The CLOCK protein regulates insulin secretion related with L-type calcium channels in rat pancreatic beta cells.

BACKGROUND: Circadian locomotor output cycles kaput protein (CLOCK) plays a crucial role in glucose homeostasis and controlling insulin secretion. However, the mechanism of the CLOCK regulating rhythmic insulin secretion has not been fully understood. METHODS: Rhythmic expression of the CLOCK in rat pancreatic beta cell was detected. INS-1 cells were transfected with siRNAs to knockdown the CLOCK before the cells were incubated with different concentrations of glucose. Insulin secretion was analyzed by ELISA method. Expression of the L-type calcium channel protein (Cav1.2, Cacna1c) was determined both in the CLOCK-knockdown cells and the control cells. Calcium influx was probed by fluorescent. Chromatin immunoprecipitation (ChIP) test and dual-luciferase reporter gene experiments were applied to verify the relationship between the CLOCK and Cav1.2. RESULTS: The CLOCK is abundantly expressed in rat pancreatic beta cells. Transcription level of the CLOCK showed rhythmicity in the beta cells. Compared to the control group, insulin release was significantly impaired with 25 mM glucose incubation in the CLOCK-knockdown group, but not showed with 2.5 mM glucose incubation. The expression of Cav1.2 and the influx of calcium were significantly decreased in the CLOCK-knockdown group with 25 mM glucose incubation. ChIP test indicted that the CLOCK bound to -444∼-454 region of the Cacna1c promoter of the INS-1 cells, but the binding was significantly reduced following the CLOCK-knockdown. Luciferase experiment was in accordance with the finding of ChIP. CONCLUSIONS: The CLOCK mediating Cav1.2 expression may point out a potential pathway of circadian rhythm affecting insulin secretion.

Impact of inflammatory markers on the relationship between sleep quality and diabetic kidney disease.

PURPOSE: Both poor sleep and diabetic kidney disease are closely associated with inflammation. However, the correlation between poor sleep and diabetic kidney disease has not been well clarified. Thus, the aim of this study was to determine the mediating role that inflammatory markers play in the pathogenic effect of poor sleep on the severity of diabetic kidney disease (DKD). METHODS: A cross-sectional survey was conducted on 336 patients with type 2 diabetes (T2D). DKD was diagnosed according to the guidelines of the National Kidney Foundation-Kidney Disease Outcome Quality Initiative (NKF-K/DOQI). The Pittsburg Sleep Quality Index (PSQI) score was applied to assess patients for the quality of their sleep. Patients with a PSQI score of more than 5 were assigned to the poor sleep group, and the rest of the patients were assigned to the good sleep group. Circulating levels of six inflammatory biomarkers related to poor sleep and DKD were measured. RESULTS: The prevalence of DKD was higher in patients with poor sleep quality than in those with good sleep quality (42% vs. 25%, P = 0.002). After adjustment, poor sleep quality (PSQI score OR 1.075 [95%CI 1.018-1.135], P = 0.009) remained independently associated with DKD. PSQI score was found to be positively related to fibroblast growth factor (FGF23), interleukin 6 (IL-6), P-selectin, and intercellular adhesion molecule-1 (ICAM-1) (P < 0.01), rather than fibrinogen and C-reactive protein (CRP) in linear regression models. As revealed by multiple mediation analysis, FGF23 and IL-6 mediated 26% and 23% of the relationship between PSQI score and urinary microalbumin (UMA), respectively. Similarly, the FGF23 and ICAM-1, instead of IL-6 and P-selectin, mediated 32% and 24% of the association between PSQI and estimated glomerular filtration rate (eGFR), respectively. CONCLUSIONS: Poor sleep quality is independently associated with DKD. These results suggest that inflammatory markers contribute to a pathogenic connection between poor sleep and DKD.

Type 2 diabetes, insulin treatment and prognosis of breast cancer.

