Dapagliflozin improves skeletal muscle insulin sensitivity through SIRT1 activation induced by nutrient deprivation state.

Lipid peroxidation and mitochondrial damage impair insulin sensitivity in skeletal muscle. Sirtuin-1 (SIRT1) protects mitochondria and activates under energy restriction. Dapagliflozin (Dapa) is an antihyperglycaemic agent that belongs to the sodium-glucose cotransporter-2 (SGLT2) inhibitors. Evidence shows that Dapa can induce nutrient deprivation effects, providing additional metabolic benefits. This study investigates whether Dapa can trigger nutrient deprivation to activate SIRT1 and enhance insulin sensitivity in skeletal muscle. We treated diet-induced obese (DIO) mice with Dapa and measured metabolic parameters, lipid accumulation, oxidative stress, mitochondrial function, and glucose utilization in skeletal muscle. ß-hydroxybutyric acid (ß-HB) was intervened in C2C12 myotubes. The role of SIRT1 was verified by RNA interference. We found that Dapa treatment induced nutrient deprivation state and reduced lipid deposition and oxidative stress, improved mitochondrial function and glucose tolerance in skeletal muscle. The same positive effects were observed after ß-HB intervening for C2C12 myotubes, and the promoting effects on glucose utilization were diminished by SIRT1 RNA interference. Thus, Dapa promotes a nutrient deprivation state and enhances skeletal muscle insulin sensitivity via SIRT1 activation. In this study, we identified a novel hypoglycemic mechanism of Dapa and the potential mechanistic targets.

Berberine Slows the Progression of Prediabetes to Diabetes in Zucker Diabetic Fatty Rats by Enhancing Intestinal Secretion of Glucagon-Like Peptide-2 and Improving the Gut Microbiota.

Background: Berberine is a plant alkaloid that has multiple beneficial effects against intestine inflammation. In our previous study, we have found that berberine also possesses an antidiabetic effect. However, whether berberine is useful in the prevention of type 2 diabetes mellitus (T2DM) through its effect on intestine endocrine function and gut microbiota is unclear. Aim: To investigate the effects of berberine in the prevention of T2DM, as well as its effects on intestine GLP-2 secretion and gut microbiota in ZDF rats. Methods: Twenty Zucker Diabetic Fatty (ZDF) rats were fed a high-energy diet until they exhibited impaired glucose tolerance (IGT). The rats were then divided into two groups to receive berberine (100 mg/kg/d; berberine group) or vehicle (IGT group) by gavage for 3 weeks. Five Zucker Lean (ZL) rats were used as controls. Fasting blood glucose (FBG) was measured, an oral glucose tolerance test was performed, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated. Intestinal expression of TLR-4, NF-κB, TNF-α, mucin, zona occludens-1 (ZO-1) and occludin were assessed (immunohistochemistry). Plasma levels and glutamine-induced intestinal secretion of glucagon-like peptide-1 (GLP-1) and GLP-2 were measured (enzyme-linked immunosorbent assay). The plasma lipopolysaccharide (LPS) level was measured. Fecal DNA extraction, pyrosequencing, and bioinformatics analysis were performed. Results: After 3 weeks of intervention, diabetes developed in all rats in the IGT group, but only 30% of rats in the berberine group. Treatment with berberine was associated with reductions in food intake, FBG level, insulin resistance, and plasma LPS level, as well as increases in fasting plasma GLP-2 level and glutamine-induced intestinal GLP-2 secretion. Berberine could increase the goblet cell number and villi length, and also reverse the suppressed expressions of mucin, occludin, ZO-1 and the upregulated expressions of TLR-4, NF-κB and TNF-α induced in IGT rats (P<0.05). Berberine also improved the structure of the gut microbiota and restored species diversity. Conclusion: Berberine may slow the progression of prediabetes to T2DM in ZDF rats by improving GLP-2 secretion, intestinal permeability, and the structure of the gut microbiota.

Photothermal-Induced Electrochemical Interfacial Region Regulation Enables Signal Amplification for Dual-Mode Detection of Ovarian Cancer Biomarkers.

