Objective To summarize the relationship of diabetes and its complications with microRNA. Methods Domestic and international researches were collected by searching to summarize the role of microRNA in diabetes and its complications. Results MicroRNA could affect the secretion of insulin and interfer metabolism of gulcose in fat cells， muscle cells， and liver cells， which resulting in insulin resistance. At the same time， the microRNA also played an role in damage of vascular endothelial cells and myocardial cell in diabetes. Conclusion MicroRNA acts an important role in the process of diabetes and its complications.
ObjectiveTo investigate the relationship between insulin-like growth factor binding protein (IGFBP) gene with pancreatic cancer. MethodsThe relevant literatures at home and abroad in recent years were reviewed. From the pancreatic cancer related genes, IGFBP related tumors and the correlation between IGFBP and pancreatic cancer research and other aspects of the previous research results were summaried. ResultsMost of the studies suggested that IGFBP could inhibit the function of tumor cells through the IGF dependent pathway, but the deletion or mutation of IGFBP gene and its regulation mechanism are still unclear. ConclusionIGFBP is closely related to the tumor, but its specific effects and mechanism of pancreatic cancer has not been settled. In order to affect the degree of cell differentiation, regulation of tumor growth and metastasis probability through the change of endogenous IGFBP gene level, the further studie is needed.
ObjectiveTo systematically evaluate the changes in placental protein expressions in gestational diabetes mellitus (GDM) and their correlations with maternal insulin resistance (IR). Methods PubMed, Cochrane Library, Scopus, Web of Science, Embase, China National Knowledge Infrastructure, VIP database, Wanfang Database and CBMdisc were searched for case-control studies published from January 2009 to November 2021, which reported the placental protein expressions in GDM and their correlations with IR. Two researchers independently reviewed the literature, extracted data and evaluated the literature quality. RevMan 5.4 software was used for meta-analysis, and descriptive analysis was performed on data that cannot be combined. ResultsA total of 19 studies were included, comprising 2 012 patients. The results of meta-analysis showed that: the expression level of retinol binding protein 4 (RBP4) [standard mean difference=2.11, 95% confidence interval (CI) (1.64, 2.58), P<0.000 01] and the positive rate of protein tyrosine phosphatase-1B (PTP1B) [relative risk (RR)=1.56, 95%CI (1.29, 1.88), P<0.000 01] were up-regulated, and the positive rate of insulin receptor substrate 1 (IRS-1) [RR=0.69, 95%CI (0.60, 0.78), P<0.000 01] was down-regulated. The protein expression levels of RBP4 (P<0.000 01) and PTP1B (P<0.000 01) were positively correlated with homeostasis model assessment of insulin resistance (HOMA-IR), while the protein expression levels of IRS-1 (P<0.000 01) and APN (P=0.002) were negatively correlated with HOMA-IR, and glucose transporter 4 (GLUT 4) was not correlated with HOMA-IR (P=0.79). Descriptive analysis found that the expression levels or positive rates of adipocytokines (leptin, resistin), oxidative stress markers (xanthione oxidase, malondialdehyde, 8-isoprostaglandin),inflammatory factors (tumor necrosis factor α, Toll-like receptor 4, Galectin-3, Galectin-2, migration inhibitory factor),fetuin-A, forkhead box transcription factor 1, forkhead box transcription factor 3a and estrogen receptor α in GDM placenta were up-regulated and all were positively correlated with HOMA-IR. The expression levels or positive rates of insulin signaling pathway proteins [phosphoinositide 3-kinase (PI3K), protein kinases B (AKT), phospho-protein kinases B (p-AKT), GLUT 4] were down-regulated, PI3K and AKT were negatively correlatedwith HOMA-IR, while p-Akt had no correlation with HOMA-IR. ConclusionsThe dysregulation of placental protein expressions may mediate maternal IR exacerbation, thus promote the occurrence and development of GDM and other pregnancy complications. The causal relationship and regulatory mechanism are still unclear, which need to be further studied.
