Study on the mechanism of improving islet β-cell function in patients with type 2 diabetes mellitus by Alogliptin benzoate / 中国糖尿病杂志

Objective To investigate the effect of Alogliptin benzoate on the serum autophagy markers in type 2 diabetes mellitus(T2DM)patients.Methods Eighty newly diagnosed T2DM patients who visited the Department of Endocrinology in Baoding No.1 Central Hospital from December 2021 to October 2022 were randomly divided into a group treated with Metformin(Met group,n=40)and a group treated with Met and Alog(Met+Alog group,n=40).The differences in BMI,WHR,FPG,HbA1c,Atg7 and Beclin-1 between two groups before and after 12 weeks of treatment were compared.Results After treatment,the levels of Atg7 and Beclin-1 increased in both groups(P<0.05),while FPG,HbA1c and HOMA-IR decreased(P<0.05).After treatment,Atg7,Beclin-1 and HDL-C in Met+Alog group were higher than those in Met group(P<0.05).Pearson correlation analysis showed that Atg7 was negatively correlated with BMI,FPG and HbA1c(P<0.05);Beclin-1 was positively correlated with HDL-C(P<0.05),and negatively correlated with BMI,FPG,HbA1c,and TG(P<0.05).Meta linear regression analysis showed that BMI was the influencing factor of Atg7,while BMI and HDL-C were the influencing factors of Beclin-1.Conclusion Alogliptin benzoate may improve islet β cell function by up-regulating the expression of autophagy related factors Atg7 and Beclin-1 in patients with T2DM.

Research progress in the mechanism of stimulator of interferon genes in type 2 diabetes mellitus and its microvascular complication / 中国糖尿病杂志

Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease that can lead to the damage of multiple tissues and organs throughout the body.Stimulator of interferon genes(STING)is an endoplasmic reticulum membrane protein that acts as an indirect cytoplasmic DNA sensor.The activation of the STING signaling pathway may be involved in T2DM and its microvascular complications through various mechanisms.This article reviews the research progress in the mechanism of STING in T2DM and its microvascular complications.

Jiedu Tongluo Tiaogan Prescription Protects Pancreatic β Cell by Targeting NLRP3 Inflammasome via TGR5/cAMP Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of Jiedu Tongluo Tiaogan prescription （JTTP） in protecting pancreatic β cells by targeting the bile acid Takeda G protein-coupled receptor 5 （TGR5）/cyclic adenosine monophosphate （cAMP） signaling pathway against NOD-like receptor protein 3 （NLRP3） inflammasome. MethodThirty-two male SPF-grade db/db mice were randomly divided into the model group， low-dose JTTP group （3.6 g·kg-1）， high-dose JTTP group （7.2 g·kg-1）， and metformin group （0.2 g·kg-1）. Eight db/m mice were assigned to the blank control group. The mice were treated with drugs for 8 weeks， and fasting blood glucose （FBG） was measured every 2 weeks. Oral glucose tolerance tests （OGTT） were conducted after the last administration. Enzyme-linked immunosorbent assay （ELISA） was performed to detect fasting insulin （FINS）， and the homeostasis model assessment of β-cell function （HOMA-β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β levels were calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in mouse pancreatic tissue. Immunofluorescence was performed to detect insulin expression in mouse pancreatic tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of proteins and mRNAs of key targets in the TGR5/cAMP signaling pathway and NLRP3 inflammasome. ResultCompared with blank group， FBG， OGTT， FINS， IL-6， TNF-α and IL-1β in model group were significantly increased （P<0.01）. Compared with model group， after 6 weeks of drug treatment， FBG level in JTTP group and metformin group decreased significantly （P<0.01）. The results of OGTT experiment showed that compared with model group， the blood glucose levels of mice in each administration group were decreased at all time points （P<0.05， P<0.01）， and the levels of FINS， TNF-α and IL-6 in JTTP dose groups and metformin group were significantly decreased. The level of IL-1β in JTTP high-dose group and metformin group was significantly decreased （P<0.01）. Pancreatic pathology showed that the islets in the model group were irregular in shape， uneven in distribution， and showed signs of atrophy. The prognosis of JTTP was that the cell count increased and the boundary was clearer. Immunofluorescence results showed that the islet cells in the blank group were arranged in an orderly and full shape with appropriate insulin secretion， while the islet cells in model group were distorted in shape， atrophy in structure and less insulin secretion. The insulin content of mice in JTTP and metformin group was significantly increased. Compared with blank group， mRNA expressions of NLRP3， apoptosis-related spot-like protein （ASC） and Caspase-1 in pancreatic tissues of model group were significantly increased （P<0.01）. Compared with model group， JTTP high-dose group and metformin group promoted the up-regulation of TGR5 and cAMP mRNA， and down-regulated the mRNA expressions of NLRP3， ASC and Caspase-1 （P<0.05， P<0.01）. Compared with blank group， the expression of TGR5 protein in model group was significantly decreased （P<0.01）. Compared with model group， TGR5 protein in JTTP high-dose group and metformin group was significantly increased （P<0.01）.

