In order to study the expression change of insulin-like growth factor-1 (IGF-1) and its receptor genes in different generations of tendon cell in culture, Dig-labeled synthesized oligonucleotide probes were used to detect the mRNA expression in primary, 6th and 13th generation of tendon cell. The results showed that IGF-1 receptor mRNA was expressed in all of the 3 above generation tendon cells. IGF-1 mRNA was expressed only in primary and 6th generation cells. Tendon cell of 13th generation did not express IGF-1 mRNA. It might suggest that the absence of IGF-1 mRNA expression be one of the causes which led to the decrease of reproductive ability of 13th generation tendon cell.
OBJECTIVE: To investigate the effect of combined treatment of recombinant human growth hormone (rhGH) and insulin-like growth factor-1 (IGF-1) on wound healing and protein catabolism in burned rats. METHODS: Forty Wistar rats with deep II degree scald injury were divided randomly into four groups and received rhGH (0.1 U/kg.d), rhGH (0.1 U/kg.d) plus IGF-1 (2.0 mg/kg.d), IGF-1 (2.0 mg/kg.d) and Ringer’s solution (2 ml/kg.d, as control group) respectively. The wound healing time and protein catabolism levels of every groups were compared after 2 weeks. RESULTS: Total body weight began to increase after 2 weeks in rhGH group and rhGH plus IGF-1 group, but in control group, it was occurred after 4-5 weeks. The body weight of rhGH plus IGF-1 group was 1.65 times than that of rhGH group. The wound healing time in rhGH plus IGF-1 group (17.1 +/- 4.4) days was significantly lower than that of rhGH (20.5 +/- 4.8) days and control group (29.7 +/- 6.3) days. The protein level of rhGH plus IGF-1 group was significantly higher than that of control group and rhGH group. CONCLUSION: It suggests that rhGH plus IGF-1 with synergism is more effective in promoting wound healing and increasing the protein catabolism.
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.
Objective To observe the curative effect on non-obese type 2 diabetes and the effect on change of glucagon-like peptide-1 (GLP-1) of gastric bypass operation. Methods Thirty-two cases of gastric ulcer with non-obese type 2 diabetes were suffered gastric bypass operation. Plasma glucose concentrations, insulin and GLP-1 were measured respectively in fasting and postprandial conditions before operation and in week 1, 2, 3 and month 1, 3, 6 after gastric bypass operation, and the body mass index (BMI), homeostasis model assessment β cell function index (HBCI) and glycosylated hemoglobin (HbA1c， the index was detected only before operation and in month 3, 6 after operation) were also measured. The turnover of the diabetes condition in the 6th month after surgery was observed. Results Compared with the levels before operation, the fasting and postprandial plasma glucose levels were descending (P＜0.05), fasting and postprandial plasma insulin and GLP-1 levels were ascending (P＜0.05), HBCI was ascending and HbA1c was descending significantly after operation respectively (P＜0.05), while BMI changed un-significantly after operation (Pgt;0.05). The diabetes control rate was 78.1%(25/32) overall six months after operation. Level of GLP-1 was negatively correlated with level of plasma glucose (P＜0.05) and positively correlated with level of insulin (P＜0.05). Conclusions Gastric bypass operation can markedly reduce plasma glucose level on the type 2 diabetes patients with non-obese, and the hypoglycemic effect may be contributed by more GLP-1 secretion that caused more insulin secretion, which doesn’t depend on the loss of weight.
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.
Objective To explore the ability of insulin-like growth factor-Ⅰ (IGF-Ⅰ) and hyaluracan acid in prompting chondrogenesis of engineering cartilage tissue.Methods Human articular chondrocytes were isolatedand cultured in DMEM plus 10% fetal bovine serum. They were divided into three groups：hyaluracan acid+chondrocytes + IGF-Ⅰ group(IGF-Ⅰ group), hyaluracan acid+chondrocytes group(cell group), hyaluracan acid group(control group). The ability of chondrogenesis was investigated by HE and toluidine blue staining, human collagen Ⅱ immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR).Results Both cell group and IGF-Ⅰ group could develop into cartilage tissue in the sixth week while control group could not. The number of cartilage lacuna in IGF-Ⅰ group were more than that in cell group. Human collagen Ⅱ immunohistochemistry showed that there were ber positive cell in IGF-Ⅰ group than in cell group, collagen Ⅱ mRNA expression was more higher and collagen Ⅰ mRNA expression was lower in IGF-Ⅰ group than in cell group. Conclusion Insulin growth factorⅠ can prompt chondrogenesis of engineering cartilage tissue and ameliorate the quality of engineering cartilage tissue in vitro.
