Liver cirrhosis (LC) and insulin resistance (IR) are closely correlated, clinically presenting hyperglycemia, hyperinsulinism, hyperlipidemia and high cytokines levels, however, the underlying mechanism is not completely clear. Recent reports show that insulin receptor substrate-1 (IRS-1) is associated with IR in LC. IRS-1 plays a pivotal role on insulin signal transduction; it changes insulin signaling by up-or down-regulating of protein presentation, post-translational modification and subcellular localization of proteins, particularly in phosphorylation/dephosphorylation of post-translational modification. Furthermore, LC with different etiology may have different mechanism of IRS-1 effect on IR.
Humans ; Insulin ; metabolism ; Insulin Receptor Substrate Proteins ; metabolism ; physiology ; Insulin Resistance ; Liver Cirrhosis ; metabolism

OBJECTIVETo study the expression of insulin receptor substrate-1(IRS-1) and insulin receptor substrate-2 (IRS-2) in pancreas of rats with intrauterine growth retardation (IUGR).

METHODSAn IUGR rat model was prepared by protein malnutrition during pregnancy. The pancreas samples of the IUGR pups were obtained at birth, and 3 weeks and 8 weeks of age. The expression of IRS-1 and IRS-2 mRNA were ascertained by RT-PCR. Western blot was used to measure the protein expression of IRS-1 and IRS-2. The rat pups born from the mother rats who received normal diet during pregnancy severed as the control group.

RESULTSThe expression levels of IRS-2 mRNA and protein in pancreas of the IUGR group were significantly lower than those in the control group at all three time points (P<0.05). There were no significant differences in the expression levels of IRS-1 mRNA and protein in pancreas between the IUGR and the control groups.

CONCLUSIONSThe IRS-2 expression levels in pancreas in IUGR rats decrease significantly at birth, and 3 weeks and 8 weeks of age. This might be one of the molecular mechanisms for the development of metabolic syndrome in later life in IUGR individuals.

Animals ; Fetal Growth Retardation ; metabolism ; Insulin Receptor Substrate Proteins ; RNA, Messenger ; Rats ; Receptor, Insulin

No abstract available.
Animals ; Carbohydrate Metabolism* ; Hindlimb Suspension* ; Hindlimb* ; Insulin* ; Muscle, Skeletal* ; Rats* ; Receptor, Insulin*

OBJECTIVETo study the relationship between insulin resistance and methylation of insulin receptor (INSR) gene in the endometrium of women with polycystic ovary syndrome (PCOS).

METHODSBased on the HOMA index, 35 patients with PCOS were divided into insulin resistant group (IR group, n=18) and non-resistant group (NIR group, n=18). The patients age, serum estriol, testosterone, FSH and LH, fasting insulin and fasting blood glucose were compared between the two groups. The endometrial samples were obtained from the patients to examine DNA methylation status of INSR gene in the endometrial cells using methylation-specific PCR.

RESULTSThe BMI, WHR, fasting glucose, fasting insulin, and HOMA index differed significantly between the two groups (P<0.05). PCR analysis showed partial methylation in the promoter region of INSR gene in 13 samples in IR group and 11 samples in NIR group, without detection of full methylation of the INSR gene in either group. The methylation status showed no significant difference between the two groups (P=0.328).

CONCLUSIONPartial methylation of the INSR gene occurs in the endometria of PCOS patients, but this study does not provide a strong evidence supporting the relationship between insulin resistance and INSR gene methylation in women with PCOS.

Adult ; DNA Methylation ; Endometrium ; metabolism ; Female ; Humans ; Insulin Resistance ; Polycystic Ovary Syndrome ; genetics ; metabolism ; Receptor, Insulin ; genetics ; metabolism

OBJECTIVETo investigate the effect of Bushen Tongmai recipe (BSTMR) on the tyrosine phosphorylation of insulin receptor (InsR) and insulin receptor substrate-1 (IRS-1) after insulin stimulation in muscle and fat tissues of insulin resistant (IR) rats induced by high-fat forage.

METHODSMale Wistar rats were randomly divided into normal group (normal forage), model group (high fat forage, in which 61% calories were supplied by fat) and treated group (same forage as model group and treated with BSTMR). All animals were fed for 8 weeks, fasting blood glucose (FBG), blood glucose (BG) levels 1- and 2-hrs after glucose loading were determined routinely, serum fasting insulin (Ins) was determined with radioimmunoassay (RIA) and tyrosine phosphorylation level of InsR and IRS-1 in fatty and muscular tissues was measured by immunoprecipitation and Western blot.

RESULTSCompared with the model group, FBG in the treated group changed insignificantly, but level of Fins decreased markedly (P < 0.01), so the insulin sensitivity index was significantly elevated in the treated group (P < 0.01), levels of BG 1- and 2-hrs after glucose loading in the treated group were greatly improved in comparison with those in the model group (P < 0.05 and P < 0.01 respectively). Meanwhile, the density of electrophoresis bands of tyrosine phosphorylated InsR and IRS-1 proteins in muscular and fatty tissues in the treated group increased obviously.

CONCLUSIONBSTMR could attenuate the insulin resistance in rats, its pharmaceutical mechanisms might be closely related with the elevation of the tyrosine phosphorylation levels of InsR and IRS-1 in muscular and fatty tissues after insulin stimulation, and improvement of insulin signal transduction in target tissues.

