Predicting the efficacy of donepezil intervention in Alzheimer's disease patients using regional homogeneity in the inferior orbitofrontal cortex.

BACKGROUND: Although donepezil is a commonly used drug for treating Alzheimer's disease (AD), the mechanisms by which it affects patients' functional brain activity, and thus modulates clinical symptoms, remain unclear. METHODS: In the present study, we used resting-state functional magnetic resonance imaging (MRI) and regional homogeneity (ReHo) to investigate the effects of donepezil on local brain activity in AD patients. Resting-state functional MRI data were collected from 32 subjects: 16 healthy controls and 16 AD patients. All 16 AD patients underwent 6 months of donepezil treatment and received two MRI scans (pre- and post-intervention). Analysis of covariance and post hoc analyses were used to compare ReHo differences among the healthy controls, pre-intervention AD patients, and post-intervention AD patients. Pearson correlation analysis was used to examine relationships between ReHo values in differential brain regions and clinical symptoms. RESULTS: Compared with healthy controls, post-intervention AD patients had reduced ReHo in the orbital part of the inferior frontal gyrus, and pre-intervention AD patients had reduced ReHo in the orbital part of the right inferior frontal gyrus. Pattern recognition models revealed that pre-intervention ReHo values in abnormal brain regions of AD patients were 76% accurate for predicting the efficacy of donepezil on cognitive function and 65% accurate for predicting its efficacy on depressive symptoms. CONCLUSIONS: These findings deepen our understanding of the brain mechanisms underlying the clinical efficacy of donepezil in AD patients, and provide a novel way to predict its clinical efficacy in such patients.

Clinical values of serum neuropeptide changes in patients with chronic urticaria complicated with allergic rhinitis.

AIM: Neurogenic inflammation has been recognized as an important contributing factor in the pathogenesis of allergic rhinitis. The aim of this study was to investigate the clinical values of substance P, vasoactive intestinal peptide (VIP), and neuropeptide Y as biomarkers of disease severity and treatment outcomes of chronic urticaria complicated with allergic rhinitis. METHODS: Our prospective study included 150 patients with chronic urticaria complicated with allergic rhinitis and 80 healthy control patients. Before treatment, the serum samples of all study subjects were collected and analyzed using enzyme-linked immunosorbent analysis. The intervention group received imipramine of 10 mg/day orally for 2 weeks, and the Symptom Score Reduction Index (SSRI) was used to analyze clinical outcomes, which were categorized as effectual and ineffectual. RESULTS: Our data suggested that substance P, VIP, and neuropeptide Y were significantly correlated to each other. Lower levels of substance P, VIP, and neuropeptide Y were associated with better treatment outcomes. A good detection sensitivity (69.49%) and specificity (80.22%) could be achieved using a combination of these markers (area under curve = 0.85). CONCLUSIONS: Our data indicates that substance P, VIP, and neuropeptide Y levels before treatment correlate strongly with the treatment outcomes of the patients, which could potentially serve as a decision support tool in clinical management of chronic urticaria complicated with allergic rhinitis.

Structural characterization and anti-osteoporosis effect of an arabinomannan from Anemarrhena asphodeloides Bge.

To discover the polysaccharide with anti-diabetic osteoporosis (DOP) activity and clarify its structure, an arabinomannan (PAAP-1B) with a molecular weight of 14.0 kDa was isolated from Anemarrhena asphodeloides Bge. using column chromatography. It consists of arabinose, mannose, and galactose in a molar ratio of 6:3:1. PAAP-1B has a backbone composed of 1,5-α-Araf, 1,4-ß-Manp, and 1,6-ß-Galp residues that are branched at C3 of α-Araf and ß-Galp residues. The side chains are T-α-Araf, T-α-Manp, T-ß-Galp, and 1,6-ß-Galp. PAAP-1B attenuated DOP and reduced ferroptosis in the femurs and tibias of alloxan-induced mice. It also suppressed ferroptosis in advanced glycation end product-induced osteoblasts by decreasing 4-hydroxynonenal, malondialdehyde, mitochondrial reactive oxidative species levels, and lipid peroxidation, while reversing the downregulation of solute carrier family 7 membrane 11 and glutathione expression.

One-step microwave synthesis of red-emissive carbon dots for cell imaging in extreme acidity and light emitting diodes.