BACKGROUND: The aim of our study was to investigate whether pre-existing type 2 diabetes and insulin therapy have an impact on the prognosis of breast cancer patients. METHODS: We performed a retrospective analysis of 462 type 2 diabetic breast cancer patients and 1644 non-diabetic breast cancer patients treated in our institute from January 2005 to August 2010. Patients were divided by diabetes status and insulin use. The clinicopathological characteristics and clinical outcomes of patients within 5 years following breast cancer diagnosed were analysed. RESULTS: Diabetic patients tended to have higher body mass index and higher histological grade tumours. Five-year disease-free survival and overall survival were reduced in diabetic patients (P < 0.001), and diabetes was an independent predictor for an increased risk of breast cancer relapse and death within 5 years (P < 0.001). Insulin treatment was associated with reduced 5-year disease-free survival and overall survival (P < 0.05); the risk of 5-year relapse and breast cancer mortality in the insulin group increased compared to that of non-insulin group after adjusting for age, tumour size, histological grade, oestrogen receptor, progesterone receptor, chemotherapy and hormone therapy (P < 0.05). After adjusting for age and other factors, the risk of breast cancer relapse was also increased in the insulin subgroup, while the risk of breast cancer mortality did not increase statistically. CONCLUSIONS: Type 2 diabetes and insulin treatment might be independently associated with poorer prognosis of breast cancer. However, caution is needed when interpreting our results, and further investigations are needed. Copyright © 2016 John Wiley & Sons, Ltd.

[The mechanism of inhibition of the increase in intracellular calcium concentration by the islet amyloid polypeptide in high glucose-stimulated INS-1 cells].

OBJECTIVE: To explore the potential mechanism of the inhibition of increased intracellular free calcium concentration ([Ca²âº]i) by short-term exposure to the islet amyloid polypeptide (IAPP) in high glucose-stimulated pancreatic ß cells. METHODS: The pancreatic ß cells were loaded with calcium sensitive fluorescent indicator Fluo-4/AM. The fluorescence intensity, which represented [Ca²âº]i, was measured in time by laser scanning confocal microscope before and after stimulated by glucose, KCl, caffeine and carbachol. RESULT: The fluorescence intensity F/F0 in INS-1 cells, increased to about 2 folds after glucose stimulation. After the exposure to the IAPP with different concentration, the fluorescence intensity F/F0 was decreased slightly in the pretreated cells by 16.7 mmol/L glucose with 0.5 µmol/L IAPP. However, after the pretreatment of IAPP with the concentration of 1.0, 5.0, 10.0 µmol/L, the fluorescence intensity F/F0 showed a dose-dependent decrease with statistical difference. The fluorescence intensity F/F0 in the cells increased rapidly in a peak pattern after the stimulation of 30 mmol/L KCl. But with the pretreatment of 10.0 µmol/L IAPP, the fluorescence intensity F/F0 decreased with statistical difference. With 20 mmol/L caffeine and 100 µmol/L carbachol which stimulated Ca²âº release respectively from internal ryanodine receptor (RYR) and inositol triphosphate (IP3) Ca²âº storage, the fluorescence intensity F/F0 curve presented a peak pattern. After 10 µmol/L IAPP pretreatment, the fluorescence intensity F/F0 showed no statistical difference from the control group. CONCLUSIONS: The short-term effect of IAPP on pancreatic ß cells has no influence on the caffeine and carbachol stimulated Ca²âº release from endoplasmic reticulum RYR and IP3 Ca²âº storage. The inhibition of calcium increase in INS-1 cells by short-term exposure to IAPP may mainly via inhibiting the voltage-gated L-calcium channels with intact release capacity of Ca²âº storage.

[Risk factors for infections of methicillin-resistant Staphylococci in diabetic foot patients].

