MAGE group had 41 cases, and H-MAGE group had 45 cases. The MAGE and MODD of T2DM group were all higher than those of subjects with NGR (P < 0.01). Twenty-four percent (n = 11) in H-MAGE group had a total of 13 hypoglycemic events, 10 of the 13 events occurred at night, meanwhile 5% (n = 2) in L-MAGE group had a total of 2 hypoglycemic events, which also occurred at night (hypoglycemic events: 24% vs. 5%, χ(2) = 6.40, P < 0.01). MAGE value was correlated with hypoglycemia value and 2-hour postprandial plasma glucose value (r = -0.32 and 0.26, respectively, P < 0.05). After further acarbose therapy and secondly CGM, MAGE and MODD values in H-MAGE group were all significantly decreased (40%, P < 0.01, and 15%, P < 0.05, respectively), but remained higher than in the subjects with NGR (P < 0.05); 2% (n = 1) had a total of 1 hypoglycemic event, incidence significantly decreased (2% vs. 24%, χ(2) = 9.61, P < 0.01).

CONCLUSIONSCGM system can detect the glycemic variability and asymptomatic hypoglycemic events of T2DM with well-controlled HbA1c in duration of insulin treatment. Combination therapy of premixed insulin twice daily with acarbose can flat glycemic variability and decrease hypoglycemic events.

Acarbose ; administration & dosage ; therapeutic use ; Adult ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; metabolism ; Female ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemic Agents ; therapeutic use ; Insulin ; administration & dosage ; therapeutic use ; Male ; Middle Aged

OBJECTIVETo search alpha-glucosidase inhibitors from Luculia pinciana.

METHODThe alpha-glucosidase inhibitor was isolated by the column chromatographic techniques and the bioassay-guided method in vitro. A combination of MS and NMR spectroscopy was used to identify the chemical structures. The inhibitory kinetic of the isolations was also investigated.

RESULTThe ethyl acetate extract showed strongest inhibitory activity, and five active compounds were isolated and identified as scopletin (1), 5-methoxy-8-hydroxycoumarin (2), lalpha,3beta,24-trihydroxyursolic acid (3), ursolic acid (4) and oleanolic acid (5). The IC50 values of all compounds were lower than that of acarbose. Four of them shown noncompetitive type manner on alpha-glucosidase inhibition except that compound 3 is competitive type manner.

CONCLUSIONCompounds 1-4 as the inhibitors of alpha-glucosidase were reported for the first time.

Acarbose ; pharmacology ; Coumarins ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Glycoside Hydrolase Inhibitors ; Inhibitory Concentration 50 ; Oleanolic Acid ; isolation & purification ; pharmacology ; Plant Extracts ; pharmacology ; Rubiaceae ; chemistry ; Triterpenes ; isolation & purification ; pharmacology ; alpha-Glucosidases ; metabolism

OBJECTIVETo observe the effect of combination therapy of acarbose and Liuwei Nengxiao capsule (LWNXC) in improving senile postprandial hyperglycemia and insulin sensitivity.

METHODSSeventy-four patients with simple postprandial hyperglycemia were divided into the control group and the treated group, 37 in each group, who were treated with acarbose alone and the combination therapy respectively for 1 month, and the changes on 2 hrs postprandial glucose (2 hPG), blood pressure (BP), blood lipid, body mass index (BMI), insulin functional index as well as the adverse reaction of acarbose in the two groups were observed.

RESULTSAfter treatment, the levels of 2 hPG, fasting blood glucose (FBG), BMI, total cholesterol and lowdensity lipoprotein-cholesterol were improved in the treated groups more significantly than those in the control group (P < 0.05 or P < 0.01). Insulin sensitive index (ISI) and insulin resistance were improved in the two group (P < 0.05 or P < 0.01), but the improvement in the treated group was more significant than that in the control group (P < 0.01). Moreover, the adverse reactions were less in the treated group than in the control group.

CONCLUSIONThe combination therapy of acarbose and LWNXC could not only improve the postprandial hyperglycemia, but also markedly increase the insulin sensitivity, and shows obvious improving effect on parameters of blood lipid, BP and BMI. The adverse reaction could be evidently reduced by combined use with LWNXC.