Detection sensitivity of an electrochemical immunosensor mainly depends on the accessible distance toward the sensing interface; regulating the electrochemical interfacial region thereon is an effective strategy for signal amplification. Herein, a photothermal-regulated sensing interface was designed based on a near-infrared (NIR)-responsive hydrogel probe for ultrasensitive detection of human epididymis protein 4 (HE4). Silver nanoparticle-deposited graphene oxide nanosheet (AgNPs@GO) hybrids as electrochemical signal tags and a photothermal transducer, which were encapsulated in the poly(N-isopropylacrylamide) (pNIPAM) hydrogel, were used to develop the NIR-responsive GO@AgNPs-pNIPAM hydrogel probe. Under NIR light irradiation, the excellent photothermal effect of AgNPs@GO hybrids not only rapidly converted NIR light into heat for temperature readout but also triggered the shrinkage behavior of the hydrogel for electrochemical signal amplification. Compared with the conventional sandwich immunoassay, the shrinkage behavior of the hydrogel signal probe endowed itself with interface regulation capability to improve the electrochemical reaction efficiency; on the basis of ensuring the extended outer Helmholtz plane (OHP) region, the proposed photothermal-induced interface regulation also shortened the OHP, leading to higher sensitivity. Moreover, the obtained dual-mode signals provided satisfactory accuracy for the detection of tumor markers. Therefore, this detection scheme provided an opportunity for the broad applications of the photothermal effect in clinical diagnosis.

Dual-readout proximity hybridization-regulated and photothermally amplified protein analysis based on MXene nanosheets.

Herein, an ingenious dual-readout sensing platform based on a proximity hybridization-regulated strategy is proposed for protein detection. For the first time, Ti3C2 MXene@thionine composites (MXene@Thi) with an excellent photothermal effect not only acted as an amplifier to enhance the electrochemical signal, but were also used as a converter to achieve the temperature readout.

Electrochemical Detection of Hydrogen Peroxide by Inhibiting the p-Benzenediboronic Acid-Triggered Assembly of Citrate-Capped Au/Ag Nanoparticles on Electrode Surface.

Metal nanoparticles (NPs) possess unique physicochemical attributes for creating effective recognition and transduction processes in chem/bio-sensing. In this work, we suggested that citrate-capped Au/Ag NPs could be used as the reporters for the design of hydrogen peroxide (H2O2) sensors with a simple manipulation principle and an easy detection procedure. Specifically, p-benzenediboronic acid (BDBA) induced the aggregation of citrate-capped Au NPs through the cross-linking reaction between citrate and boronic acid of BDBA in solution. By modifying the electrode with a boronic acid derivative, the BDBA-induced assembly of Au NPs was achieved on the electrode surface. This led to a significant decrease in the electron transfer resistance due to the unique conductive ability of Au NPs. However, when the boronate group on the electrode surface was oxidized into its phenol format, the assembly of Au NPs on the electrode surface was not achieved. As a result, a higher electron transfer resistance was observed. The process could be monitored by electrochemical impedance technique. Furthermore, when Ag NPs were used instead of Au NPs in this design, the H2O2 concentration could be determined by measuring the linear-sweep voltammetry (LSV) current through the solid-state Ag/AgCl reaction of Ag NPs. The results indicated that NP-based colorimetric assays could be developed into more sensitive electrochemical analysis.

Effects of metformin and sitagliptin on glycolipid metabolism in type 2 diabetic rats on different diets.