OBJECTIVE: To examine the distribution patterns of pathogens isolated from the patients with diabetic foot ulcers and explore the risk factors for infections of methicillin-resistant S. aureus (MRSA) or methicillin-resistant S. epidermidis (MRSE). METHODS: A total of 388 diabetic-foot patients hospitalized at Tianjin Metabolic Diseases Hospital between January 2008 and June 2010 were recruited. The distribution profiles of pathogens isolated from diabetic foot ulcers were summarized. The patients with S. aureus infections were divided into MRSA and MSSA groups while those with S. epidermidis infections into MRSE and MSSE groups. The clinical features of these patients were compared between all groups. Logistic regression was employed to identify the risk factors for the MRSA/MRSE infections. RESULTS: A total of 362 pathogens were isolated from them. And the Gram-positive bacteria were the most predominant (57.2%, 207/362), followed by Gram-negative bacilli (39.2%, 142/362) and true fungi (3.6%, 13/362). The three most frequently isolated pathogens were S. aureus (27.1%), S. epidermidis (18.8%) and Pseudomonas aeruginosa (15.5%). Statistically significant differences existed in antibiotic usage in 6 months prior to hospitalization, course of ulcer, ulcer size, deep ulcer, osteomyelitis, hypertension, anemia, hypoproteinemia and erythrocyte sedimentation rate between the patients infected with MRSA and MSSA (P < 0.05). The MRSE infection was correlated with recurrent ulcer, osteomyelitis, hypoproteinemia, HbA1c and lower total serum protein (P < 0.05). Multiple Logistic regression analysis revealed that antibiotic usage in 6 months prior to hospitalization, long course of ulcer, osteomyelitis, hypertension and hypoproteinemia were risk factors for the MRSA infection. And HbA1c was a risk factor for the MRSE infection. CONCLUSION: In the present study, the Gram-positive cocci are the main pathogens isolated from diabetic foot ulcers. And S. aureus and S. epidermidis are the most frequently isolated pathogens. Antibiotic usage in 6 months prior to hospitalization, long course of ulcer, osteomyelitis, hypertension and hypoproteinemia are risk factors for the MRSA infection. And HbA1c is a risk factor for the MRSE infection.

Nanotechnology promotes the full-thickness diabetic wound healing effect of recombinant human epidermal growth factor in diabetic rats.

We utilized a modified double-emulsion method with poly(lactic-co-glycolic acid) as the carrier to prepare recombinant human epidermal growth factor (rhEGF) nanoparticles. The morphology of the nanoparticles was detected by a transmission electron microscope. The particle size distribution was measured by a laser analyzer with a zeta potential meter. Enzyme-linked immunosorbent assays were performed to determine the rhEGF encapsulation efficiency and release model, and the proliferation of the mouse fibroblasts was analyzed by the MTT method. Diabetic rats with full-thickness wounds were divided into four groups according to different treatments: rhEGF nanoparticles, rhEGF stock solution, empty nanoparticles, and phosphate-buffered saline. Photographs were taken after the treatments to calculate the wound healing rates, and the granulation tissue of the wounds was sampled for pathologic slides. Proliferating cell nuclear antigen was assayed by immunohistochemistry. Our results showed that the rhEGF nanoparticles were around 193.5 nm (diameter), and the particle size distribution was uniform and dispersible. The encapsulation efficiency was 85.6% and rhEGF release lasted 24 hours. Compared with other groups, the rhEGF nanoparticles promoted the highest level of fibroblast proliferation, and this group showed the fastest healing rate. The number of proliferating cell nuclear antigen positive cells in the rhEGF nanoparticles group was higher than the other groups. We concluded that controlled release of rhEGF encapsulated in the nanoparticles enhanced rhEGF effects to stimulate cell proliferation and shorten the wound healing time.

[Effects of root extract of host plants on seed germination and haustorium formation of Cistanche deserticola]. / å¯„ä¸»æ¤ç‰©æ ¹æµ¸ææ¶²å¯¹è‚‰è‹è“‰ç§å­èŒå‘åŠå¸å™¨å½¢æˆçš„å½±å“.

