Research progress in prevention and treatment of repeated implantation failure by TCM compounds based on "Yu Pei Qi Sun" theory / 国际中医中药杂志

Women undergoing in vitro fertilization-embryo transfer (IVF-ET) may experience repeated implantation failure (RIF). Under the guidance of "Yu Pei Qi Sun" theory, Traditional Chinese Medicine (TCM) compounds can improve the quality of sperm and eggs of both husband and wife by anti-oxidative stress, improving mitochondrial function and reducing excessive apoptosis before IVF-ET to obtain high-quality embryos; TCM compounds can also promote angiogenesis, anti-oxidative stress, regulation of estrogen and progesterone receptor content, regulate immunity to improve female endometrial receptivity to facilitate embryo implantation; it can also invigorate the spleen and kidney after transplantation and caring for the fetus to help implantation, as well as alleviate the anxiety of patients during transplantation.

The Reference Values for Muscle Mass and Strength in Healthy Indian Adults Using Whole-Body Potassium Counter and Isokinetic Dynamometer

The study aims to define the sex‑based reference data for muscle mass and strength among healthy young Indians and to compare the data from the present study with available literature. Healthy Indian adults (n = 100) aged between 18 and 40 years were recruited. The assessment of muscle mass and strength was performed. The body cell mass (BCM), fat‑free mass, and muscle strength parameters were significantly higher among males compared to females (P < 0.001). A comparison of the current study data with the available literature showed that though BCM was comparable, Indians demonstrated a significantly lower isometric peak torque (P < 0.001 for both sexes). These findings suggest that Indians tend to have a lower muscle strength compared to the Western population, despite having a comparable BCM content.

Self-assembling, pH-responsive nanoflowers for inhibiting PAD4 and neutrophil extracellular trap formation and improving the tumor immune microenvironment

Self-assembling carrier-free nanodrugs are attractive agents because they accumulate at tumor by an enhanced permeability and retention (EPR) effect without introduction of inactive substances, and some nanodrugs can alter the immune environment. We synthesized a peptidyl arginine deiminase 4 (PAD4) molecular inhibitor, ZD-E-1M. It could self-assembled into nanodrug ZD-E-1. Using confocal laser scanning microscopy, we observed its cellular colocalization, PAD4 activity and neutrophil extracellular traps (NETs) formation. The populations of immune cells and expression of immune-related proteins were determined by single-cell mass cytometry. ZD-E-1 formed nanoflowers in an acidic environment, whereas it formed nanospheres at pH 7.4. Accumulation of ZD-E-1 at tumor was pH-responsive because of its pH-dependent differences in the size and shape. It could enter the nucleus and bind to PAD4 to prolong the intracellular retention time. In mice, ZD-E-1 inhibited tumor growth and metastasis by inhibiting PAD4 activity and NETs formation. Besides, ZD-E-1 could regulate the ratio of immune cells in LLC tumor-bearing mice. Immunosuppressive proteins like LAG3 were suppressed, while IFN-γ and TNF-α as stimulators of tumor immune response were upregulated. Overall, ZD-E-1 is a self-assembling carrier-free nanodrug that responds to pH, inhibits PAD4 activity, blocks neutrophil extracellular traps formation, and improves the tumor immune microenvironment.

Decidualization induced by mouse tetraploid embryos / 解剖学报

Objective To investigate the role of inner cell mass (ICM) in decidualization using decidua induced by two-cell embryos or tetraploid embryos through tubal embryo transfer. Methods Tetraploid embryo, as the inner cell mass-deficient embryo, were produced by electrofusion of mouse 2-cell embryos. Decidua was induced by 2-cell embryos or tetraploid embryos through tubal embryo transfer. Decidua induced by 2-cell embryos was employed as a control. Morphologic and implantation site of decidua were compared between two-cell embryo-induced decidua and tetraploid embryo-induced decidua. The differentially expressed microRNA ( miRNA ) was screened by high-throughput sequencing. The target genes of differentially expressed miRNA in two groups were screened for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Tetraploid embryo-induced decidual tissue and 2-cell embryo- induced decidual tissue were very similar at the implantation site, but there were significant differences in decidual morphology. There were 16 miRNAs differentially expressed in decidua of the two groups, of which 11 miRNAs (miR-466f- 3p, miR-302 d-3p, miR-466i-5p, miR-465c-5p, miR-302a-5p, miR-7068-3p, miR-741-3p, miR-302a-3p, miR-433-5p, miR-144-5p, miR-878-5p) were up-regulated in tetraploid embryo-induced decidua and 5 miRNAs (miR-690, miR-193b- 5p, miR-147-3p, novel_327, miR-363-3p) were down-regulated in tetraploid embryo-induced decidua. Bioinformatics analysis showed that the target genes played function such as protein binding and ion binding, and mainly involved in cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathway, estrogen signaling pathway, vascular endothelial growth factor (VEGF) signaling pathway and so on. Conclusion ICM plays an important role in decidualization.