INTRODUCTION: The aim of the study was to investigate the effects of metformin and sitagliptin on glycolipid metabolism in type 2 diabetes after different diets. MATERIAL AND METHODS: Seventy Male Sprague Dawley rats were fed with a high fat diet followed by streptozotocin treatment to induce type 2 diabetes. Then all rats were randomly divided into a control group, a metformin group (200 mg/kg), and a sitagliptin group (10 mg/kg). Each group was further divided into 4 groups receiving one load of high carbohydrate diet (45% glucose, 4.5 ml/kg), high fat diet (20% lipid emulsion, 4.5 ml/kg), high protein diet (20% whey protein, 10 ml/kg) or mixed meal, respectively. The caloric densities were all 33 kJ/kg. Postprandial blood glucose (P2BG), triglyceride (TG), glucagon-like peptide-1 (GLP-1), glucagon and insulin levels were measured. RESULTS: In the high carbohydrate group, sitagliptin was more efficient in lowering P2BG compared with metformin (p < 0.05). In the high-fat group, metformin was more powerful in lowering TG (p < 0.05) and P2BG (p < 0.05) levels because of its improvement of insulin sensitivity. In the high protein diet group, metformin did not reduce the P2BG level (p > 0.05), although it did reduce the TG level (p < 0.05). In the mixed diet group, metformin was more efficient in lowering P2BG (p < 0.05) but had a similar effect on TG (p > 0.05) compared with sitagliptin. CONCLUSIONS: In the type 2 diabetic model, metformin and sitagliptin have different effects on glycolipid metabolism after different diets. If it is proved in type 2 diabetic patients, then different medicines may be recommended according to different diets in order to improve glycolipid metabolism.

Glucagon secretion is increased in patients with Type 2 diabetic nephropathy.

AIMS: Currently little is known about the relationship between renal function, albuminuria and glucagon; we analyzed the secretion of glucagon (GLA) and C-peptide in Type 2 diabetic patients with different degrees of nephropathy. METHODS: 357 patients with Type 2 diabetes including 119 cases without nephropathy and 238 cases with nephropathy were divided into four groups according to the stages of diabetic nephropathy. Patients with diabetic nephropathy were further classified according to the level of estimated glomerular filtration rate (eGFR). OGTT and insulin, C-peptide, glucagon releasing tests were performed in all patients. Characteristics of glucagon and C-peptide secretion in different groups were compared. Glucagon/glucose ratio (GLA/GLU) and glucagon/insulin ratio (GLA/INS) were used to represent the inhibition of glucose or insulin on glucagon secretion, respectively. RESULTS: With the progress of diabetic nephropathy, glucagon level increased significantly; the glucagon peak after glucose load delayed from 60 min to 120 min, whereas C-peptide level decreased significantly. Related factors analysis suggested that glucagon was independently correlated with eGFR. Further analysis showed that glucagon level was higher in group with eGFR<60 ml/min compared with that in group with eGFR≥60 ml/min. In addition, both GLA/INS and GLA/GLU were higher in group with eGFR<60 ml/min compared with those in group with eGFR≥60 ml/min. CONCLUSIONS: Patients with Type 2 diabetic nephropathy have worsened islet alpha and beta cell function. Therefore medications based on the regulation of glucagon secretion may improve glycemic control and also be beneficial for delaying the progress of diabetic nephropathy.

Tumor FOXP3 represses the expression of long noncoding RNA 7SL.

The long noncoding RNA 7SL was over-expressed in tumor cells to promote cell growth through repressing translation of P53. However, the regulatory mechanism of 7SL remains to be defined. FOXP3 was identified as a suppressor in several tumors in addition to be a marker of regulatory T cells. In this study, we detected that over-expression of FOXP3 repressed the transcription of 7SL RNA and contributed to inhibiting tumor growth. Knock down of FOXP3 in MCF-10A normal mammary breast cells up-regulated the transcription of 7SL RNA. Chromatin Immuno-precipitation (ChIP) analysis showed that FOXP3 directly bound to the Forkhead/HNF-3 domain DNA binding sites (-789 to -795) relative to the transcription start site. Meanwhile, Luciferase analysis showed that FOXP3 repressed the full-length 7SL promoter activity, but this suppressive effect was reversed after mutation of the FOXP3 binding site. Further studies showed that FOXP3 promoted the expression of P53 at translational levels through repressing 7SL RNA. In conclusion, this study suggests that 7SL RNA is a direct target of FOXP3 and may be involved in the formation of FOXP3/P53 feedback loop.