We examined the effects of root extracts of Haloxylon ammodendron and Beta vulgaris in Chenopodiaceae extracted by water and ethanol on seed germination and haustorium formation of Cistanche deserticola by filter paper culture dish method. The results showed that only adding root extract had no effect on seed germination and haustorium formation of C. deserticola. The germination rate of C. deserticola seeds treated by adding 10 mg·kg-1 gibberellin to the root extracted by ethanol was not significantly different from that of the control (GA3), whereas those treated by adding gibberellin to the ethanol extract of two kinds of host root was increased by more than 10 times. The germination rate of C. deserticola seeds in the treatment with adding 1 mg·kg-1 fluridone (FL) to root extract was not significantly different from that in the control with only fluridone, while those in the treatment with B. vulgaris root water extraction was the highest (39.4%). Compared to the treatment of adding gibberellin to the root extract, the germination rate of C. deserticola seeds was only increased. When FL was added to the host root extract, the haustorium was formed on the germination tube, with the formation rate of the ethanol extraction group being the highest (16.2%). Seed germination rate of C. deserticola increased to 52.3% when GA3 and FL were added to the ethanol extract of H. ammodendron, but the formation rate of haustorium was not different from that of FL treatment. Only 6.7% of the seed formation haustorium in the control was significantly lower than that in FL treatment. There were differences in the position and shape of the haustorium of C. deserticola seeds under different treatments. The haustorium produced by adding the extract of the host root mostly appeared at the top of the bud tube, and many papillae raised into claws. The haustorium of FL treatment without adding the extract of the host root mostly appeared at the bottom or the top of the bud tube splitting. The results indicated that ethanol extraction and water extraction could extract the substances that could promote the formation of C. deserticola seeds haustorium from the host root, but did not affect seed germination. GA3 and FL could significantly improve the germination rate of C. deserticola seeds, but the formation of the haustorium was affected by some substances in the host root extract.

A Mixed-ligand Zn(II)-based Coordination Polymer for Selectively Detect 2,4,6-Trinitrophenol (TNP) and Treatment Effect on Periodontal Diseases via Inhibition Effect on P. gingivalis Growth.

A new difunctional Zn(II) coordination polymer (CP) with the chemical formula of [Zn(TBTA) (L)1.5]n (1) has been synthesized hydrothermally from tetrabromoterephthalic acid (H2TBTA) and 4,4'-bis(imidazole-1-yl)-biphenyl (L) ligands. Furthermore, due to its strong intense emission and open N donor sites, complex 1 could be used as a light-emitting sensor to determine 2,4,6-trinitrophenol (TNP) which has high selectivity and sensitivity. Furthermore, the anti-bacterial effect of the compound against P. gingivalis in vitro was evaluated by measuring the P. gingivalis growth curves after compound treatment. And the RT-PCR assay was performed to detect the relative expression of ragA and ragB, which are important for the P. gingivalis growth. The potential anti-infectious mechanism was further studied by using molecular docking technique.

A Mobile-Based Intervention for Glycemic Control in Patients With Type 2 Diabetes: Retrospective, Propensity Score-Matched Cohort Study.

BACKGROUND: Mobile-based interventions appear to be promising in ameliorating huge burdens experienced by patients with type 2 diabetes. However, it is unclear how effective mobile-based interventions are in glycemic management of patients with type 2 diabetes based on real-world evidence. OBJECTIVE: This study aimed to evaluate the effectiveness of a mobile-based intervention on glycemic control in patients with type 2 diabetes based on real-world population data. METHODS: This retrospective, propensity score-matched cohort study analyzed longitudinal data from a clinical electronic health database. The study population included 37,913 patients with type 2 diabetes at cohort entry between October 1, 2016, and July 31, 2018. A total of 2400 patients were matched 1:1, using propensity score matching, into the usual care and mobile health (mHealth) groups. The primary outcomes of glycemic control included control rates of glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and postprandial 2-hour blood glucose (P2BG). Mean values and variation trends of difference with 95% CI were the secondary outcomes. The general linear model was used to calculate repeated-measures analyses of variance to examine the differences between the two groups. Subgroup and sensitivity analyses were performed. RESULTS: Of the 2400 patients included in the analysis, 1440 (60.00%) were male and the mean age was 52.24 years (SD 11.56). At baseline, the control rates of HbA1c, FBG, and P2BG in the mHealth and usual care groups were 45.75% versus 47.00% (P=.57), 38.03% versus 32.76% (P=.07), and 47.32% versus 47.89% (P=.83), respectively. At the 3-, 6-, 9-, and 12-month follow-ups, the mHealth group reported higher control rates of HbA1c than did the usual care group: 69.97% versus 46.06% (P<.001), 71.89% versus 61.24% (P=.004), 75.38% versus 53.44% (P<.001), and 72.31% versus 46.70% (P<.001), respectively. At the four follow-up sessions, the control rates of FBG in the mHealth and usual care groups were statistically different: 59.24% versus 34.21% (P<.001), 56.61% versus 35.14% (P<.001), 59.54% versus 34.99% (P<.001), and 59.77% versus 32.83% (P<.001), respectively. At the four follow-up sessions, the control rates of P2BG in the mHealth group were statistically higher than in the usual care group: 79.72% versus 48.75% (P<.001), 80.20% versus 57.45% (P<.001), 81.97% versus 54.07% (P<.001), and 76.19% versus 54.21% (P=.001), respectively. At the four follow-up sessions, the percentages of HbA1c reduction in the mHealth group were 8.66% (95% CI 6.69-10.63), 10.60% (95% CI 8.66-12.54), 10.64% (95% CI 8.70-12.58), and 8.11% (95% CI 6.08-10.14), respectively. At the four follow-up sessions, the percentages of P2BG reduction in the mHealth group were 8.44% (95% CI 7.41-10.73), 17.77% (95% CI 14.98-20.23), 16.23% (95% CI 13.05-19.35), and 16.91% (95% CI 13.17-19.84), respectively. Starting from the sixth month, the mean HbA1c and P2BG values in the two groups increased slightly. CONCLUSIONS: This mobile-based intervention delivered by a multidisciplinary team can better improve glycemic control rates of patients with type 2 diabetes than usual care. These effects were best sustained within the first 6 months. Starting from the sixth month, intensive management needs to be conducted to maintain long-term effectiveness of the mobile-based intervention.