Role of METTL3 in homocysteine-induced autophagy in mouse islet beta cells / 中国组织工程研究

BACKGROUND:Hyperhomocysteinemia is closely related to the function of islet β cells,but its specific molecular mechanism is not fully understood. OBJECTIVE:To investigate the role of N6 methyltransferase-like 3(METTL3)in homocysteine(Hcy)-induced autophagy of mouse islet β cells. METHODS:The 3rd and 4th generation mouse islet β cells were taken for the experiment.(1)Cell modeling and grouping:cells in control group were not treated with Hcy,while those in homocysteine group were treated with 100 μmol/L Hcy for 48 hours.(2)The mouse islet β-cells were transfected with the plasmids overexpressing Ad-METTL3 and si-METTL3 according to the instructions of LipofectamineTM 2000.Three different interfering fragments were designed,and the one with the best interfering efficiency was verified and screened by PCR.(3)After transfection,the cells were divided into control group,Hcy group,Ad-NC(negative control)+Hcy group,Ad-METTL3+Hcy group,si-NC(negative control)+Hcy group and si-METTL3+Hcy group.(4)qRT-PCR and western blot were used to detect the expression levels of METTL3 and autophagy-related proteins LC3Ⅱ/Ⅰ and p62 in cells.Insulin level was determined by ELISA to evaluate insulin secretion capacity of islet cells.Autophagy-related proteins and insulin level were detected after overexpression and interference with METTL3. RESULTS AND CONCLUSION:Compared with the control group,the expression level of LC3Ⅱ/Ⅰ was increased(P＜0.05),the expression of p62 was significantly reduced(P＜0.05),and the insulin secretion capacity was significantly decreased(P＜0.05)in the Hcy group.Compared with the control group,the protein and mRNA levels of METTL3 were reduced in the Hcy group(P＜0.05).After METTL3 silencing in islet β cells,Hcy further upregulated the expression of LC3Ⅱ/Ⅰ(P＜0.05),significantly dowregulated the expression of p62(P＜0.05),and increased the insulin level(P＜0.05).After overexpression of METTL3,Hcy significantly decreased the LC3Ⅱ/Ⅰ expression and increased the p62 expression in islet β cells(P＜0.05).To conclude,METTL3 is involved in the Hcy-induced autophagy regulation of islet β cells and plays a role in the regulation of insulin secretion.

Role of non-coding RNA and exosomes in pathogenesis of gestational diabetes mellitus and their early diagnostic value / 中国组织工程研究