[Association between retinopathy and sleep disorder in patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the association between retinopathy and sleep disorder in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 440 patients with T2DM treated from July 2011 to July 2013 in Metabolic Disease Hospital of Tianjin Medical University were divided into 2 groups according to Pittsburgh Sleep Quality Index: non-sleep disorder group (258 cases) and sleep disorder group (182 cases). Biochemical parameters including hepatorenal function, blood lipids, glycosylated hemoglobin (HbA1c), fructosamine and hemorrheology were detected. Oral glucose tolerance test, insulin releasing test and glucagon releasing test were performed to detect the inteR-group differences of α-cell and ß-cell function after fasting and glucose-load management. The logistic regression analysis was performed to identify the factors relevant to retinopathy. RESULTS: The ratio of retinopathy was 42.9% in sleep disorder group, which was higher compared to those in non-sleep disorder group (32.6%), P=0.027. The levels of fasting plasma glucose, postprandial blood glucose, HbA1c, fructosamine, systolic blood pressure, diastolic blood pressure and the indicators of hemorrheology (plasma viscosity, erythrocyte aggregation index, erythrocyte rigidity index, fibrinogen) were significantly higher in patients with sleep disorder compared to those without sleep disorder, while the erythrocyte defomation index was significantly lower in sleep disorder group (all P<0.05). The levels of glucagon and glucagon/insulin ratio at each time point as well as area under curve of glucagon were significantly higher in sleep disorder group (all P<0.05). The levels of fasting insulin, homeostasis model assessment for insulin resistance index (HOMA-IR) and area under curve of insulin were significantly higher in patients with sleep disorder compared to those without sleep disorder, while insulin sensitivity index was lower in patients with sleep disorder (all P<0.05). Logistic regression analysis showed that retinopathy was positively related to HbA1c (OR: 1.744-3.249), fibrinogen (OR: 1.687-2.998), systolic blood pressure (OR: 1.152-2.013), HOMA-IR (OR: 1.006-1.389) and sleep disorder (OR: 1.144-2.426), and negatively related to insulin sensitivity index (OR: 0.107-0.784) (all P<0.05). CONCLUSION: Sleep disorders may be associated with retinopathy through multiple mechanisms in patients with T2DM.

[Association between sleep disorder and osteoporosis in elderly female patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the association between sleep disorder and osteoporosis in elderly female patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 536 elderly female T2DM patients from July 2011 to July 2014 were divided into two groups of patients without sleep disorder and those with sleep disorder based upon the Pittsburgh Sleep Quality Index. The bone mineral density of femoral neck, Wards triangle, greater trochanter and lumbar spines (L2-L4) were measured by dual-energy X-ray absorptiometry. Biochemical indicators were detected in two groups. Oral glucose tolerance and insulin releasing tests were performed. We compared the differences of bone mineral density and ß-cell function after fasting and glucose-load. The logistic regression analyses were performed between sleep disorder and osteoporosis and other indicators. RESULTS: The levels of high sensitivity C-reactive protein (hs-CRP), HbA1c, cortisol (COR), adrenocorticotropic hormone (ACTH), fasting insulin (FINS) and homeostasis model assessment-estimated insulin resistance (HOMA-IR) were significantly higher in patients with sleep disorder compared to those without sleep disorder [(3.5 ± 1.1) vs (2.6 ± 0.9) mg/L, (8.0 ± 1.9)% vs (7.3 ± 1.6)%, (512 ± 88) vs (436 ± 76) nmol/L, (6.4 ± 2.3) vs (5.1 ± 2.0) pmol/L, (13.4 ± 4.3) vs (12.4 ± 4.0) mU/L, 4.7 ± 0.8 vs 3.8 ± 0.8, all P < 0.05]. Insulin sensitivity index (ISI) was lower in patients with sleep disorder than that in patients without sleep disorder (-4.2 ± 0.5 vs -4.0 ± 0.4, P < 0.05). The bone mineral density of femoral neck, Wards triangle, greater trochanter and lumbar spines (L2-L4) were significantly lower and the prevalence rate of osteoporosis was significantly higher in patients with sleep disorder compared to those in patients without sleep disorder (all P < 0.05). Logistic regression analysis showed that sleep disorder was positively correlated with HOMA-IR, HbA1c, COR and ACTH (all P < 0.05) and negatively with ISI (P < 0.05). Logistic regression analysis showed that osteoporosis was positively correlated with postmenopausal duration, HbA1c, COR, ACTH and sleep disorder (all P < 0.05) and negatively with ISI (P < 0.05). CONCLUSION: Sleep disorder causes osteoporosis through various mechanisms in elderly female T2DM patients. Improving sleep disorder may help to reduce the prevalence of osteoporosis.