Correlation between inflammatory markers and impaired circadian clock gene expression in type 2 diabetes mellitus.

AIM: Circadian rhythm controls a wide variety of physiological processes in the body. Disruption of the circadian clock in metabolic tissues may increase the risk of diabetes, obesity, and metabolic syndrome. The following study investigated whether the expression of clock genes of peripheral blood cells is impaired in type 2 diabetes (DT2) and whether inflammatory markers are associated with circadian clock gene expression in DT2 patients. MATERIALS AND METHODS: Blood samples were obtained from 36 DT2 patients and 14 non-diabetic volunteers. Transcript levels of circadian clock genes were analyzed using real-time quantitative PCR; plasma inflammatory markers were measured by ELISA or clinical laboratory test. RESULTS: The CLOCK, BMAL1, PER1, CRY1 and CRY2 mRNA levels were decreased in the diabetic patients. In addition, HbA1c levels were negatively correlated with BMAL1, PER1 and CRY1 mRNA levels. The levels of IL-6, TNF-α and CRP were higher in diabetic subjects compared to control subjects. Impaired expression of circadian clock gene was interrelated with the elevated levels of plasma IL-6 and TNF. Moreover, a multiple linear regression showed that plasma IL-6 level was correlated with impaired expression of circadian clock gene. CONCLUSIONS: Circadian clock genes are reduced in peripheral leucocytes of DT2 patients. Furthermore, impaired expression of circadian clock gene are interrelated with the elevated levels of plasma inflammatory markers.

Dynamics of Soil Respiration in Alpine Wetland Meadows Exposed to Different Levels of Degradation in the Qinghai-Tibet Plateau, China.

The effects of degradation of alpine wetland meadow on soil respiration (Rs) and the sensitivity of Rs to temperature (Q10) were measured in the Napa Lake region of Shangri-La on the southeastern edge of the Qinghai-Tibet Plateau. Rs was measured for 24 h during each of three different stages of the growing season on four different degraded levels. The results showed: (1) peak Rs occurred at around 5:00 p.m., regardless of the degree of degradation and growing season stage, with the maximum Rs reaching 10.05 µmol·m-2·s-1 in non-degraded meadows rather than other meadows; (2) the daily mean Rs value was 7.14-7.86 µmol·m-2·s-1 during the mid growing season in non-degraded meadows, and declined by 48.4-62.6% when degradation increased to the severely degraded level; (3) Q10 ranged from 7.1-11.3 in non-degraded meadows during the mid growing season, 5.5-8.0 and 6.2-8.2 during the early and late growing seasons, respectively, and show a decline of about 50% from the non-degraded meadows to severely degraded meadows; (4) Rs was correlated significantly with soil temperature at a depth of 0-5 cm (p < 0.05) on the diurnal scale, but not at the seasonal scale; (5) significant correlations were found between Rs and soil organic carbon (SOC), between biomass and SOC, and between Q10 and Rs (p < 0.05), which indicates that biomass and SOC potentially impact Q10. The results suggest that vegetation degradation impact both Rs and Q10 significantly. Also, we speculated that Q10 of alpine wetland meadow is probable greater at the boundary region than inner region of the Qinghai-Tibet Plateau, and shoule be a more sensitive indicator in the studying of climate change in this zone.