Acarbose ; therapeutic use ; Aged ; Blood Glucose ; metabolism ; Capsules ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glycoside Hydrolase Inhibitors ; Humans ; Hyperglycemia ; drug therapy ; Hypoglycemic Agents ; therapeutic use ; Insulin Resistance ; Lipids ; blood ; Male ; Middle Aged ; Phytotherapy ; Postprandial Period

OBJECTIVETo observe the effect of Yuquan Pill (YP) on proinflammatory cytokines in patients with type 2 diabetes mellitus (DM2).

METHODSNinety patients with DM2 were randomly divided into the treated group and the control group by the ratio of 2:1. Both groups were treated with Glucobay on the base of dietary and exercise therapy for 3 months, with YP, given to the treated group additionally 6 g four times a day. And the changes of proinflammatory cytokines, including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), etc. were observed.

RESULTSThe levels of serum CRP,TNF-alpha and IL-6 significantly lowered after treatment in both groups (P<0.01), and the improvement in the treated group was superior to that in the control group (P<0.01).

CONCLUSIONYP could reduce the levels of the increased proinflammatory cytokines in patients with DM2.

Acarbose ; therapeutic use ; Adult ; Aged ; C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Hypoglycemic Agents ; therapeutic use ; Interleukin-6 ; blood ; Male ; Middle Aged ; Phytotherapy ; Tumor Necrosis Factor-alpha ; blood

BACKGROUND/OBJECTIVES: Recent living condition improvements, changes in dietary habits, and reductions in physical activity are contributing to an increase in metabolic syndrome symptoms including diabetes and obesity. Through such societal developments, humankind is continuously exposed to metabolic diseases such as diabetes, and the number of the victims is increasing. This study investigated Cordyceps militaris water extract (CMW)-induced glucose uptake in HepG2 cells and the effect of CMW treatment on glucose metabolism. MATERIALS/METHODS: Colorimetric assay kits were used to determine the glucokinase (GK) and pyruvate dehydrogenase (PDH) activities, glucose uptake, and glycogen content. Either RT-PCR or western blot analysis was performed for quantitation of glucose transporter 2 (GLUT2), hepatocyte nuclear factor 1 alpha (HNF-1α), phosphatidylinositol 3-kinase (PI3k), protein kinase B (Akt), phosphorylated AMP-activated protein kinase (pAMPK), phosphoenolpyruvate carboxykinase, GK, PDH, and glycogen synthase kinase 3 beta (GSK-3β) expression levels. The α-glucosidase inhibitory activities of acarbose and CMW were evaluated by absorbance measurement. RESULTS: CMW induced glucose uptake in HepG2 cells by increasing GLUT2 through HNF-1α expression stimulation. Glucose in the cells increased the CMW-induced phosphorylation of AMPK. In turn, glycolysis was stimulated, and glyconeogenesis was inhibited. Furthermore, by studying the mechanism of action of PI3k, Akt, and GSK-3β, and measuring glycogen content, the study confirmed that the glucose was stored in the liver as glycogen. Finally, CMW resulted in a higher level of α-glucosidase inhibitory activity than that from acarbose. CONCLUSION: CMW induced the uptake of glucose into HepG2 cells, as well, it induced metabolism of the absorbed glucose. It is concluded that CMW is a candidate or potential use in diabetes prevention and treatment.
Acarbose ; alpha-Glucosidases* ; AMP-Activated Protein Kinases ; Blotting, Western ; Cordyceps* ; Food Habits ; Glucokinase ; Glucose Transport Proteins, Facilitative ; Glucose* ; Glycogen ; Glycogen Synthase Kinase 3 ; Glycolysis ; Hep G2 Cells* ; Hepatocyte Nuclear Factor 1-alpha ; Hypoglycemic Agents ; Liver ; Metabolic Diseases ; Metabolism* ; Motor Activity ; Obesity ; Oxidoreductases ; Phosphatidylinositol 3-Kinase ; Phosphoenolpyruvate ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; Pyruvic Acid ; Social Conditions ; Water*