BACKGROUND:In recent years,there have been many studies on the mechanism of exosomal non-coding RNA in gestational diabetes mellitus,but there is a lack of the latest systematic review of exosomes from different sources,especially placental sources. OBJECTIVE:To summarize the changes and potential roles of microRNA(miRNA),long non-coding RNA(lncRNA),circular RNA(circRNA),and exosomes in gestational diabetes mellitus to provide potential targets for early screening and treatment of clinical gestational diabetes mellitus. METHODS:A literature search was conducted on PubMed,Web of Science,China National Knowledge Infrastructure,WanFang Data,and VIP databases to retrieve relevant articles on non-coding RNA or exosomal non-coding RNA in relation to gestational diabetes mellitus.A total of 74 articles were included for review. RESULTS AND CONCLUSION:(1)Non-coding RNAs play important pathological and physiological roles in the lifecycle activities,and increasing evidences suggest that non-coding RNAs are involved in the occurrence and development of gestational diabetes mellitus by regulating various physiological functions.This provides a new direction for the research of gestational diabetes mellitus.(2)Exosomes are widely present in the human body.Various cells can secrete exosomes,such as red blood cells,epithelial cells,and placental cells.Non-coding RNAs found in exosomes from different sources have been demonstrated to play a role in the pathogenesis,diagnosis,and treatment of gestational diabetes mellitus.(3)MiRNA and gestational diabetes mellitus:The role of peripheral blood miRNA in gestational diabetes mellitus is mainly to affect the functions of trophoblast cells,pancreatic beta cells and blood glucose levels in gestational diabetes mellitus;placental miRNA can reflect the severity of gestational diabetes and impair the function of trophoblast cells.(4)LncRNA and gestational diabetes mellitus:Peripheral blood lncRNA can induce insulin resistance through the phosphatidylinositol 3-kinase/protein kinase B pathway and may provide new insights for the diagnosis and treatment of gestational diabetes mellitus;placental lncRNA can regulate proliferation and migration of placental trophoblast cells,promoting the occurrence and development of gestational diabetes mellitus.(5)CircRNA and gestational diabetes mellitus:Peripheral blood and placental circRNA can induce the occurrence and development of gestational diabetes mellitus by impairing the proliferation,migration and metabolism of placental trophoblast cells.(6)Non-coding RNA in exosomes and gestational diabetes mellitus:Peripheral blood non-coding RNA in exosomes can affect gestational diabetes mellitus blood glucose levels and glucose homeostasis,and participate in the occurrence and development of gestational diabetes mellitus by influencing placental function.(7)Non-coding RNA has the potential to serve as biomarkers for early diagnosis of gestational diabetes mellitus.Additionally,engineered exosomes can better achieve targeted therapy for gestational diabetes mellitus.These latest findings provide a reference for both basic research and clinical translation of gestational diabetes mellitus.(8)In the future,improvements in the extraction and purification methods of peripheral blood exosomes should be improved,and factors such as race,diet and physical activity should be excluded to improve the reproducibility of results.Further prospective clinical studies are required to explore the clinical application of circulating non-coding RNA and exosomes in the prediction and diagnosis of gestational diabetes mellitus.

Interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes / 中国药房

OBJECTIVE To study the interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes. METHODS In vitro ferroptosis model was established in pancreatic β cells of mice by using high glucose. The effects of low-dose and high-dose 1，8-cineole （0.25， 0.5 μmol/L） on the level of Fe2+ in pancreatic β cells were investigated. The effects of 1，8-cineole （0.5 μmol/L） combined with ferroptosis inducer Erastin （20 μmol/L） and ferroptosis inhibitor Ferrostatin-1 （20 μmol/L） on the protein expressions of glutathione peroxidase-4 （GPX4） and cyclooxygenase-2 （COX2） were also detected. The type 2 diabetes model mice were established by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The effects of low-dose and high-dose 1，8-cineole （50， 200 mg/kg） on the pathological morphology of pancreatic tissue， the content of iron as well as the protein expressions of GPX4 and COX2 were investigated. RESULTS The results of the cell experiment showed that compared with the model group， pretreatment with 1，8-cineole significantly reduced intracellular Fe2+ levels and upregulated GPX4 protein expression， while downregulated COX2 protein expression in pancreatic β cells （P＜0.05）. After combining with Ferrostatin-1， the expression trends of the above two proteins were the same， while there was no statistically significant difference after combining with Erastin. The results of animal experiments showed that compared with the model group， after intervention with 1，8-cineole， the structure of the pancreatic islets in mice recovered intact and their morphology improved； the iron content of pancreatic tissue and protein expression of COX2 were decreased significantly （P＜0.05）， while protein expression of GPX4 was increased significantly （P＜0.05）. CONCLUSIONS 1，8-cineole could ameliorate pancreatic β cell injury induced by diabetes， the mechanism of which may be related to reducing intracellular iron deposition and regulating ferroptosis-related proteins.