CaV2.3 calcium channels control second-phase insulin release.

Concerted activation of different voltage-gated Ca( (2+) ) channel isoforms may determine the kinetics of insulin release from pancreatic islets. Here we have elucidated the role of R-type Ca(V)2.3 channels in that process. A 20% reduction in glucose-evoked insulin secretion was observed in Ca(V)2.3-knockout (Ca(V)2.3(-/-)) islets, close to the 17% inhibition by the R-type blocker SNX482 but much less than the 77% inhibition produced by the L-type Ca(2+) channel antagonist isradipine. Dynamic insulin-release measurements revealed that genetic or pharmacological Ca(V)2.3 ablation strongly suppressed second-phase secretion, whereas first-phase secretion was unaffected, a result also observed in vivo. Suppression of the second phase coincided with an 18% reduction in oscillatory Ca(2+) signaling and a 25% reduction in granule recruitment after completion of the initial exocytotic burst in single Ca(V)2.3(-/-) beta cells. Ca(V)2.3 ablation also impaired glucose-mediated suppression of glucagon secretion in isolated islets (27% versus 58% in WT), an effect associated with coexpression of insulin and glucagon in a fraction of the islet cells in the Ca(V)2.3(-/-) mouse. We propose a specific role for Ca(V)2.3 Ca(2+) channels in second-phase insulin release, that of mediating the Ca(2+) entry needed for replenishment of the releasable pool of granules as well as islet cell differentiation.

Effects and mechanism of glucagon-like peptide-1 on injury of rats cardiomyocytes induced by hypoxia-reoxygenation.

BACKGROUND: Although the insulinotropic role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes mellitus has been substantiated, its role in cardioprotection remains largely unknown. This study aimed to determine the effects of GLP-1 on injury of rats cardiac myocytes induced by hypoxia-reoxygenation (H/R) and the possible mechanisms. METHODS: The cultured neonatal rats cardiac myocytes were randomly divided into seven groups: the normal control group, the H/R group, the GLP-1 + H/R group, the GLP-1 + H/R + UO126 (the p42/44 mitogen-activated protein kinase (MAPK) inhibitor) group, the GLP-1 + H/R + LY294002 (phosphatidylinositol 3-kinase (PI3K) inhibitor) group, the H/R + UO126 group, and the H/R + LY294002 group. The lactate dehydrogenase (LDH) activity, apoptosis rate of cardiac myocytes, and caspase-3 activity were detected after the injury of H/R. RESULTS: Compared with the normal control group, the activity of LDH, cardiac myocyte apoptosis rate, and caspase-3 activity all increased significantly in the H/R group (P < 0.01). Compared with the H/R group, these three indices all decreased in the H/R + GLP-1 group (P < 0.01). However, the changes of LDH activity, apoptosis rate, and caspase-3 activity were inhibited by LY294002 and UO126 respectively. CONCLUSIONS: GLP-1 can directly act on cardiac myocytes and protect them from H/R injury mainly by inhibiting their apoptosis. Its mechanism may be through the PI3K-Akt pathway and the MAPK signaling pathway.

Effect of Diabetes Sleep Education for T2DM Who Sleep After Midnight: A Pilot Study from China.