Quantification ofβcell mass using18 F-FP-(+)-DTBZ, a vesicular monoamine transporter type 2 radiotracer:A longitudinal study in type 1 diabetic rats / 中华内分泌代谢杂志

Objective The aim of this study was to investigate the possibility of type 2 vesicular monoamine transporter molecular probe,18 F-FP-(+)-DTBZ, in the monitoring of total islet β cell mass in animal models. Methods Two groups of Wistar rats were included in this study. In the type 1 diabetes group ( n = 6 ) , the streptozotocin ( STZ) was intraperitoneally injected at a dose of 65 mg/kg, and the control group ( n= 6 ) was likewisely injected with an equal volume of saline, Micro- positron emission tomography ( PET )/ computed tomography ( CT) imaging was performed at these rats post injection of18 F-FP-(+)-DTBZ at 0. 5, 1, 4, 6, and 12 months after STZ or saline injection, bodyweight and glucose level were also measured. Results The average standardized uptake values ( SUV) in the pancreas in the type 1 diabetes rats were decreased significantly than that of the control group at 0.5, 1, and, 4 months ( P<0.05) , and there was no significant difference at 6th and 12th months ( P>0.05) post injection of STZ and saline. Fasting blood glucose positively correlated with pancreatic SUV in the two groups at 0.5, 1, and 4 months (P<0.05) post injection of STZ and saline. Conclusion 18F-FP-(+)-DTBZ PET imaging is a promising method for dynamic monitoringβcell mass in type 1 diabetic rats.

Cell Count of Mouse Blastocyst on Pre-clinical Evaluation of Safety of Medical Devices in Assisted Reproductive Technologies / 中国医疗器械杂志

Various types of medical devices used in assisted reproductive technologies (ART) should be detected for their safety by strict biological assays. Mouse embryo assay(MEA)has been recognized as one of the most important and standardized methods with the threshold more than 80% of blastocyst formation rate (BR) after 96 h culture of fertilized eggs. The disadvantage using BR for embryonic quality control has been concerned as it is ubiquitously dependent of embryonic morphology and the detailed data including molecular and genetic information is obviously missing and incomplete. This leads to the urgent requirement for more sensitive and efficient assessments for the quality control of ART. This study evaluated the reliability of an immunofluorescent MEA by counting total cell and differential number of the cells in the inner cell mass (ICM) and trophectoderm (TE) in the blastocyst. This method improved the traditional MEA, provided a sensitive and powerful platform to assess embryonic developmental viability and should be suggested as a standard assay to be globally used for the quality control of medical devices and pre-clinical procedures in ART.

Overall Blastocyst Quality, Trophectoderm Grade, and Inner Cell Mass Grade Predict Pregnancy Outcome in Euploid Blastocyst Transfer Cycles / 中华医学杂志(英文版)

<p><b>Background</b>Despite recent advances that have improved the pregnancy success rates that can be achieved via in vitro fertilization (IVF) therapy, it is not yet clear which blastocyst morphological parameters best predict the outcomes of single blastocyst transfer. In addition, most of the previous studies did not exclude the effect of embryo aneuploidy on blastocysts transfer. Thus, the present study investigated the predictive value of various parameters on the pregnancy outcomes achieved via the transfer of frozen euploid blastocysts.</p><p><b>Methods</b>The study retrospectively analyzed 914 single euploid blastocyst transfer cycles that were performed at the Peking University Third Hospital Reproductive Medical Center between June 2011 and May 2016. The expansion, trophectoderm (TE), and inner cell mass (ICM) quality of the blastocysts were assessed based on blastocyst parameters, and used to differentiate between "excellent", "good", "average", and "poor"-quality embryos. The relationship between these embryo grades and the achieved pregnancy outcomes was then analyzed via the Chi-square and logistic regression tests.</p><p><b>Results</b>For embryo grades of excellent, good, average and poor, the clinical pregnancy rates were 65.0%, 59.3%, 50.3% and 33.3%, respectively; and the live-birth rates were 50.0%, 49.7%, 42.3% and 25.0%, respectively. Both the clinical pregnancy rate (χ = 21.28, P = 0.001) and live-birth rate (χ = 13.50, P < 0.001) increased with the overall blastocyst grade. Both rates were significantly higher after the transfer of a blastocyst that exhibited either an A-grade or B-grade TE, and similarly, an A-grade ICM, than after the transfer of a blastocyst that exhibited a C-grade TE and/or ICM. The degree of blastocyst expansion had no apparent effect on the clinical pregnancy or live-birth rate. All odds ratio were adjusted for patient age, body mass index, length (years) of infertility history, and infertility type.</p><p><b>Conclusions</b>A higher overall euploid blastocyst quality is shown to correlate most strongly with optimal pregnancy outcomes. The study thus supports the use of the described TE and ICM morphological grades to augment current embryo selection criteria.</p>