JNK inhibitor SP600125 inhibits interleukin-1β induced pyroptosis in βTC-6 cells / 中华内分泌代谢杂志

Objective:To investigate whether interleukin(IL)-1β is involved in pyroptosis which leads to mouse islet β cell line βTC-6 cell damage, and to explore the role of JNK inhibitor SP600125 in inhibiting IL-1β induced βTC-6 cell pyroptosis.Methods:βTC-6 cell line and mouse islets were incubated with IL-1β for 48 h or intervened with both JNK inhibitor SP600125 and IL-1R antagonist IL-1Ra, then GSDMD expression and β cell pyroptosis morphology were detected by immunofluorescence staining of GSDMD and DAPI. The expression levels of Gsdmd, IL-1β and IL-18 mRNAs were detected by real time fluorescence PCR, and apoptosis was examined by Annexin-V/7-AAD staining combined with flow cytometry.Results:βTC-6 cell pyroptotic body was significantly increased in the IL-1β treated group compared with the control group, and the expressions of pyroptosis related genes Gsdmd, IL-1β, and IL-18 mRNA were significantly higher( P<0.05), and apoptosis was increased, suggesting that IL-1β effectively induced the βTC-6 cell pyroptosis, IL-1Ra prevented IL-1β induced βTC-6 cell pyroptosis. In the presence of JNK inhibitor SP600125, IL-1β treatment failed to induce the expressions of Gsdmd and IL-18 mRNA, markers of pyroptosis, and reduced the rate of apoptosis, indicating that SP600125 suppressed IL-1β induced βTC-6 cell pyroptosis. Conclusion:Pyroptosis is one of the mechanisms of βTC-6 cell impairment caused by IL-1β, and SP600125, a JNK inhibitor, can block the IL-1β induced pyroptosis pathway and has a potential role in inhibiting βTC-6 cell pyroptosis.

Cellular senescence and type 2 diabetes / 中华内分泌代谢杂志

Cellular senescence is a state in which cells enter permanent cell cycle arrest, which is characterized by senescence-associated secretory phenotype secretion, macromolecular damage, metabolic dysregulation and so on. Recent studies have shown a close relationship between cellular senescence and type 2 diabetes. On the one hand, the glycolipotoxic microenvironment of type 2 diabetes can accelerate cell senescence and accumulation. On the other hand, cellular senescence can promote the development of type 2 diabetes. For example, senescence of pancreatic β-cells leads to β-cell dysfunction and adipocytes senescence results in the secretion of pro-inflammatory cytokines, causing disturbances in lipid metabolism and exacerbating insulin resistance. Moreover, senescence of endothelial cells, retinal endothelial cells, and other cell types contributes to the occurrence of chronic complications in diabetes. Cellular senescence is not only an important factor in the onset of type 2 diabetes but also a consequence of its progression. Targeting cellular senescence holds promise as a new strategy for the treatment of type 2 diabetes.

Inhibitory effects of a TRPM4 inhibitor 9-phenanthrol on electrical activity of INS-1 pancreatic β-cells / 药学学报

The Ca2+-activated monovalent cation selective transient receptor potential melastatin 4 (TRPM4) channel expressed in pancreatic β-cells is implicated in the β-cell function and insulin secretion, but how pharmacological function of TRPM4 channel affects membrane excitability of β-cells remains largely unknown. Here, we report that pharmacological inhibition of TRPM4 by specific inhibitor 9-phenanthrol attenuates electrical activities of pancreatic β-cells. In whole-cell current clamp recordings, 9-phenanthrol results in inhibition of action potential frequency induced by tolbutamide of the INS-1 pancreatic β-cells in a dose-dependent manner with an IC50 value of 14.99 ± 7.93 μmol·L-1. Similarly, 9-phenanthrol also inhibited action potential firing in INS-1 cells stimulated by current injection. Further recordings of β-cells demonstrate the significant inhibitory effects on action potential peak and action potential amplitude by 9-phenanthrol. Taken together, our results show the involvement of TRPM4 channel function in pancreatic β-cells depolarization and action potential, it provides pharmacological experimental methods and theoretical support for the study of TRPM4 channel in pancreatic β-cells.