【Abstract】 Objective To explore the new therapy for pulmonary fibrosis by observing the effects of insulin-like growth factor 1 ( IGF-1) treated mesenchymal stemcells ( MSCs) in rats with bleomycin-induced pulmonary fibrosis. Methods Bone marrowmesenchymal stemcells ( BMSCs) were harvested from6-week old male SD rats and cultured in vitro for the experiment. 48 SD rats were randomly divided into 4 groups, ie.a negative control group ( N) , a positive control group/bleomycin group ( B) , a MSCs grafting group ( M) ,and an IGF-1 treated MSCs grafting group ( I) . The rats in group B, M and I were intratracheally injected with bleomycin ( 1 mL,5 mg/kg) to induce pulmonary fibrosis. Group N were given saline as control. Group M/ I were injected the suspension of the CM-Dil labled-MSCs ( with no treatment/pre-incubated with IGF-1 for 48 hours) ( 0. 5mL,2 ×106 ) via the tail vein 2 days after injected bleomycin, and group B were injected with saline ( 0. 5 mL) simultaneously. The rats were sacrificed at 7,14,28 days after modeling. The histological changes of lung tissue were studied by HE and Masson’s trichrome staining. Hydroxyproline level in lung tissue was measured by digestion method. Frozen sections were made to observe the distribution of BMSCs in lung tissue, and the mRNA expression of hepatocyte growth factor ( HGF) was assayed by RTPCR.Results It was found that the red fluorescence of BMSCs existed in group M and I under the microscope and the integrated of optical density ( IOD) of group I was higher than that of group M at any time point. But the fluorescence was attenuated both in group M and group I until day 28. In the earlier period, the alveolitis in group B was more severe than that in the two cells-grafting groups in which group I was obviously milder. But there was no significant difference among group I, M and group N on day 28.Pulmonary fibrosis in group B, Mand I was significantly more severe than that in group N on day 14, but itwas milder in group M and I than that in group B on day 28. Otherwise, no difference existed between the two cells-grafting groups all the time. The content of hydroxyproline in group B was significantly higher than that in the other three groups all through the experiment, while there was on significant difference betweengroup I and group N fromthe beginning to the end. The value of group M was higher than those of group I and group N in the earlier period but decreased to the level of negative control group on day 28. Content of HGF mRNA in group Nand group I was maintained at a low level during the whole experiment process. The expression of HGF mRNA in group I was comparable to group M on day 7 and exceeded on day 14, the difference of which was more remarkable on day 28. Conclusions IGF-1 can enhance the migratory capacity of MSCs which may be a more effective treatment of lung disease. The mechanismmight be relatedto the increasing expression of HGF in MSCs.
ObjectiveTo study the characteristics of the human umbilical cord perivascular cells (HUCPVC) isolated from human first trimester umbilical cord perivascular layer tissues and the differentiation into islet-like cell clusters in vitro. MethodsThe HUCPVC derived from human first trimester umbilical cord which was donated by the volunteers were isolated and subcultured. The surface markers such as stage-specific embryonic antigen 1 (SSEA-1), SSEA-3, SSEA-4, OCT-4, TRA-1-60, and TRA-1-81 were detected by immunohistochemical method. The first trimester HUCPVC were induced to embryoid bodies (EB)-like cell aggregations and islet-like cell clusters in vitro through a simple stepwise culture protocol (5 steps). The expressions of specific markers[α-fetoprotein (AFP), Nestin, and smooth muscle actin (SMA)] were measured by immunohistochemical method; and the ability of glucose-stimulated insulin secretion was analyzed. ResultsThe first trimester HUCPVC were successfully isolated and could be passaged steadily more than 10 generations, which expressed SSEA-3, SSEA-4, OCT-4, TRA-1-61, and TRA-1-81. The first trimester HUCPVC were successfully induced into EB-like cell aggregations and islet-like cell clusters. The EB-like cell aggregations could express markers of three germ lineages:AFP, Nestin, and SMA. The islet-like cell clusters could release insulin significantly in response to elevated concentrations of glucose in vitro (t=7.444, P=0.002). The insulin contents were (23.2±5.3) mU/L and (7.0±0.5) mU/L in high and low glucose media, respectively. ConclusionThe first trimester HUCPVC has the ability to differentiate into islet-like cell clusters which can secret insulin in vitro.