Red emissive carbon dots (R-CDs) have received great attention in biological fields due to their deep tissue penetrability, great bioimaging capability, low interference from auto-fluorescence, and potential for optoelectronic applications. Herein, excitation-independent, highly acid-sensitive R-CDs were successfully obtained via one-step microwave treatment of o-phenylenediamine (o-PD) and phosphoric acid and carefully purified by column chromatography. The relationship between the fluorescence emission and surface groups of the R-CDs was studied in detail using XPS, NMR, and fluorescence spectroscopy, and the different mechanisms of action of the R-CDs and acid in H2O and ethanol were determined. The excellent anti-interference ability and biocompatibility of the R-CDs were confirmed, and the probes were successfully used for imaging A549 and Escherichia coli (E. coli) cells in extreme acidity. Finally, based on their relatively high quantum yield and long wavelength emission, the application potential of the R-CDs in the fabrication of red light-emitting diodes (LEDs) was investigated.

Effects of Danggui-Shaoyao-San on depression- and anxiety-like behaviors of rats induced by experimental tooth movement.

PURPOSE: To investigate the effects of Danggui-Shaoyao-San (DSS) on depression- and anxiety-like behavior induced by experimental tooth movement (ETM) in rats. MATERIALS AND METHODS: Thirty-six rats were randomly divided into a sham group (n = 12; rats underwent all operation procedures, except placement of orthodontic forces, and received saline treatment), ETM group (n = 12; rats received saline treatment and ETM), and DETM group (n = 12; rats received DSS [dose: 150 mg/kg twice daily from preoperative day 5 to postoperative day 7] treatment and ETM). The vacuous chewing movement (VCM) test, open-field test, and elevated plus maze test were performed to assess the depression- and anxiety-like behaviors of the rats. RESULTS: DSS pretreatment significantly decreased the ETM-induced VCM time (P < 0.05, DETM vs. ETM), increased the ETM-induced time to the central area of experimental device during the 5 min open-field test (P < 0.05, DETM vs. ETM), and increased the ratio of time spent in the open arms of the 5 min elevated plus maze test induced by ETM (P < 0.01, DETM vs. ETM). CONCLUSIONS: DSS pretreatment can restore the impaired abilities of rats caused by ETM-induced depression- and anxiety-like behavior.

A pilot study of mandibular expansion in combination with a fixed-appliance for increasing the effective space of the mandibular arch: Finite element analysis and three-dimensional cone-beam computed tomography.

ABSTRACT: Techniques for enhancing the effective space of the mandibular arch are urgently needed. Therefore, this study aimed to perform mandibular expansion in combination with a fixed-appliance technique, with preliminary monitoring by finite element analysis and 3-dimensional cone-beam computed tomography (CBCT).Finite element models were structured according to CBCT images of a 14-year-old girl. The von Mises stress of the alveolar bone and tooth displacement were assessed in different models. The technique was also applied in an 11-year-old boy. CBCT was performed at post-expansion, post-retention, post-treatment and 2 years after treatment. Tooth movement and alveolar bone stress were assessed by the CAD software.Finite element analysis suggested that the teeth tended to stand upright in the buccal side in the expander model compared with the expander-remove model. However, minimum tooth change was observed in the normal model, indicating highest stability. The von Mises stress of the alveolar bone was decreased in the normal model compared with the expander model, suggesting that buccal-inclined teeth could more easily lead to alveolar bone stress than normal ones. Based on CBCT data and the 3D mandibular dentition model fitting, mandibular teeth tended to be upright in the buccal side after retention compared with the post-expansion condition, which somewhat differed from finite element analysis results. Furthermore, dehiscence and fenestration were not observed.This expansion technique is expected to increase the effective space after mandibular expansion and reduce buccal alveolar bone stress.

The efficacy and safety of acupuncture for perimenopausal insomnia: A protocol for a network meta-analysis.

BACKGROUND: As a common symptom of perimenopausal period, perimenopausal insomnia brings great pain to many women and families. Acupuncture has been accepted by people as the incidence rate of this disease increases. The purpose of this study is to systematically compare the safety and efficacy of various acupuncture treatments for perimenopausal insomnia through network meta-analysis. METHODS: We will search Web of Science, PubMed, The Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI), Wan Fang Date, VIP database, conference papers and grey literature. All relevant Randomized controlled trial (RCT) using acupuncture for perimenopausal insomnia will be included. Two reviewers will independently search and screen date. Network meta-analysis will be completed by Stata and WinBUGS software. RESULTS: This study will compare the efficacy and safety of different acupuncture treatments for perimenopausal insomnia. CONCLUSION: The result of this study will provide reliable evidence for evaluating the efficacy and safety of acupuncture in the treatment of perimenpausal insomnia. INPLASY REGISTRATION NUMBER: INPLASY2020110047.