Evaluation of β-cell mass in type 2 diabetic patients with 18F-FP-(+)-DTBZ,a vesicular monoamine transporter type 2 molecular probe / 中华内分泌代谢杂志

Objective The aim of this study was to evaluate theβ-cell mass ( BCM) in patients with type 2 diabetes mellitus( T2D) by PET/CT using [ 18 F]-FP-(+)-DTBZ, which is a vesicular monoamine transporter type 2 molecular probe. The feasibility of pancreatic head, body and tail as the target area was investigated for evaluation of the BCM in T2D. Methods 15 subjects ( 8 with T2D, and 7 as control) were involved in this study with 20 min static PET imaging at 40 min post injection of [ 18 F]-FP-(+)-DTBZ. The volume of interest ( VOIs) of pancreatic head, body and tail were drawn and quantitatively assessed. Spleens were collected as reference tissue for SUVR calculation. Results SUVR in the pancreatic head ( SUVR=1.72 ± 0.47) and pancreatic body, tail ( SUVR=1.85 ± 0.41) in T2D group was no significant difference, and no significant difference was observed in the pancreatic head (SUVR=2.54±0.57) and pancreatic body, tail(SUVR=2.73±0.41) in control group as well. In T2D group, a significant decreased SUVR was found in pancreatic head (P=0.0088) and pancreatic body and tail (P=0.0012) compared with controls. Conclusion The VMAT2 molecular probe [ 18 F]-FP-(+)-DTBZ can be used to evaluate BCM in patients with T2D.

Rapid cryopreservation for Siraitia grosvenorii cells based on cells' capacitance detection / 生物工程学报

A rapid quantitative evaluation method for Siraitia grosvenorii cells was successfully developed based on plant cells' capacitance value detected by a viable cell mass monitor and the cryopreservation of S. grosvenorii suspension cells was optimized. The survival rate of S. grosvenorii cells was quantitatively measured by viable cell mass monitor and 2, 3, 5-triphenyltetrazolium chloride (TTC). An optimum cryoprotectant recipe is that the growth medium contained 10% sucrose and 10% DMSO. The experimental results also showed higher cell survival rates and cell viabilities were achieved when suspension cells were treated with pretreatment of 0.2 mol/L sucrose. With the increase of concentration of sucrose, however, the cell survival rate was decreased. And the cell survival rate represented a bell shape with the increase of pretreatment time. The highest cell survival rate and cell viability were obtained with the 9 h' s pretreatment. In addition, there was a good correlation between the cell survival rate measured by cell recovery test and that measured by viable cell mass monitor, while there were no significant differences in the cell morphology and the ability of mogrosides V production by S. grosvenorii cells cultured in suspension after cryopreservation. Therefore, the evaluation method developed based on the viable cell mass monitor has good feasibility and reliability.

Parámetros de composición corporal en pacientes VIH mediante el análisis de la biompedancia eléctrica