Pancreatic β-cell dedifferentiation detected by flow cytometry / 中华内科杂志

Objective:To establish a method for detecting pancreatic β-cell dedifferentiation using flow cytometry.Methods:Experimental study. Min6 (mouse β cell line), αTC1-6 (mouse α cell line), HepG2 (human hepatocellular carcinoma cells) and mouse F9 cells (mouse teratocarcinoma cell) were cultured with conventional medium. Min6 cells were treated with interleukin-1β (IL-1β) in combined with tumor necrosis factor α (TNFα), or palmitic acid (PA) overnight and stained with anti-chromogranin A (ChgA), anti-insulin (Ins), anti-glucagon (Gcg), anti-SRY-box transcription factor 9 (Sox9) and anti-octamer binding transcription factor 4 (Oct4) antibodies, respectively. Flow cytometry was applied to detect the pression of ChgA, Ins, Gcg, Sox9, and Oct4 in the cells, respectively. Unpaired Student t test was used for statistical analysis. Results:Flow cytometry analyses showed that Ins and ChgA were highly expressed in Min6 cells, Gcg was highly expressed in αTC1-6, Sox9 was highly expressed in HepG2, and Oct4 was highly expressed in F9 cells, respectively (around 90%). Treatment of Min6 cells with IL-1β+TNFα significantly decreased Ins positive staining cells (92.775%±1.702% vs. 97.125%±0.246%, P=0.045), while increased Sox9 positive staining cells (41.675%±0.390% vs. 25.875%±3.348%, P=0.003). No significant changes in ChgA and Oct4 expression could be viewed (both P>0.05). PA treatment elevated the number of Gcg positive staining cells (54.500%±3.597% vs. 41.160%±3.007%, P=0.022). The levels of mRNA expression by qPCR of the above proteins were in consistent with the levels of protein expression by flow cytometry in Min6 cells. Conclusion:Flow cytometry can be used to detect proteins expressed in dedifferentiated models of β cells, which provides a new method for identify dedifferentiation of pancreatic β cells.

Islet organoid as a promising model for diabetes

Studies on diabetes have long been hampered by a lack of authentic disease models that, ideally, should be unlimited and able to recapitulate the abnormalities involved in the development, structure, and function of human pancreatic islets under pathological conditions. Stem cell-based islet organoids faithfully recapitulate islet development in vitro and provide large amounts of three-dimensional functional islet biomimetic materials with a morphological structure and cellular composition similar to those of native islets. Thus, islet organoids hold great promise for modeling islet development and function, deciphering the mechanisms underlying the onset of diabetes, providing an in vitro human organ model for infection of viruses such as SARS-CoV-2, and contributing to drug screening and autologous islet transplantation. However, the currently established islet organoids are generally immature compared with native islets, and further efforts should be made to improve the heterogeneity and functionality of islet organoids, making it an authentic and informative disease model for diabetes. Here, we review the advances and challenges in the generation of islet organoids, focusing on human pluripotent stem cell-derived islet organoids, and the potential applications of islet organoids as disease models and regenerative therapies for diabetes.

ALDH1A3 + INS + cells in non-diabetic subjects and risk for type 2 diabetes: Analysis of cross-sectional data / 中华内分泌代谢杂志

Objective:To investigate the correlations of β cell dedifferentiation in non-diabetic subjects with risk factors for type 2 diabetes mellitus(T2DM).Methods:Immunofluorescence staining with insulin and β cell dedifferentiated marker ALDH1A3 was used to evaluate the β cell dedifferentiation levels in 38 non-diabetic and 23 T2DM. Correlation analyses were performed between β cell dedifferentiation levels and available clinical parameters including age, body mass index, HbA 1C level, triglycerides, and cholesterol levels in non-diabetic subjects. Results:β cell dedifferentiation level defined by the positive expression of ALDH1A3 in β cells(ALDH1A3 + INS + cell proportion) was significantly elevated in T2DM subjects( P<0.001). In PreD subjects, ALDH1A3 + INS + cells proportion were decreased( P=0.050) and negatively correlated with HbA 1C( r=-0.44, P=0.006), but not with age and body mass index. The analysis of correlation with lipidemic parameters showed that ALDH1A3 + INS + cells proportion was positively correlated with plasma total cholesterol level( r=0.39, P=0.045), but not plasma total triglyceride. Conclusion:ALDH1A3 + INS + cells were found to be decreased in prediabetes, suggesting that there may be enhanced β-cell identity in prediabetes to compensate for insulin secretion requirements; ALDH1A3 + INS + cells were elevated in people with high plasma total cholesterol levels, suggesting that total cholesterol may be one of the factors that induce β-cell dedifferentiation.