Efficacy of different designs of mandibular expanders: A 3-dimensional finite element study.

INTRODUCTION: Nonsurgical mandibular expansion has been increasingly performed in recent years because it can effectively expand the mandibular dental arch. However, many types of mandibular expanders have been used in previous studies. No relevant studies have compared the biomechanical responses of different designs of mandibular expansion appliances with screws. Therefore, the purpose of this study was to analyze the stress distribution and displacement of the dentoalveolar structures according to different designs of mandibular screw expanders. METHODS: Cone-beam computed tomography scans were used for 3-dimensional reconstruction of the mandibular finite element model. Four different designs of mandibular expanders, 1 removable expander (type A) and 3 fixed expanders (types B, C, and D), were added to the finite element models. Expanders were activated transversely for 0.2 mm. The initial tooth displacement and von Mises stress distribution were evaluated. RESULTS: All the expanders enlarged the arch dimensions. In types A and B, the stress was mainly concentrated in the region of the anterior teeth, along with greater tooth displacement, whereas in types C and D, greater stress and displacement occurred in the region of the posterior teeth. Type A showed the greatest amount of transverse displacement. Type D was more efficient in the region of the posterior teeth. CONCLUSIONS: Types A and B should be used with great caution in the clinic because of their incompatible expansion pattern. Type D is the recommended mandibular expansion appliance because of its appropriate expansion pattern.

MicroRNA-107 is a novel tumor suppressor targeting POU3F2 in melanoma.

BACKGROUND: Melanoma is one of the major types of skin cancer. The metastatic melanoma is among the most lethal forms of malignant skin tumors. We hereby aimed to characterize a novel microRNA (miR) in the metastatic melanoma model. METHODS: First, we evaluated the expression of miR-107 in melanoma cells and tumor tissues. The comparison between primary and metastatic cancer tissues was also accessed. Next, we examined the impact of miR-107 on melanoma cell proliferation, cell cycle, colony formation, apoptotic activity, migration and matrix invasion. A downstream target of miR-107 was also predicted and validated functionally in melanoma cells. RESULTS: Our findings showed miR-107 was significantly downregulated in melanoma. Its expression was lowest in metastatic form. Over-expression of miR-107 reduced melanoma cell proliferation, migration and invasion. POU3F2 was identified as the downstream target of miR-107. Over-expression of POU3F2 antagonized miR-107-mediated inhibitory effect on melanoma cells. CONCLUSION: Our study has reported miR-107 as a novel tumor suppressive factor in the metastatic melanoma model. It has provided new avenue to manage melanoma and improve the survival rate in the advanced stage.

MicroRNA-107 is a novel tumor suppressor targeting POU3F2 in melanoma

BACKGROUND: Melanoma is one of the major types of skin cancer. The metastatic melanoma is among the most lethal forms of malignant skin tumors. We hereby aimed to characterize a novel microRNA (miR) in the metastatic melanoma model. METHODS: First, we evaluated the expression of miR-107 in melanoma cells and tumor tissues. The comparison between primary and metastatic cancer tissues was also accessed. Next, we examined the impact of miR-107 on melanoma cell proliferation, cell cycle, colony formation, apoptotic activity, migration and matrix invasion. A downstream target of miR-107 was also predicted and validated functionally in melanoma cells. RESULTS: Our findings showed miR-107 was significantly downregulated in melanoma. Its expression was lowest in metastatic form. Over-expression of miR-107 reduced melanoma cell proliferation, migration and invasion. POU3F2 was identified as the downstream target of miR-107. Over-expression of POU3F2 antagonized miR-107-mediated inhibitory effect on melanoma cells. CONCLUSION: Our study has reported miR-107 as a novel tumor suppressive factor in the metastatic melanoma model. It has provided new avenue to manage melanoma and improve the survival rate in the advanced stage.

A Network Pharmacology Approach to Determine the Active Components and Potential Targets of Curculigo Orchioides in the Treatment of Osteoporosis.