Se han descrito cambios en la composición corporal en pacientes VIH mediante el análisis de la bioimpedancia eléctrica (ABE). Hay pocos estudios que describan estos cambios en la composición corporal en pacientes VIH en Venezuela. Objetivo: Conocer cuáles son las características de la composición corporal de los pacientes VIH (Hospitalizados y Ambulatorios), período enero - agosto 2015. Materiales y Métodos: Estudio descriptivo - transversal. Tres grupos: Hospitalizados: pacVIH-h (n=22), Ambulatorio: pacVIH-a (n=47) y No VIH: Control (n=28). Se registraron género, peso, talla y LCD4+. Mediante ABE se obtuvo: Masa grasa (MG), Tejido adiposo abdominal (TAA), Agua corporal total (ACT), Agua intracelular (AIC), Agua extracelular (AEC), Masa celular corporal (MCC), Masa libre de grasa (MLG), Potasio corporal total (KCT), Ángulo de Fase (AF). Resultados: Peso, IMC, LCD4+ fue menor en pacVIH-h. La MG y TAA fue menor en grupos de pacientes VIH con respecto al Control. No hubo diferencias en Agua Corporal. MMC fue menor en pacVIH-a. AF fue menor en pacVIH. Una correlación significativa entre MG y TAA, y LCD4+. Conclusión: Este estudio ha permitido exponer y reconocer los aspectos relacionados con los cambios en la composición corporal que ocurren en el paciente VIH adulto. La relación entre el compartimento graso y CD4+ permitiría explorar el papel del tejido adiposo en la reconstitución inmune.

Body composition in HIV patients have been assessed previously using bioelectrical impedance analysis (BIA). Lack of studies that describes changes in body composition in Venezuelan HIV patients. Objective: To assess body composition characteristic of HIV patients (hospitalized, ambulatory) , period January-August 2015. Methods: Descriptive-transversal study. Three groups: hospitalized: HIV-h (n=22), ambulatory: HIV-a (n=47) and Control (n=28). Gender, weight, height, CD4+ were measured. By BIA: Fat Mass (FM), Abdominal Adipose Tissue (AAT), Total body water (TBW), Intracellular water (ICW), Extracellular water (ECW), Body cell mass (BCM),Free Fat Mass (FFM), Total body potassium (TBK), Phase angle (PA). Results: Weight, BMI, CD4+ were lower in HIV-h. FM and AAT were lower in HIV patients. Water compartment showed no differences. BCM were lower in HIV-a. PA was lower in HIV patients. Significant relationship between FM, ATT and CD4+ was found. Conclusions: This study let us expose and recognize body composition changes that occur in HIV patients. Relationship between FAT, AAT and CD4+ can let us explore the possible role of adipose tissue in immune reconstitution.

The effect of the site of laser zona opening on the complete hatching of mouse blastocysts and their cell numbers / 대한생식의학회지

OBJECTIVE: We studied the effect of the site of laser zona opening on the complete hatching of mouse blastocysts and the cell numbers of the completely hatched blastocysts. METHODS: Mouse blastocysts were randomly allocated to the inner cell mass (ICM) group (zona opening performed at the site of the ICM, n=125), the trophectoderm (TE) group (zona opening performed opposite to the ICM, n=125) and the control group (no zona opening, n=125). RESULTS: The rate of complete hatching of the blastocysts was not significantly different in the ICM and the TE group (84.8% vs 80.8%, respectively; p=0.402), but was significantly lower in the control group (51.2%, p<0.001). The cell numbers in the completely hatched blastocysts were comparable in the control group, the ICM group, and the TE group (69±19.3, 74±15.7, and 71±16.8, respectively; p=0.680). CONCLUSION: These findings indicate that the site of laser zona opening did not influence the rate of complete hatching of mouse blastocysts or their cell numbers.

Mechanistic insights into pancreatic beta-cell mass regulation by glucose and free fatty acids / 대한해부학회지

Pancreatic islets are responsible for blood glucose homeostasis. Reduced numbers of functional (insulin-secreting) beta-cells in pancreatic islets underlies diabetes. Restoration of the secretion of the proper amount of insulin is a goal. Beta-cell mass is increased by neogenesis, proliferation and cell hypertrophy, and is decreased by beta-cell death primarily through apoptosis. Many hormones and nutrients affect beta-cell mass, and glucose and free fatty acid are thought to be the most important determinants of beta-cell equilibrium. A number of molecular pathways have been implicated in beta-cell mass regulation and have been studied. This review will focus on the role of the principle metabolites, glucose and free fatty acid, and the downstream signaling pathways regulating beta-cell mass by these metabolites.

Application of functional imaging in diagnosis of diabetes mellitus / 中华内分泌代谢杂志

In either type 1 or type 2 diabetes,there is significant loss of β cell mass.Understanding the changing of β cell mass in the course of diabetes would provide important information for diagnosis and treatment.Functional imaging like magnetic resonance imaging or positron emission tomography (PET) can provide safe and noninvasive detection of loss of β cell mass in the course of diabetes.Among them,radio-labelled imaging is the most sensitive imaging procedure of the β cell ; For dihydrotetrabenazine PET imaging aiming β cell mass,there has been some primary outcome.For the key factor causing type 2 diabetes,18 F-6-deoxy-6-fluoro-D-glucose (18F-6-FDG) PET imaging is an effective tracer to study the glucose transporting condition in vivo.Further development of functional imaging will be of great value in diagnosis and treatment of diabetes.