Icariin Inhibits Proliferation of CLC5 Hepatoma Cells via Akt/GSK3β/CDK Pathway / 中国实验方剂学杂志

ObjectiveTo study the effect of icariin on the proliferative capacity of hepatocellular carcinoma cell line CLC5 and the underlying mechanism. MethodThe targets of icariin were screened out by network pharmacology， and the target network and protein-protein interaction （PPI） network were constructed to predict the possible targets and pathways of icariin. CCK-8 assay was employed to explore the effects of different concentrations （0， 6.25， 12.5， 25， 50 μmol·L-1） of icariin on the viability of CLC5 cells. Further， CLC5 cells were treated with 0， 25， 50 μmol·L-1 icariin， and the effect of icariin on CLC5 cell proliferation was examined by Edu-488 assay and clone formation assay （CFA）. Western blot was employed to measure the expression levels of proteins in the protein kinase B （Akt）/glycogen synthase kinase 3β （GSK3β）/cell cycle-dependent kinase （CDK） pathway in the CLC5 cells exposed to different concentrations of icariin. ResultNetwork pharmacological analysis revealed that icariin may inhibit the hepatocellular carcinoma via cell cycle arrest and inhibition of tumor cell proliferation. Compared with the blank group， icariin decreased the viability of CLC5 cells in a time- and concentration-dependent manner （P<0.01） and reduced the positive rate of Edu-488 and the colonies in CFA （P<0.05， P<0.01）. Moreover， icariin down-regulated the protein levels of p-Akt， p-GSK3β， CDK4， and CyclinD1 （P<0.05， P<0.01）. ConclusionIcariin may block cell cycle to suppress the proliferation of CLC5 cells via inhibiting the Akt/GSK3β/CDK pathway.

Mechanism of compound Fufangteng mixture-containing serum in promoting proliferation of bone marrow mesenchymal stem cell / 器官移植

Objective To investigate the effect of compound Fufangteng mixture-containing serum on the proliferation of bone marrow mesenchymal stem cell (BMSC) and its mechanism. Methods Rat BMSC were isolated, cultured and purified in vitro by direct adherence method. Cell morphology was observed. Surface markers were identified by flow cytometry. The rats were treated with compound Fufangteng mixture at a dose of 3 mL/(kg·d) by gavage for 14 d, and then the drug-containing serum was collected. BMSC were divided into the blank control group, drug-containing serum group, Notch1 small interfering ribonucleic acid (siRNA) group and Notch1 siRNA+drug-containing serum group. The proliferation rate of BMSC was detected and the relative expression levels of Notch1 signaling pathway-associated messenger ribonucleic acid (mRNA) and proteins were measured in each group. Results Microscopic observation showed that the first generation BMSC were seen in the long spindle shape, and grown in the parallel or spiral pattern. The third generation BMSC positively expressed CD90 and CD44, whereas were negative for CD45. Compared with the blank control group, the proliferation rate of BMSC in the drug-containing serum group and Notch1 siRNA+ drug-containing serum group was significantly increased, whereas that of BMSC was significantly decreased in the Notch1 siRNA group (all P < 0.05). Compared with the Notch1 siRNA group, the proliferation rate of BMSC was significantly increased in the Notch1 siRNA+drug-containing serum group (P < 0.05). Compared with the blank control group, the relative expression levels of Hey1 and Delta-like ligand (DLL)1 mRNA and proteins were significantly up-regulated in the drug-containing serum group, whereas those were significantly down-regulated in the Notch1 siRNA group and Notch1 siRNA+drug-containing serum group (all P < 0.05). Compared with the Notch1 siRNA group, the relative expression levels of Hey1 and DLL1 mRNA and proteins were significantly up-regulated in the Notch1 siRNA+drug-containing serum group (all P < 0.05). Conclusions Compound Fufangteng mixture-containing serum may promote the proliferation of rat BMSC, and its mechanism is probably associated with the activation of Notch1 signaling pathway.