BACKGROUND Osteoporosis is a complex bone disorder with a genetic predisposition, and is a cause of health problems worldwide. In China, Curculigo orchioides (CO) has been widely used as a herbal medicine in the prevention and treatment of osteoporosis. However, research on the mechanism of action of CO is still lacking. The aim of this study was to identify the absorbable components, potential targets, and associated treatment pathways of CO using a network pharmacology approach. MATERIAL AND METHODS We explored the chemical components of CO and used the five main principles of drug absorption to identify absorbable components. Targets for the therapeutic actions of CO were obtained from the PharmMapper server database. Pathway enrichment analysis was performed using the Comparative Toxicogenomics Database (CTD). Cytoscape was used to visualize the multiple components-multiple target-multiple pathways-multiple disease network for CO. RESULTS We identified 77 chemical components of CO, of which 32 components could be absorbed in the blood. These potential active components of CO regulated 83 targets and affected 58 pathways. Data analysis showed that the genes for estrogen receptor alpha (ESR1) and beta (ESR2), and the gene for 11 beta-hydroxysteroid dehydrogenase type 1, or cortisone reductase (HSD11B1) were the main targets of CO. Endocrine regulatory factors and factors regulating calcium reabsorption, steroid hormone biosynthesis, and metabolic pathways were related to these main targets and to ten corresponding compounds. CONCLUSIONS The network pharmacology approach used in our study has attempted to explain the mechanisms for the effects of CO in the prevention and treatment of osteoporosis, and provides an alternative approach to the investigation of the effects of this complex compound.

Effects of Danggui-Shaoyao-San on the Influence of Spatial Learning and Memory Induced by Experimental Tooth Movement.

BACKGROUND: The pain caused by orthodontic treatment has been considered as tough problems in orthodontic practice. There is substantial literature on pain which has exactly effected on learning and memory; orthodontic tooth movement affected the emotional status has been showed positive outcomes. Danggui-Shaoyao-San (DSS) is a Traditional Chinese Medicine prescription that has been used for pain treatment and analgesic effect for orthodontic pain via inhibiting the activations of neuron and glia. We raised the hypothesis that DSS could restore the impaired abilities of spatial learning and memory via regulating neuron or glia expression in the hippocampus. METHODS: A total of 36 rats were randomly divided into three groups: (1) Sham group (n = 12), rats underwent all the operation procedure except for the placement of orthodontic forces and received saline treatment; (2) experimental tooth movement (ETM) group (n = 12), rats received saline treatment and ETM; (3) DSS + ETM (DETM) group (n = 12), rats received DSS treatment and ETM. All DETM group animals were administered with DSS at a dose of 150 mg/kg. Morris water maze test was evaluated; immunofluorescent histochemistry was used to identify astrocytes activation, and immunofluorescent dendritic spine analysis was used to identify the dendritic spines morphological characteristics expression levels in hippocampus. RESULTS: Maze training sessions during the 5 successive days revealed that ETM significantly deficits in progressive learning in rats, DSS that was given from day 5 prior to ETM enhanced progressive learning. The ETM group rats took longer to cross target quadrant during the probe trial and got less times to cross-platform than DETM group. The spine density in hippocampus in ETM group was significantly decreased compared to the sham group. In addition, thin and mature spine density were decreased too. However, the DSS administration could reverse the dendritic shrinkage and increase the spine density compared to the ETM group. Astrocytes activation showed the opposite trend in hippocampus dentate gyrus (DG). CONCLUSIONS: Treatment with DSS could restore the impaired abilities on ETM-induced decrease of learning and memory behavior. The decreased spines density in the hippocampus and astrocytes activation in DG of hippocampus in the ETM group rats may be related with the decline of the ability of learning and memory. The ability to change the synaptic plasticity in hippocampus after DSS administration may be correlated with the alleviation of impairment of learn and memory after ETM treatment.

Isolation and multiple differentiation potential assessment of human gingival mesenchymal stem cells.

The aim of this study was to isolate human mesenchymal stem cells (MSCs) from the gingiva (GMSCs) and confirm their multiple differentiation potentials, including the odontogenic lineage. GMSCs, periodontal ligament stem cells (PDLSCs) and dermal stem cells (DSCs) cultures were analyzed for cell shape, cell cycle, colony-forming unit-fibroblast (CFU-F) and stem cell markers. Cells were then induced for osteogenic and adipogenic differentiation and analyzed for differentiation markers (alkaline phosphatase (ALP) activity, mineralization nodule formation and Runx2, ALP, osteocalcin (OCN) and collagen I expressions for the osteogenic differentiation, and lipid vacuole formation and PPARγ-2 expression for the adipogenic differentiation). Besides, the odontogenic differentiation potential of GMSCs induced with embryonic tooth germ cell-conditioned medium (ETGC-CM) was observed. GMSCs, PDLSCs and DSCs were all stromal origin. PDLSCs showed much higher osteogenic differentiation ability but lower adipogenic differentiation potential than DSCs. GMSCs showed the medial osteogenic and adipogenic differentiation potentials between those of PDLSCs and DSCs. GMSCs were capable of expressing the odontogenic genes after ETGC-CM induction. This study provides evidence that GMSCs can be used in tissue engineering/regeneration protocols as an approachable stem cell source.