Enhancing effects of serum-rich and cytokine-supplemented culture conditions on developing blastocysts and deriving porcine parthenogenetic embryonic stem cells

The present study was conducted to develop an effective method for establishment of porcine parthenogenetic embryonic stem cells (ppESCs) from parthenogenetically activated oocyte-derived blastocysts. The addition of 10% fetal bovine serum (FBS) to the medium on the 3rd day of oocyte culturing improved the development of blastocysts, attachment of inner cell masses (ICMs) onto feeder cells, and formation of primitive ppESC colonies. ICM attachment was further enhanced by basic fibroblast growth factor, stem cell factor, and leukemia inhibitory factor. From these attached ICMs, seven ppESC lines were established. ppESC pluripotency was verified by strong enzymatic alkaline phosphatase activity and the expression of pluripotent markers OCT3/4, Nanog, and SSEA4. Moreover, the ppESCs were induced to form an embryoid body and teratoma. Differentiation into three germ layers (ectoderm, mesoderm, and endoderm) was confirmed by the expression of specific markers for the layers and histological analysis. In conclusion, data from the present study suggested that our modified culture conditions using FBS and cytokines are highly useful for improving the generation of pluripotent ppESCs.

Therapeutic Approaches for Preserving or Restoring Pancreatic beta-Cell Function and Mass

The goal for the treatment of patients with diabetes has today shifted from merely reducing glucose concentrations to preventing the natural decline in beta-cell function and delay the progression of disease. Pancreatic beta-cell dysfunction and decreased beta-cell mass are crucial in the development of diabetes. The beta-cell defects are the main pathogenesis in patients with type 1 diabetes and are associated with type 2 diabetes as the disease progresses. Recent studies suggest that human pancreatic beta-cells have a capacity for increased proliferation according to increased demands for insulin. In humans, beta-cell mass has been shown to increase in patients showing insulin-resistance states such as obesity or in pregnancy. This capacity might be useful for identifying new therapeutic strategies to reestablish a functional beta-cell mass. In this context, therapeutic approaches designed to increase beta-cell mass might prove a significant way to manage diabetes and prevent its progression. This review describes the various beta-cell defects that appear in patients with diabetes and outline the mechanisms of beta-cell failure. We also review common methods for assessing beta-cell function and mass and methodological limitations in vivo. Finally, we discuss the current therapeutic approaches to improve beta-cell function and increase beta-cell mass.

Islet Insulin Secretion, β-Cell Mass, and Energy Balance in a Polygenic Mouse Model of Type 2 Diabetes With Obesity

Abstract Type 2 diabetes (T2D) and obesity are polygenic metabolic diseases, highly prevalent in humans. The TALLYHO/Jng (TH) mouse is a polygenic model of T2D and obesity that encompasses many aspects of the human conditions. In this study, we investigated the key metabolic components including β-cell physiology and energy balance involved in the development of diabetes and obesity in TH mice. Glucose-stimulated insulin secretion from freshly isolated islets was significantly enhanced in TH mice compared with normal C57BL/6 (B6) mice, similar to the compensated stage in human T2D associated with obesity. This increased glucose responsiveness was accompanied by an increase in total β-cell mass in TH mice. Energy expenditure and locomotor activity were significantly reduced in TH mice compared with B6 mice. Food intake was comparable between the two strains but water intake was more in TH mice. Together, obesity in TH mice does not appear to be due to hyperphagia, and TH mice may be a genetic model for T2D with obesity, allowing study of the important signaling or metabolic pathways leading to compensatory increases in insulin secretion and β-cell mass in insulin resistance.

Silk fibroin hydrolysate exerts an anti-diabetic effect by increasing pancreatic beta cell mass in C57BL/KsJ-db/db mice

Components of silk including silk fibroin have long been used as anti-diabetic remedies in oriental medicine. However, detailed mechanisms underlying these anti-diabetic effects remain unclear. In this study, we examined the anti-diabetic activity of silk fibroin hydrolysate (SFH) in C57BL/KsJ-db/db (db/db) mice, a well-known animal model of non-insulin dependent diabetes mellitus. When the db/db mice were administered SFH in drinking water for 6 weeks, hyperglycemia in the animals gradually disappeared and the level of glycosylated hemoglobin decreased, indicating that SFH plays important role in reducing the symptoms of diabetes. In addition, SFH-treated db/db mice exhibited improved glucose tolerance with increased plasma insulin levels. Immunohistochemical and morphological analyses showed that SFH up-regulated insulin production by increasing pancreatic beta cell mass in the mice. In summary, our results suggest that SFH exerts anti-diabetic effects by increasing pancreatic beta cell mass in a non-insulin dependent diabetes mellitus mouse model.