Animals ; Blood Glucose ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Insulin ; metabolism ; Insulin Receptor Substrate Proteins ; Insulin Resistance ; physiology ; Male ; Phosphoproteins ; drug effects ; Phosphorylation ; Random Allocation ; Rats ; Rats, Wistar ; Receptor, Insulin ; metabolism ; Signal Transduction ; drug effects ; Tyrosine ; metabolism

As a hormone with a number of biological effects, insulin not only displays the function of classic metabolic regulation, but also can regulate cell proliferation and differentiation, and ensure growth and development of embryos and young individuals. In vitro insulin can stimulate cell proliferation and differentiation. Insulin is also an important growth regulator in vivo, which has been proved in more and more studies. The role of insulin at the cellular level is triggered by the binding of insulin to its receptor located in the cell surface. However, insulin at the higher concentration can also been triggered by insulin-like growth factor-1 (IGF-1) receptor. Its role varies in different cell lines. Insulin receptor and insulin-like growth factor receptor-1 are widely expressed in human MDS and AML cell membranes. Recently, many studies related to the relationship between hyperinsulinemia and cancer have been reported. In this review the role and its possible mechanism in promoting human leukemia cell proliferation and inhibiting human leukemia cell proliferation are summarized. Furthermore, the potential application prospect of insulin analogues also will be described.
Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Humans ; Insulin ; pharmacology ; Leukemia ; metabolism ; pathology ; Receptor, IGF Type 1 ; metabolism ; Receptor, Insulin ; metabolism

This study was aimed to explore the effects of insulin on expression of insulin receptor (IR) and insulin-like growth factor-I receptor (IGF-IR) in Reh cells and promoting effect on proliferation of Reh cells. The proliferation of Reh cells were evaluated by CCK-8 assay. The expression levels of IR and IGF-IR mRNA in Reh cells at different times were detected by real-time quantitative polymerase chain reaction. The results showed that insulin promoted the proliferation of Reh cells in dose- and time-dependent manners. Compared with the control group, insulin promoted the proliferation of Reh cells obviously (P < 0.05). When Reh cells were treated with insulin 10(-9) mol/L for 24, 48 and 72 h, the relative quantity of IR expression (2(-ΔCt1)/2(-ΔCt2)) was 2.2520 ± 0.7431, 1.9956 ± 0.9692 and 3.9766 ± 1.3189, respectively, the relative quantity of IGF-IR expression was 1.0803 ± 0.2238, 1.6026 ± 0.6158 and 3.1013 ± 0.1008, respectively, compared with the control group. The expression levels of IR and IGF-IR mRNA in Reh cells treated with insulin were obviously increased compared with the control group. It is concluded that insulin promotes the proliferation of Reh cells. The high expression levels of IR and IGF-IR may closely related with the growth of leukemia cells.
Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Insulin ; pharmacology ; Leukemia, Lymphoid ; metabolism ; pathology ; Receptor, IGF Type 1 ; metabolism ; Receptor, Insulin ; metabolism

Many reports have documented a role of insulin and insulin-like growth factor 1 (IGF-1) as growth factors in many cancers. The sequence and structure of insulin receptor (IR) and IGF receptor (IGF-1R) are highly similar. Both receptors are overexpressed in leukemia cells.Studies indicate that insulin can enhance the signal of the phosphoinositide 3-kinase/Akt pathways by activating IR or IGF-1R or hybrid IR/IGF-IR receptors, resulting in the proliferation of leukemia cells. High concentration of insulin may inhibit the growth of leukemia cells, the mechanism of which remains to be unclear. Inhibiting IR and IGF-IR can diminish the proliferation of leukemia cells. Therefore, the assumption of IR/IGF-1R as a potential therapeutic target in leukemia appears reasonable. This article summarizes the recent advancement associated with the signaling pathway of insulin effecting the proliferation of leukemia cells.
Cell Line, Tumor ; Cell Proliferation ; Humans ; Insulin ; Insulin-Like Growth Factor I ; metabolism ; Leukemia ; metabolism ; pathology ; Receptor, Insulin ; metabolism ; Signal Transduction

OBJECTIVETo investigate the mechanism of hepatocytic insulin signal transduction defects in severely scalded rats, so as to clarify the molecular basis of postburn insulin resistance.

METHODSWistar rats inflicted by 30% III degree scalding on the back were employed as the model. The rat hepatocytic insulin receptor was partially purified by wheat-germ agglutinin (WGA)-sepharose 4B affinity chromatography. The change of receptor tyrosine protein kinase (TPK) activity, the receptor beta-subunit autophosphorylation and the hepatocytic insulin receptor binding behavior of scalded rats during early stage of scalding were observed by means of insulin receptor binding test, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) autoradiography of phosphorylation of insulin receptor and phosphorylation of exogenous substrate.

RESULTSThere exhibited no evident changes of hepatocytic insulin receptor maximal binding capacity and affinity at 3 postburn days (PBDs) in scalded rats. The autophosphorylation capacity of the receptor beta-subunit decreased significantly. And the receptor TPK activity decreased obviously and its reaction to insulin stimulation decreased markedly.

CONCLUSIONThe defects of the insulin receptor signal transduction in hepatocyte leading to the post-receptor defects of insulin biological effects might be molecular mechanism of postburn insulin resistance.

Animals ; Burns ; metabolism ; pathology ; physiopathology ; Disease Models, Animal ; Hepatocytes ; metabolism ; Insulin ; physiology ; Insulin Resistance ; physiology ; Phosphorylation ; Rats ; Rats, Wistar ; Receptor, Insulin ; metabolism ; Signal Transduction ; physiology

Animals ; Colorectal Neoplasms ; blood ; etiology ; Humans ; Hyperinsulinism ; blood ; complications ; Insulin ; blood ; Insulin Resistance ; Insulin-Like Growth Factor Binding Proteins ; blood ; Insulin-Like Growth Factor I ; metabolism ; Metabolic Syndrome ; blood ; complications ; Receptor, IGF Type 1 ; blood ; Receptor, Insulin ; blood