ObjectiveTo study the effect of exogenous insulin on inducing angiogenesis and the expression of vascular endothelial growth factor (VEGF) of hindlimb ischemia of rats with diabetic. MethodsThe hindlimb ischemic model of diabetic rat was established by the ligation of femoral blood vessels of hindlimb in twenty healthy male SD rats and which were divided into model group (n=10) and treatment group (n=10). Another 10 normal rats were selected as control group. Then the expression of VEGF protein and capillary density of muscle tissues of rat hindlimb were detected by Western blot analysis and alkaline phosphatase (APK) stain method, respectively. ResultsThe differences of body weight and blood glucose level of rats before operation and on day 7 after operation were not significant in the control group (Pgt;0.05). The body weight of rat was significantly lower on day 7 after operation than that before operation in the model group (Plt;0.05), while the difference of blood glucose level of rats was not significant in the model group (Pgt;0.05). The body weight and blood glucose level of rat significantly decreased in the treatment group on day 7 after subcutaneous injection of insulin as compared with the level before operation (Plt;0.05). Compared with the control group, the body weight decreased and blood glucose level increased in the model group and treatment group, and the difference was significant (Plt;0.05, Plt;0.01). The body weight of rat in the treatment group was not different from that in the model group (Pgt;0.05), but the blood glucose level of rat on day 7 after operation in the treatment group was significantly lower than that in the model group (Plt;0.05). The relative expression of VEGF protein of muscle tissues of ischemic hindlimbs in the treatment group (155.06±10.26) was significantly higher than that in the model group (94.30±11.23), Plt;0.05, while no expression was found in the control group. The capillary density of muscle tissues of right hindlimb in the control group was significantly higher than that in the model group or treatment group (Plt;0.05), and furthermore, which was higher in the treatment group than that in the model group (Plt;0.05). The difference of capillary density of muscle tissues of left hindlimb was not different among three groups (Pgt;0.05). The capillary density of muscle tissues of right hindlimb was not different from that of left hindlimb in the control group (Pgt;0.05) and which was significantly lower than that of left hindlimb in the model group or treatment group (Plt;0.05). ConclusionInsulin may increase the expression of VEGF protein in ischemic muscle tissue of diabetic rats and protect the ischemic muscle.
Objective To establish a stable colorectal cancer model in liver specific insulin-like growth factor (IGF)-1 deficient (LID) mice and examine the potential relationship between IGF-1 level and risk of mice constitutional colorectal cancer. Methods ①Establishment of a colorectal cancer model: The LID mice, in which IGF-1 level in circulation was 25% of BALB/c mice. Induction of colorectal cancer was achieved by using the 1,1 Dimethylhydrazine (DMH) with hypodermic injection at transverse part. ②Eighty fresh samples of cancer tissues and adjacent tissues were obtained from LID mice (experimental group) and BALB/c mice (control group). The expression of IGF-1 was studied by immunohistochemical assay (SP method). Results ①Weight loss occurred in both experimental group and control group after injection. Compared with the body weight before injection on 18 weeks and 24 weeks in each group, there were significant differences after injection at the same phase in each group (P＜0.05). ②The results of IGF-1 expression in cancer tissues and adjacent tissues: IGF-1 got a diffuse distribution in cancer cell cytoplasm. The positive expressions of IGF-1 in the cancer tissues and their adjacent cancer tissues were 6/7, 2/7 and 13/16, 7/16 respectively in experimental group and control group. There were significant differences between the cancer tissues and adjacent tissues inside both groups (P＜0.05). There were no significant differences inside both of cancer tissues and adjacent tissues respectively between experimental group and control group (Pgt;0.05). Conclusion In the established colorectal cancer model by DMH, IGF-1 plays an important role in the development and progression of colorectal cancer.
Objective To investigate the ability of repairing bone defect with the compound of recombinant human insulinlike growth factor 1 (rhIGF-1), coralline hydroxyapatite(CHA) and autogeneous red bone marrow(ARBM), and to study the feasibility of the compounds being used as bone substitute materials. Methods Bilateral radius bone defects(11 mm in length) were created in 54 Chinese rabbits,which were randomly divided into 3 groups, and two different materials were randomly transplanted into the bilateral defects:in group 1, with material A(rhIGF-1/CHA/ARBM) and material B(CHA/ARBM); in group 2, with material C(rhIGF-1/CHA) and material D(CHA); in group 3, with E(autograft) and F(no implant) as controls. At 2, 4, 8 and 12 weeks, the effects were assessed by X-ray andimage analysis, biomechanics(at 12 weeks), as well as histological observation. Results X-ray and image analysis showed that material A of group 1was significantly superior to any other materials(P＜0.01). Antibending biomechanic detection showed that material A and Ewas significantly superior to the other materials(Plt;0.01), but no significant difference was found between A and E in the 12th week(Pgt;0.05). And by histological observation, in analogical bone morphological progress, materials C and D obviously inferior to materials A, B and E, but there was no significant difference between materials C and D. F had no evidence of new bone rebridging. Conclusion The recombinant compound CHA/ARBM(rhIGF-1),which posseses the potential ability of osteogenesis,osteoconduction and osteoinduction for bone defect repairing,can serve as a new type of autogenous bone substitute material.