[Association between small ubiquitin-related modifier-1 gene polymorphism and non-syndromic oral clefting].

OBJECTIVE: To investigate the association between small ubiquitin-related modifier-1 (SUMO-1) gene rs6709162, rs7599810, rs7580433 polymorphism and non-syndromic oral clefting (NSOC). METHODS: Our study consisted of 208 Ningxia NSOC patients, their parents (189 fathers and 176 mothers), 172 nuclear families (patients and their parents), and 284 normal controls. DNA was extracted and polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) was used to identify rs6709162, rs7599810, rs7580433 genotypes of the samples. The data was analyzed by case-control analysis, family based associated test (FBAT), and transmission disequilibrium test (TDT). RESULTS: Case-control study found that TT genotype's frequency was significantly different in cleft lip and cleft palate group compared with the control group at rs7599810 of SUMO-1 (P=0.01, P=0.01). TDT test showed that rs7599810's T allele had over-transmitted (P=0.00) in cleft lip and palate group. FBAT analysis revealed that distribution of rs7599810's TT genotype and T allele was significantly different (P=0.00, P=0.00). TDT test showed that rs6709162's C allele in cleft palate and cleft lip and palate patients had over-transmitted (P=0.00, P=0.01). rs7580433's G allele in cleft lip group had over-transmitted (P=0.05). CONCLUSION: SUMO-1 gene polymorphism is associated with NSOC.

Association between MSX1 variants and oral clefts in Han Chinese in western China.

Previous animal and association studies have shown that the MSX1 gene is associated with oral clefts. Our aim was to investigate association between variants in the MSX1 gene and oral clefts in a Han Chinese population. Our study group consisted of 206 nonsyndromic oral cleft (NSOC) nuclear families (including the patients and their parents) and 224 controls. The three variants evaluated in this study were single-nucleotide polymorphisms rs3821949 and rs12532 and a missense mutation P147Q. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype the three markers. Case-control and family-based association analyses were carried out. In the case-control analysis, no significant differences in genotypic or allelic frequencies were observed in any of the two single-nucleotide polymorphisms between patients and controls. Although the homozygous T allele for P147Q was not detected in any sample in this population, heterozygotes were more prevalent in NSOC (1.2%) when compared with the controls (0%). The analyses for family-based association did not suggest association between any of the three variants and NSOC. No significant association was found between NSOC and rs3821949 or rs12532 in MSX1 gene, whereas an association was observed between the P147Q variant and cleft lip with cleft palate in the case-control analysis.

[Association between interferon regulatory factor 6 gene polymorphism and non-syndromic oral clefting].

OBJECTIVE: To investigate the association between interferon regulatory factor 6 (IRF6) gene polymorphism and non-syndromic oral clefting (NSOC). METHODS: Experimental group consisted of 186 Ningxia NSOC patients, their parents (183 fathers and 174 mothers), 172 core families (patient+parents), and control group consisted of 200 normal children. DNA was extracted and PCR-restriction fragment length polymorphism (PCR-RFLP) was used to identify the genotypes of the samples, case-control analyses and transmission-disequilibrium test (TDT) were carried out. RESULTS: Compared with control group, there were significant differences in both rs642961's and rs4844880's AA genotype and A allele among NSOC patients (P < 0.05), but no difference in cleft palate (P = 0.15, P = 0.967, respectively). In TDT analysis, the A allele of rs642961 had a strong over-transmission in NSOC (P < 0.05), so did the rs4844880'A allele (P < 0.05), but neither of them had significant difference in cleft palate (P = 0.91, P = 0.95, respectively). CONCLUSION: IRF6 gene polymorphism is associated with NSOC.

[Comparison of efficacy between nateglinide and repaglinide in treating type 2 diabetes: a randomized controlled double-blind clinical trial].