Investigation on the mechanism of acupuncture in treatment of diabetes mellitus type 2 based on the network of islet macrophages-pancreatic adipose cells-islet β cells / 中国针灸

To explore the possible new mechanism of acupuncture in the treatment of diabetes mellitus type 2 (T2DM) based on the islet inflammatory response. Islet macrophages, pancreatic adipose cells and islet β cells all participate in the pathogenesis of T2DM, and the three could form a network interaction. Acupuncture could regulate the functional phenotype of islet macrophages, improve the ectopic deposition of pancreatic adipose and repair the function of islet β cells, and play a unique advantage of overall regulation. It is suggested that acupuncture can be a potential treatment strategy for T2DM.

Reduced glycodeoxycholic acid levels are associated with negative clinical outcomes of gestational diabetes mellitus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Gestational diabetes mellitus (GDM) is characterized by glycemia and insulin disorders. Bile acids (BAs) have emerged as vital signaling molecules in glucose metabolic regulation. BA change in GDM is still unclear, which exerts great significance to illustrate the change of BAs in GDM. GDM patients and normal pregnant women were enrolled during the oral glucose tolerance test (OGTT) screening period. Fasting serums were sampled for the measurement of BAs. BA metabolism profiles were analyzed in both pregnant women with GDM and those with normal glucose tolerance (NGT). Delivery characteristics, delivery gestational age, and infant birthweight were extracted from medical records. GDM patients presented distinctive features compared with NGT patients, including higher body mass index (BMI), elevated serum glucose concentration, raised insulin (both fasting and OGTT), and increased hemoglobin A1c (HbA1c) levels. Higher homeostasis model assessment of insulin resistance (HOMA-IR) and decreased β-cell compensation (i.e., oral disposition index (DI

Acupuncture combined with western medication in treatment of type 2 diabetes mellitus with angina pectoris of coronary heart disease: a randomized controlled study / 中国针灸

OBJECTIVE@#To compare the therapeutic effect on type 2 diabetes mellitus (T2DM) complicated with angina pectoris of coronary heart disease between the combined therapy of acupuncture and western medication and the simple administration of western medication.@*METHODS@#A total of 134 patients with T2DM and angina pectoris of coronary heart disease were randomly divided into two groups, i.e. an acupuncture plus medication group (67 cases, 3 cases dropped off) and a medication group (67 cases, 4 cases dropped off). The routine western medication was used according to symptoms in the patients of both groups. In the acupuncture plus medication group, on the base of medication, acupuncture was applied to Jianshi (PC 5), Quchi (LI 11), Neiguan (PC 6), etc. The needles were retained for 20 min in each treatment and 3 treatments of acupuncture were required weekly. The treatment was given consecutively for 8 weeks in the two groups. Separately, before and after treatment, the symptom scores of TCM were observed and the indexes were detected, including glycolipid metabolism [fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), glucosylated hemoglobin (HbA1c), triacylglycerol (TG) and total cholesterol (TC)], islet β cell function [homeostasis model assessment-β (HOMA-β), homeostasis model assessment-IR (HOMA-IR), fasting insulin (FINS) and insulin sensitivity index (ISI)], cardiac function indexes [cardiac output (CO), early diastolic peak velocity/late diastolic peak velocity (E/A), left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF)], as well as electrocardiogram QT dispersion (QTd). Besides, the clinical therapeutic effects were compared between the two groups.@*RESULTS@#After treatment, the TCM symptom scores and the values of FPG, 2hPG, HbA1c, TG, TC, HOMA-IR, FINS, E/A and LVEDD as well as QTd were all lower than those before treatment in the two groups (@*CONCLUSION@#The combined therapy of acupuncture and medication is effective in treatment of T2DM complicated with angina pectoris of coronary heart disease. Such therapy effectively improves glucolipid metabolism, islet β cell function, cardiac function and myocardial blood supply. Its curative effect is better than the simple administration of western medicine.