ObjectiveTo investigate the effects and mechanisms of differentiation of bone marrow mesenchymal stem cells (BMSCs) into insulin producing cells (IPCs) induced by injured pancreatic tissue extract of rat. MethodsEighty 6-week-old Sprague Dawley rats were selected. Forty rats underwent removal of 60% pancreas and the injured pancreas tissue was obtained after 48 hours to prepare the injured pancreatic tissue extract; and normal pancreatic tissue extract was prepared from the other 40 rats. The BMSCs were isolated from the tibia and femur of 4-week-old Sprague Dawley rats. BMSCs at passage 3 were co-cultured with rat injured pancreatic tissue extract as experimental group, with rat normal pancreatic tissue extract as normal control group, and with cell culture medium as blank control group for 14 days. The expressions of pancreas development related genes and proteins were detected, and cell morphological changes were observed. Then the C peptide positive cell rate was detected by flow cytometry analysis and insulin secretion levels were detected by glucose stimulation experiment at 14 days. ResultsInjured pancreatic tissue extract can induced BMSCs differentiating into IPCs. The pancreatic development related genes of pancreatic duodenal homeobox 1 (PDX-1), islet 1, Nkx6.1, glucose transporter type 2, proprotein convertase 2, neurogenin 3, and somatostatin were expressed sequentially in the differentiation process of experimental group; mature pancreatic proteins of PDX-1, insulin, C peptide, Nkx6.1 also were expressed. But there was no morphological changes and expression of pancreatic development related genes and proteins in normal control and blank control groups. The C peptide positive cell rate of experimental group (13.8%±1.8%) were significantly higher than those of normal control and blank control groups (1.6%±0.4%) (P<0.05). The insulin secretion of experimental group was significantly higher than that of normal control and blank control groups (P<0.05), but it was 1/40 and 1/47 of natural islet cells (P<0.05). ConclusionAfter pancreatic injury, injured pancreas would secrete transcription proteins related to development, differentiation, and repair of pancreas, which can promote the differentiation of BMSCs into IPCs.
Objective To investigate the clinical significance of insulin resistance ( IR) in chronic obstructive pulmonary disease ( COPD) .Methods Patients with stable COPD were recruited while healthy volunteers were enrolled as control. The diagnosis and severity assessment were made according to chronic obstructive pulmonary disease diagnosis and treatment guideline ( revised edition 2007) . Fasting serum levels of glucose ( FBG) , insulin ( FIN) , blood lipids, fibrinogen, C-reactive protein ( CRP) , tumor necrosis factor ( TNF-α) , and interleukin-6 ( IL-6) were measured. The degree of IR was calculated by IAI( IAI =1/FBG ×FIN) . The relationship of IR with COPD severity and above parameters was analyzed. Results A total of 121 subjects with COPD were enrolled in which 22 cases of mild COPD, 28 cases of moderate COPD,34 cases of severe COPD, and 37 cases of extremely severe COPD. The levels of FBG and FIN were significantly higher in the COPD group than those in the normal control group ( P lt;0. 05) . ISI in the COPD patients was higher than that in the controls ( - 3. 88 ±0. 54 vs. - 3. 40 ±0. 28, P lt;0. 05) . The levels of CRP, fibrinogen, TNF-α, and IL-6 were significantly higher in the COPD group than those in the control group ( P lt;0. 05) . The levels of CRP, TNF-αand IL-6 increased progressively with the severity of COPD. There was a negative correlation between ISI and the severity of COPD ( r = - 0. 512, P lt; 0. 01) , positive correlations of CRP, fibrinogen, TNF-αand IL-6 levels with COPD severity, respectively( r=0. 710, 0. 600,0. 708,0. 707, all P lt;0. 01) , and negative correlations of ISI with the levels of CRP, fibrinogen, TNF-α and IL-6 ( r = - 0. 384, - 0. 240, - 0. 298, - 0. 396, all P lt; 0. 01) , respectively. Conclusion There is an increase in fasting serum insulin and insulin resistance in patients with COPD compared with healthy subjects, which deteriorates with severity of COPD.