Objective To investigate the insulin receptor expression and binding characteristics of H22 rat hepatic cancer cell membrane with 125Iinsulin and the possibility of using insulin as a carrier for the receptor mediated targeted therapy. MethodsInsulin was radiolabelled using ChT method, isolated and purified by polyacrylamide gel electrophoresis, the labelled 125Iinsulin was measured by specific activity selfreplacement and over dose receptor combination experiment. The rat H22 hepatocarcinoma cells, normal rat hepatic cells were made, continuing the value Kd and Bmax of 125Iinsulin binding with insulin receptor on rat H22 hepatocarcinoma and normal hepatic cells membrane were evaluated in vitro, the competed binding curve was pictured. The binding Kd and Bmax value of 125Iinsulin receptor were evaluated with t test and receptor binding curve was tested with Scatchard method. ResultsThe Bmax value of rat H22 hepatocarcinoma cell receptor ［(5.6±1.1) pmol/106 cell］ was higher than that of normal hepatic cell ［(3.2±0.8) pmol/106 cell］ significantly (P＜0.05). The Kd value of H22 cell ［high and lowaffinity vs (1.8±0.6) nmol/L and (32.0±10.7) nmol/L］ and normal hepatic cell ［high and low affinity vs (2.1±0.9) nmol/L and (37.0±12.3) nmol/L］ were not significant respectively. In this experiment, it was specific when 125Iinsulin combined with receptor on H22 hepatocarcinoma cell and rat normal hepatic cell membrane. Conclusion This experiment showed that the receptor expresses much more significantly on H22 hepatocarcinoma cell membrane than that on normal rat hepatic cell membrane, 125Iinsulin combining with receptor on H22 hepatocarcinoma cell and rat hepatic cell membrane is highly specific. We may use insulin as an anticancer carrier to mediate insulin combined with receptor on hepatocarcinoma cell membrane in the target treatment of hepatic cancer.
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.
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 investigate the effects of intermittent irrigation of insulin solution combined with continuous drainage of vacuum sealing drainage (VSD) in chronic diabetic lower limb ulcers. MethodsBetween January 2012 and December 2014, 45 patients with diabetic lower limb ulcer were treated with VSD (group A, n=15), with VSD combining irrigation of normal saline (group B, n=15), and with VSD combining irrigation of insulin solution (group C, n=15) after debridement. There was no significant difference in gender, age, course of ulcers, area and depth of wound, glycosylated hemoglobin, and Wagner grade among 3 groups (P>0.05), and the data were comparable. The levels of fasting blood glucose, 2-hour postprandial blood glucose, and random blood glucose were determined everyday during treatment. The contents of insulin growth factor 1 (IGF-1), tumor growth factor α (TNF-α), and nitric oxide (NO) in necrotic tissue after drainage were determined. The coverage rate and thickness of granulation tissue and clearance rate of bacteria in wound were calculated, the granulation tissue in the center of the wound was harvested for pathological observation with HE staining after 6 days of treatment. The second stage operation was performed according to the condition of wounds, and the time to the second stage operation and the method of the second stage operation were recorded and the survival rate of grafted skin or flap was calculated. ResultsThe pathological staining showed that there were a few new microvessels and fibroblasts in group A after treatment;more new microvessels and fibroblasts were observed in group B;and many new microvessels and fibroblasts were found in group C. There was no significant difference in levels of fasting blood glucose, 2-hour postprandial blood glucose, and random blood glucose among 3 groups during treatment (P>0.05). The coverage rate and thickness of granulation tissue and clearance rate of bacteria in group C were significantly higher than those in groups A and B after treatment (P<0.05). The contents of IGF-1 and NO were significantly increased and TNF-α was significantly decreased in group C when compared with those in group A (P<0.05). Compared with group B, IGF-1 and NO contents were significantly increased at 3-6 days and at 2-6 days respectively, and TNF-α content was significantly decreased at 3-6 days in group C (P<0.05). The method of the second stage operation showed no significant difference among 3 groups (χ2=2.920, P=0.230), but the time to the second stage operation in group C was significantly shorter than that in groups A and B (P<0.05), and the survival rate of grafted skin or flap in group C was significantly higher than that in groups A and B (P<0.05). ConclusionThe treatment of diabetic lower limb ulcers with intermittent irrigation of insulin solution combined with continuous drainage of VSD can reduce inflammatory reaction effectively, promote development of granulation tissue, improve recovery function of tissue, increase the rate and speed of wound healing obviously, but it has no effect on blood glucose levels.