RNA-binding residues prediction using structural features.

BACKGROUND: RNA-protein complexes play an essential role in many biological processes. To explore potential functions of RNA-protein complexes, it's important to identify RNA-binding residues in proteins. RESULTS: In this work, we propose a set of new structural features for RNA-binding residue prediction. A set of template patches are first extracted from RNA-binding interfaces. To construct structural features for a residue, we compare its surrounding patches with each template patch and use the accumulated distances as its structural features. These new features provide sufficient structural information of surrounding surface of a residue and they can be used to measure the structural similarity between the surface surrounding two residues. The new structural features, together with other sequence features, are used to predict RNA-binding residues using ensemble learning technique. CONCLUSIONS: The experimental results reveal the effectiveness of the proposed structural features. In addition, the clustering results on template patches exhibit distinct structural patterns of RNA-binding sites, although the sequences of template patches in the same cluster are not conserved. We speculate that RNAs may have structure preferences when binding with proteins.

[Association between sleep disorders and dawn phenomenon in patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the association between sleep disorders and dawn phenomenon in patients with type 2 diabetes mellitus (T2DM). METHODS: From July 2011 to July 2014 at Metabolic Disease Hospital, Tianjin Medical University, 316 T2DM patients on continuous glucose monitoring were divided into two groups according to the Pittsburgh Sleep Quality Index, i.e. those without sleep disorders (n = 186) and those with sleep disorders (n = 130). Biochemical parameters including hepatorenal functions, blood lipids, glycosylated hemoglobin (HbA1c) and fructosamine were detected. Oral glucose tolerance test, insulin releasing test and glucagon releasing test were performed to detect the inter-group differences of glucose concentration and α-cell and ß-cell functions after fasting and glucose loading. And the correlation and regression analyses were performed between sleep disorders and other parameters. RESULTS: The level of HbA1c, fructosamine, increment of fasting glucose and nocturnal nadir glucose, glucose increment before and after breakfast, 24 h mean glucose, fasting insulin, homeostasis model assessment of insulin resistance index (HOMA-IR) and area under curve of insulin were significantly higher in patients with sleep disorders than those without sleep disorders (8.2% ± 2.0% vs 7.4% ± 1.7%, (0.33 ± 0.10) vs (0.29 ± 0.07) mmol/L, (1.511 ± 0.294) vs (0.889 ± 0.233) mmol/L, (2.144 ± 0.400) vs (1.522 ± 0.378) mmol/L, (9.917 ± 1.800) vs (8.694 ± 1.622) mmol/L, (13.49 ± 4.68) vs (12.16 ± 4.56) mU/L, 4.98 ± 0.90 vs 3.82 ± 0.82, (8.47 ± 0.59) vs (8.25 ± 0.54), all P < 0.05). Insulin sensitivity index was lower in patients with sleep disorders than that in those without sleep disorders (-4.28 ± 0.62 vs -4.03 ± 0.52, P < 0.05). The level of glucagon at each timepoint and area-under-curve of glucagon were significantly higher in patients with sleep disorders than those without sleep disorders. The levels of 0, 30, 180 min glucagon/insulin ratio and glucagon/glucose ratio were significantly higher in patients with sleep disorders (all P < 0.05). Sleep disorder was positively correlated with HOMA-IR, glucagon/insulin ratio, increment of fasting glucose and nocturnal nadir glucose and dawn phenomenon (all P < 0.05). Yet there was a negative correlation with insulin sensitivity index (P < 0.05). CONCLUSIONS: Sleep disorders are associated with dawn phenomenon. And improving sleep disorder helps to improve the dawn phenomenon and optimize overall glycemic control.