Study on the correlation between serum vitamin D level, parathyroid hormone and type 2 diabetes mellitus in Inner Mongolia / 中华临床营养杂志

Objective:To evaluate the correlation of serum vitamin D (VitD) and parathyroid hormone (PTH) with insulin resistance and islet β-cell function in patients with type 2 diabetes mellitus (T2DM), and to analyze the role of serum VitD and PTH in the progression of T2DM.Methods:A total of 376 T2DM patients hospitalized in endocrinology department from January 2018 to January 2021 were selected. The baseline data were collected and the biochemical indexes were determined. Patients were divided into 3 groups according to serum VitD level, including 220 cases in deficiency group [25-(OH)D ≤ 20 μg/L], 107 cases in insufficiency group [25-(OH)D>20 and ≤ 30 μg/L] and 49 cases in sufficiency group [25-(OH)D > 30 μg/L]. Meanwhile, 31 of the patients were classified into PTH decreased group (PTH < 25.16 ng/L), 137 into normal PTH group (PTH ≥ 25.16 and < 38.35 ng/L) and 208 into PTH elevated group ( PTH ≥ 38.35 ng/L). According to body mass index (BMI), patients were divided into normal weight group (18.5 kg/m 2 ≤ BMI ≤ 23.9 kg/m 2), overweight group (BMI ≥24 and ≤ 27.9 kg/m 2) and obese group (BMI ≥ 28 kg/m 2). Results:Among the three groups defined by serum VitD level, comparisons of glucose metabolism and calcium and phosphorus metabolism indicators showed no significant differences in BMI, fasting insulin (FINS), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance index (HOMA-IR), serum calcium and phosphorus (all P > 0.05). The levels of glycated hemoglobin (HbA1c) and PTH in vitamin D deficiency group and sufficiency group were significantly lower compared with vitamin D deficiency group (both P < 0.05). Among the three groups defined by PTH level, there were no significant differences in BMI, FINS, FPG, HbAlc, HOMA-IR, and serum calcium (all P > 0.05). Serum phosphorus in the PTH elevated group was significantly lower compared with PTH decreased and normal PTH group ( P = 0.000), and VitD in the PTH elevated group was significantly lower compared with PTH decreased group ( P = 0.002). There were significant differences in age and blood phosphorus among the three groups defined by BMI level (all P<0.05). According to the analysis of clinical indexes of different nationalities, the level of VitD in Mongolians was significantly higher than that in Han nationality patients ( P <0.034). Spearman correlation analysis showed that VitD was negatively correlated with PTH and HOMA-IR and positively correlated with serum calcium. PTH was negatively correlated with serum calcium and phosphorus, and positively correlated with HOMA-IR. There was a significant negative correlation between normal PTH and VitD. Multiple linear regression analysis showed that HOMA-IR and homeostasis model assessment of β-cell function (HOMA-β) were protective factors, and FPG and FINS were risk factors for HOMA-IR and HOMA- β. Conclusion:There is a negative correlation between VitD and insulin resistance, and a positive correlation between PTH and insulin resistance, suggesting that VitD and PTH are possibly two impacting factors for T2DM pathogenesis.

The application of organoid models in diabetes research / 中华内分泌代谢杂志

Organoids are complex tiny organ-like model systems formed by three-dimensional culture in vitro, based on the self-renew and self-organization of stem cells. This article reviewed the recent progress in organoids construction from tissues involved in the regulation of glucose homeostasis and chronic diabetic microvascular complications, and their applications in diabetes mellitus. Organoid technology is expected to further promote the progress of diabetes research in disease modeling, personalized medicine, and regenerative medicine.

Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet β Cells / 基因组蛋白质组与生物信息学报·英文版

Type 2 diabetes (T2D) is characterized by the malfunction of pancreatic β cells. Susceptibility and pathogenesis of T2D can be affected by multiple factors, including sex differences. However, the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq), we demonstrate the presence of sexually dimorphic transcriptomes in mouse β cells. Using a high-fat diet-induced T2D mouse model, we identified sex-dependent T2D altered genes, suggesting sex-based differences in the pathological mechanisms of T2D. Furthermore, based on islet transplantation experiments, we found that compared to mice with sex-matched islet transplants, sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway of β cells. Moreover, the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance. These data suggest sexual dimorphism in T2D pathogenicity, indicating that sex should be considered when treating T2D. We hope that our findings could provide new insights for the development of precision medicine in T2D.