BACKGROUND: Our prior study showed that patients with sleep disorders had poor blood pressure (BP), glycemic control, and more severe complications. Therefore, sleep is very important for diabetic control. Our work was to investigate whether individualized diabetes sleep education significantly improve sleep quality and glycemic control in type 2 diabetic patients who sleep after midnight and potential mechanism by a randomized parallel interventional study. METHODS: T2D patients were randomly recruited to an intervention or control group. Patients received structured special diabetes sleep education program with 3-month follow-up. Pittsburg Sleep Quality Index (PSQI) was scored for each participant. Demographic data, HbA1c, biochemical, and some hormones were also examined. SPSS 13.0 was used for statistical analysis. RESULTS: One hundred patients were approached, and 45 were enrolled into our trial. Eventually, 31 patients completed the study. Patients in the intervention group greatly improved their sleep hygiene. After intervention, PSQI scores were lowered significantly (-1.48 ± 0.88 vs. -0.51 ± 0.71, P < 0.001), as well as significant reduction of HbA1c (-1.5 ± 0.55 vs. -1.11 ± 0.47, P < 0.05). Fasting plasma glucose was also lowered significantly. Homeostasis model assessment of insulin resistance was reduced significantly (-1.29 ± 0.97 vs. 1.04 ± 0.91, P < 0.01). Serum concentrations for interleukin (IL)-6, cortisol, and ghrelin were decreased significantly. Ghrelin (coefficients -0.65, P < 0.001), cortisol (coefficients -0.38, P < 0.05), and IL-6 (coefficients 0.452, P < 0.05) were correlated with HbA1c improvement. The change of ghrelin was negatively associated with the improvement of HbA1c. CONCLUSION: Diabetes sleep education could improve sleep quality, better blood glucose and BP, and decrease insulin resistance through healthier sleep hygiene. Lower serum concentration of ghrelin might be partly involved in the reduction of HbA1c.

Glucagon-like peptide-1 potentiates glucose-stimulated insulin secretion via the transient receptor potential melastatin 2 channel.

The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+ permeable channel activated by cAMP, is expressed on pancreatic ß-cells and is responsible for the regulation of insulin secretion. It is known that glucose-stimulated insulin secretion (GSIS) can be potentiated by glucagon like peptide-1 (GLP-1), and that the changes in the extracellular glucose concentration alter the levels of intracellular adenosine ATP and cAMP. The present study hypothesized that TRPM2 mediates the modulatory effect of GLP-1 on insulin secretion. The results demonstrated that silencing of TRPM2 eliminated GLP-1-enhanced insulin secretion, indicating the involvement of TRPM2 in this process. In addition, the results of current recordings of TRPM2 and measurement of the resulting insulin secretion in ß-cells in the presence of GLP-1 and various concentrations of glucose suggest that GLP-1 regulates GSIS via the TRPM2 channel. Furthermore, inhibiting the activity or expression of TRPM2 attenuated GLP-1-induced GSIS. By using specific activators or inhibitors, the present study demonstrated that the two primary downstream effectors of the GLP-1 receptor, exchange protein directly activated by cAMP and protein kinase A, differentially influence GSIS and GLP-1-potentiated GSIS. In conclusion, the present study revealed the role of TRPM2 in GLP-1-regulated insulin secretion. The results of the present study provide a novel avenue for the prevention and treatment of diabetes and its complications.

Association of diabetic vascular complications with poor sleep complaints.

BACKGROUND: Literatures reported that poor sleep complaints were associated with a great deal of health outcomes. However, there are few studies on the association of poor sleep complaints with diabetic vascular complications. METHODS: Aiming on the association, a cross-sectional survey was conducted among 1220 diabetic patients in this study. Poor sleep complaints were composed of difficulty falling asleep, early final awakening, short sleep and long sleep. The diabetic vascular complications involved in the study were diagnosed according to the Standards of Medical Care in Diabetes (ADA 2016). RESULTS: Our findings indicated that short sleep remained independently associated with diabetic kidney disease (DKD) (OR > 1, P < 0.05) after the adjustments; long sleep independently associated with diabetic retinopathy (DR) (OR > 1, P < 0.05); early final awakening and short sleep independently associated with cardiovascular disease (OR > 1, P < 0.05); short sleep independently associated with peripheral arterial disease (OR > 1, P < 0.05); there was no association between poor sleep complaints and neuropathy (P > 0.05). CONCLUSIONS: The study suggests that the poor sleep complaints were distinguishably associated with diabetic vascular complications. Clinicians should take poor sleep complaints into account in diabetes treatment.