Relationship between circadian blood pressure variability and function of islet α and ß cell in type 2 diabetes with dyssomnia.

AIMS: To investigate the relationship between circadian blood pressure (BP) variability and function of islet α and ß cell in type 2 diabetes (T2D) with dyssomnia. METHODS: Patients with T2D were divided into dyssomnia group and non-dyssomnia group by PSQI. OGTT, insulin and glucagon-releasing test were tested, and ambulatory BP was monitored for 24 hours to compare two groups with α and ß cell, circadian BP variability and fasting and post-meal BP variability. The correlation and regression analysis were made between PSQI and other indicators. RESULTS: In dyssomnia group, ① Glucagon, glucagon/insulin ratio and AUCG were significantly higher (P < 0.05). ② Fasting insulin (13.32 ± 4.54 mIU/L), AUCI (8.51 ± 0.54) and HOMA-IR (4.62 ± 1.11) were high (P < 0.05). But ISI (-4.27 ± 0.77) was low (P < 0.05). ③ Mean 24-hour and nighttime SBP and DBP, as well as their standard deviations and coefficients of variation, were all higher in the dyssomnia group (P < 0.05). Multiple stepwise regression analysis showed that PSQI score was positively related to AUCG, HOMA-IR, nighttime SBP, and negatively related to ISI and nocturnal BP fall (P < 0.05). CONCLUSION: Dyssomnia may cause abnormal circadian BP variability through various mechanisms. Improving dyssomnia can help to better function the islet α and ß cell and restore normal circadian BP variability.

Association between eNOS 4b/a polymorphism and the risk of diabetic retinopathy in type 2 diabetes mellitus: a meta-analysis.

Many studies have assessed the association between eNOS-4b/a polymorphism and the risk of diabetic retinopathy (DR) among type 2 diabetic subjects. However, the results are inconsistent. In order to derive a more precise estimation of the association, a meta-analysis was conducted. Fifteen studies with 3, 183 cases and 3, 410 controls were enrolled by searching the databases of Pubmed, Embase, China National Knowledge Infrastructure (CNKI), and Chinese Wanfang Database. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The main analysis indicated no significant association between eNOS-4b/a polymorphism and the risk of DR in overall population [allelic model: OR = 0.94 (0.79-1.11); additive model: OR = 0.91 (0.73-1.14); recessive model: OR = 1.01 (0.81-1.25); dominant model: OR = 0.91 (0.75-1.09)]. Subgroup analysis by ethnicity also indicated no significant association. In conclusion, the current meta-analysis did not observe any association between the polymorphism of eNOS 4b/a and the risk of DR among type 2 diabetic subjects. However, larger well-designed studies are required to confirm this finding.

Endothelial nitric oxide synthase (eNOS) 4b/a polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus: A meta-analysis.

Many studies have accessed the association between eNOS-4b/a polymorphism and the risk of diabetic nephropathy (DN) among type 2 diabetic subjects. However, the results are conflicting and inconclusive. The aim of current meta-analysis was to more precisely estimate the relationship. Pubmed, Embase, the China National Knowledge Infrastructure and the Wanfang Database were searched for articles published up to May 26th, 2013 that addressed eNOS-4b/a polymorphism and the risk of DN among type 2 diabetic subjects. 18 studies were included in this meta-analysis. eNOS-4b/a polymorphisms were associated with an overall significantly increased risk of DN (allele model: OR = 1.44, 95% CI = 1.14-1.82; additive model: OR = 2.03, 95% CI = 1.14-3.62; dominant model: OR = 1.34, 95% CI = 1.07-1.68; recessive model: OR = 2.01, 95% CI = 1.12-3.61). Subgroup analysis revealed a significant association between the eNOS-4b/a polymorphism and DN in Asian population, especially in Chinese population, but not in non Asian populations. Our meta-analysis supported an association between the 4b/a polymorphism of eNOS gene and increased risk of DN in type 2 diabetes among Asians, especially in Chinese population.