OBJECTIVE: To compare the efficacy of nateglinide with repaglinide in the treatment of type 2 diabetes mellitus. METHODS: Forty-six type 2 diabetic patients were randomly treated with repaglinide (group A, 1.0 mg tid, n=23) or nateglinide (group B, 90.0 mg tid, n=23). The trial consisted of a 4-week equilibrated period followed by 12 weeks of treatment course. RESULTS: In group A, the fasting blood glucose (FBG) and 30-, 60-, 120- min postprandial blood glucose (PBG), as well as hemoglobin A1c were decreased significantly (P<0.05). In group B, the 60-min and 120-min PBG decreased remarkably (P<0.05), but FBG, 30-min PBG and A1c decreased with no statistical significance (P>0.05). After 12 weeks treatment, the 30-, 60-, 120-min postprandial insulin level, area under the curve of insulin and C peptide (0 to 120 min) increased in both groups (P<0.05). No significant difference was found between the effects of repaglinide and nateglinide on early phase insulin secretion. CONCLUSION: The glucose lowering effect of repaglinide at a dosing level of 1.0 mg tid was better than that of nateglinide 90 mg tid on fasting blood glucose and A1c during 12 weeks treatment period, yet the insulinotropic effects of the two drugs were similar.

[The associations of HLA-DQB1 gene with onset age and autoantibodies in type 1 diabetes].

OBJECTIVE: To evaluate the associations of human leukocyte antigen (HLA) DQB1 gene with onset age and autoantibodies in type 1 diabetes mellitus(T1DM) in Chinese Han population in Sichuan area. METHODS: Forty-six type 1 diabetic patients and 52 healthy control subjects were involved in this study. HLA-DQB1 typing was performed by polymerase chain reaction-sequence specific primer(PCR-SSP). Glutamic acid decarboxylase antibody (GADA) and islet cell antibody (ICA) were qualitatively analyzed by enzyme linked immunosorbent assay (ELISA). RESULTS: The positive rate of DQB1*0201 was higher in T1DM than in controls (OR=18, P<0.005), but those of DQB1*0601, *0602 were higher in controls than in T1DM(OR=0.07, 0.31 respectively, both P<0.05).The positive rate of DQB1*0602 in type 1 diabetic patients with onset age>or=20 years was higher than that in the patients with onset age <20 years (P<0.05). GADA was more frequent in DQB1*0201(+) patients than in DQB1*0201 (-) patients (P<0.025). CONCLUSION: The findings show that DQB1*0201 is susceptible to T1DM, whereas DQB1*0601, *0602 are protective in Chinese Han population in Sichuan area. DQB1*0602 may delay the onset of T1DM. The positive rate of DQB1*0201 correlates positively with that of GADA.

[Gliquidon induced-desensitization of pancreatic beta cells and the partial reversion of responsiveness after the desensitization of exposure to drug in normal and STZ type 2 diabetic rats].

OBJECTIVE: To test if gliquidone (gli) induces beta cells desensitization as other sulfonylurea (Su) and the features of the reversion of responsiveness. METHODS: An obese type 2 diabetic (DM2) rat model was developed, for which low dose streptozocin (STZ, 25 mg/L) was injected i.p. into Wistar rats followed by high sucrose-fat diet feeding for 8 weeks as described previously. Islet cells from normal and DM2 rats were isolated and cultured over 24 h in a medium with or without gli and the static Ins secretion at various time intervals were measured by RIA. These islet cells either untreated or pre-treated for 24 h with various dosages of gli (500; 1000; 1500 ng/ml) were perifused by a column perifusion system. Ins release in response to the corresponding doses of gli was evaluated. RESULTS: Insulin secretion decreased remarkably under the static stimuli to DM2 islets, compared with that of the normal controls (P < 0.05). Insulin secretion in normal islets in response to 500 and 1000 ng/ml gli rose to a peak level at the second hour, and then declined with the time, but the islets did not respond to 1500 ng/ml gli. Gli pre-treated islets gave no response to acute gli stimuli. Short term (10 min) removal of the islets from gli-exposure could not reverse the responsiveness; however, after the exposure to gli being discontinued for 20 h, desensitization could be reverted completely in use of 500 ng/ml gli; partially in use of 1000 ng/ml gli; but not in use of 1500 ng/ml gli. CONCLUSION: The results indicated that the exposure of beta cell to gli at various concentrations induced selective desensitization of the beta cell to gli stimuli; and the desensitization could be reverted completely or partially after the exposure being discontinued for 20 h to 500 ng/ml and 1000 ng/ml but not to 1500 ng/ml gli, respectively. The restoration of the response of beta cell to gli stimuli was dose-dependent and time-dependent.