A close association of body cell mass loss with disease activity and disability in Chinese patients with rheumatoid arthritis

OBJECTIVES: To investigate the association of body cell mass loss with disease activity and disability in rheumatoid arthritis patients. INTRODUCTION: Rheumatoid cachexia, defined as the loss of body cell mass, is important but under-recognized and contributes to morbidity and mortality in patients with rheumatoid arthritis. METHODS: One hundred forty-nine rheumatoid arthritis patients and 53 healthy, non-rheumatoid arthritis control subjects underwent anthropometric measurements of body mass index and waist and hip circumferences. Bioelectrical impedance analysis was used to determine the subjects' body compositions, including fat mass, skeletal lean mass, and body cell mass. The disease activity of rheumatoid arthritis was assessed using C-reactive protein serum, the erythrocyte sedimentation rate and the 28-joint disease activity score, while disability was evaluated using a health assessment questionnaire. RESULTS: Rheumatoid arthritis patients had lower waist-to-hip ratio (0.86 ± 0.07 vs. 0.95 ± 0.06; p<0.001) and lower skeletal lean mass indexes (14.44 ±1.52 vs. 15.18 ± 1.35; p = 0.002) than those in the healthy control group. Compared with rheumatoid arthritis patients with higher body cell masses, those with body cell masses lower than median had higher erythrocyte sedimentation rates (40.10 ± 27.33 vs. 25.09 ± 14.85; p<0.001), higher disease activity scores (5.36 ± 3.79 vs. 4.23 ± 1.21; p = 0.022) and greater disability as measured by health assessment questionnaire scores (1.26 ± 0.79 vs. 0.87 ± 0.79; p = 0.004). CONCLUSIONS: The loss of body cell mass is associated with higher disease activity and greater disability in rheumatoid arthritis patients. Body composition determined by bioelectrical impedance analysis can provide valuable information for a rheumatologist to more rapidly recognize rheumatoid cachexia in rheumatoid arthritis patients.

Reduced pancreatic β-cell mass is associated with decreased FoxO1 and Erk1/2 protein phosphorylation in low-protein malnourished rats

A low-protein diet leads to functional and structural pancreatic islet alterations, including islet hypotrophy. Insulin-signaling pathways are involved in several adaptive responses by pancreatic islets. We determined the levels of some insulin-signaling proteins related to pancreatic islet function and growth in malnourished rats. Adult male Wistar rats (N = 20 per group) were fed a 17 percent protein (normal-protein diet; NP) or 6 percent protein (low-protein diet; LP), for 8 weeks. At the end of this period, blood glucose and serum insulin and albumin levels were measured. The morphometric parameters of the endocrine pancreas and the content of some proteins in islet lysates were determined. The β-cell mass was significantly reduced (≅65 percent) in normoglycemic but hypoinsulinemic LP rats compared to NP rats. Associated with these alterations, a significant 30 percent reduction in insulin receptor substrate-1 and a 70 percent increase in insulin receptor substrate-2 protein content were observed in LP islets compared to NP islets. The phosphorylated serine-threonine protein kinase (pAkt)/Akt protein ratio was similar in LP and NP islets. The phosphorylated forkhead-O1 (pFoxO1)/FoxO1 protein ratio was decreased by 43 percent in LP islets compared to NP islets (P < 0.05). Finally, the ratio of phosphorylated-extracellular signal-related kinase 1/2 (pErk1/2) to total Erk1/2 protein levels was decreased by 71 percent in LP islets compared to NP islets (P < 0.05). Therefore, the reduced β-cell mass observed in LP rats is associated with the reduction of phosphorylation in mitogenic-related signals, FoxO1 and Erk proteins. The cause/effect basis of this association remains to be determined.

The new treatment target of diabetes: islet β-cell mass / 中华内分泌代谢杂志

Pancreatic islet β-cell mass is regulated by β-cell replication, nengenesis, apnptosis and cell size. β-cetl mass in diahetic patients is conspicuously less than that in normal subjects. Induction of β-cell regeneration and inhibition of β-cell apoptosis is the new target of diabetes treatment.