Effects of 24-week treatment with acarbose on glucagon-like peptide 1 in newly diagnosed type 2 diabetic patients: a preliminary report.

BACKGROUND: Treatment with the alpha-glucosidase inhibitor (AGI) acarbose is associated with a significant reduction the risk of cardiovascular events. However, the underlying mechanisms of this effect are unclear. AGIs were recently suggested to participate in stimulating glucagon-like peptide 1 (GLP-1) secretion. We therefore examined the effects of a 24-week treatment of acarbose on endogenous GLP-1, nitric oxide (NO) levels, nitric oxide synthase (NOS) activity, and carotid intima-media thickness (CIMT) in newly diagnosed patients with type 2 diabetes (T2D). METHODS: Blood was drawn from 24 subjects (14 male, 10 female, age: 50.7 ± 7.36 years, BMI: 26.64 ± 3.38 kg/m2, GHbA1c: 7.00 ± 0.74%) with drug-naïve T2D at 0 and 120 min following a standard mixed meal for the measurements of active GLP-1, NO and NOS. The CIMT was measured prior to and following 24 weeks of acarbose monotherapy (mean dose: 268 mg daily). RESULTS: Following 24 weeks of acarbose treatment, both fasting and postprandial plasma GLP-1 levels were increased. In patients with increased postprandial GLP-1 levels, serum NO levels and NOS activities were also significantly increased and were positively related to GLP-1 levels. Although the CIMT was not significantly altered following treatment with acarbose, a decreased CIMT was negatively correlated with increased GLP-1 levels. CONCLUSIONS: Twenty-four weeks of acarbose monotherapy in newly diagnosed patients with T2D is associated with significantly increased levels of both fasting and postprandial GLP-1 as well as significantly increased NO levels and NOS activity for those patients in whom postprandial GLP-1 levels were increased. Therefore, the benefits of acarbose on cardiovascular risk may be related to its stimulation of GLP-1 secretion.

[Research on the effect of statins on insulin secretion from pancreatic islet in rats and its mechanisms].

OBJECTIVE: To evaluate the inhibitory effect of statins on glucose-stimulated insulin secretion (GSIS) of pancreatic islet in rat and to explore its mechanisms. METHODS: According to the average volume, freshly isolated or 24-hour cultured pancreatic islets were randomly divided into control group (incubated with Kreb-Ringer bicarbonate buffer), the atorvastatin group (incubated with 100 µmol/L atorvastatin), the fluvastatin group (incubated with 100 µmol/L fluvastatin) and the pravastatin group (incubated with 100 µmol/L pravastatin). Stimulated by 2.8, 5.5, 11.1, 16.7 mmol/L and 25.0 mmol/L glucose respectively, the effect of 100 µmol/L statins on ATP content and GSIS was compared in the four groups. GSIS was performed by the 37°C bath incubation method and ATP content was measured by chemiluminescence method. RESULTS: Incubated with 100 µmol/L atorvastatin for 30 minutes, in the presence of 16.7 mmol/L glucose, the ATP content [(9.54 ± 1.64) pmol/islet vs (12.33 ± 1.89) pmol/islet] and GSIS (1.60 ± 0.21 vs 2.39 ± 0.30) were significantly reduced in comparison with the control group (P < 0.05). Cultured with 100 µmol/L fluvastatin for 24 hours, the ATP content [(10.24 ± 2.01) pmol/islet vs (12.31 ± 2.16) pmol/islet] and GSIS (3.12 ± 0.32 vs 4.17 ± 0.37) were all significantly decreased at the higher glucose concentration of 16.7 mmol/L (P < 0.05). CONCLUSION: Atorvastatin and fluvastatin may inhibit GSIS by decreasing ATP content in pancreatic islet and the inhibitory effect is related to the strength of its lipophilicity.