Comparative efficacy and safety of urate-lowering therapy for the treatment of hyperuricemia: a systematic review and network meta-analysis.

The prevalence of hyperuricemia and gout has been increasing, but the comparative effectiveness and safety of different treatments remain uncertain. We aimed to compare the effectiveness and safety of different treatments for hyperuricemia using network meta-analysis methodology. We systematically reviewed fifteen randomized controlled trials (involving 7,246 patients through January 2016) that compared the effects of different urate-lowering drugs (allopurinol, benzbromarone, febuxostat, pegloticase and probenecid) on hyperuricemia. Drug efficacy and safety, as outcomes, were measured by whether the target level of serum urate acid was achieved and whether any adverse events occurred, respectively. We derived pooled effect sizes expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The efficacy and safety of the drugs were ranked by cumulative ranking probabilities. Our findings show that febuxostat, benzbromarone, probenecid, pegloticase, and allopurinol were all highly effective at reducing the risk of hyperuricemia compared to placebo. Febuxostat had the best efficacy and safety compared to the other drugs. Furthermore, febuxostat 120 mg QD was more effective at achieving urate-lowering targets (OR: 0.17, 95% CI: 0.12-0.24) and safer (OR: 0.72, 95% CI: 0.56-0.91) than allopurinol.

Adiponectin-derived active peptide ADP355 exerts anti-inflammatory and anti-fibrotic activities in thioacetamide-induced liver injury.

Adiponectin is an adipocyte-derived circulating protein with beneficial effects on injured livers. Adiponectin-deficient (adipo(-/-)) mice develop enhanced liver fibrosis, suggesting that adiponectin could be a therapeutic target for liver injury. In the present study, we investigated the protective role of ADP355, an adiponectin-based active short peptide, in thioacetamide (TAA)-induced acute injury and chronic liver fibrosis in mice. ADP355 remarkably reduced TAA-induced necroinflammation and liver fibrosis. ADP355 treatment increased liver glycogen, decreased serum alanine transaminase and alkaline phosphatase activity, and promoted body weight gain, hyper-proliferation and hypo-apoptosis. In addition, ADP355 administration suppressed the TAA-induced activation of hepatic stellate cells and macrophages in the liver. These were associated with the inactivation of TGF-ß1/SMAD2 signaling and the promotion of AMPK and STAT3 signaling. Sensitivity of adipo(-/-) mice to chronic liver injury was decreased with ADP355. In conclusion, ADP355 could mimic adiponectin's action and may be suitable for the preclinical or clinical therapy of chronic liver injury.

Plumbagin protects liver against fulminant hepatic failure and chronic liver fibrosis via inhibiting inflammation and collagen production.

Plumbagin is a quinonoid constituent extracted from Plumbago genus, and it exhibits diverse pharmacological effects. This study thoroughly investigated the effects of plumbagin on thioacetamide-induced acute and chronic liver injury. Results shown that plumbagin increased survival rate, reduced liver congestion and inflammation, and decreased macrophages and neutrophils in the fulminant hepatic failure model, and remarkably diminished liver fibrosis and inflammation in the chronic liver injury model. Furthermore, plumbagin significantly suppress the HSCs/myofibroblasts activation by reduced expression of markers α-SMA and COL-1/3, and reduced macrophage in liver. In the in vitro study, plumbagin induced apoptosis and suppressed the proliferation of LX-2 cells (human HSCs). Plumbagin treatment increased AMPK phosphorylation and attenuated NF-κB, STAT3, and Akt/mTOR signals in LX-2 cells, while SMAD2 phosphorylation was not changed. Noticeably, plumbagin promoted AMPK binding to p300 which is a cofactor of SMAD complex, this may further competitively decreases the p300/SMAD complex initiated transcription of COL-1/3 and α-SMA. Additionally, plumbagin hampered inflammation related NF-κB signal in RAW 264.7 cells. In conclusion, these findings indicate that plumbagin may be a powerful drug candidate to protect the liver from acute and chronic damage by inhibiting inflammation and collagen production.