No abstract available.
Humans* ; Insulin* ; Receptor, Insulin*

Childhood obesity is a global epidemic, which leads to the increasing number of studies on genetic locations associated with obesity-related traits. Polymorphisms of insulin (INS) gene have been shown to be associated with obesity-related phenotypes in Europeans; while insulin receptor (INSR) gene has been associated with energy regulation. Therefore, this study was conducted to investigate the association between the INS (rs689) and INSR (rs3745551) gene polymorphisms with childhood obesity risk in a Malay childhood population. Normal weight (538) and overweight or obese (557) children aged 6-12 years old were genotyped using semi-automated Sequenom iPLEX® Gold. Body mass index (BMI) was calculated from measured body weight and height. The rs689 (T/T: 0.006, A/T: 0.159 and A/A: 0.835) and rs3745551 (G/G: 0.054, A/G: 0.378 and A/A: 0.568) genotype distributions were consistent with Hardy Weinberg equilibrium. The T-minor allele frequency for rs689 was 8.6% and G-minor allele frequency for rs3745551 was 24.3%. Minor allele of INS gene polymorphisms significantly increased risk of obesity among Malay children (sex- and age-adjusted OR=1.580; 95%CI: 1.134-2.201). However, INSR gene polymorphisms were not significantly associated with childhood obesity. In conclusion, the polymorphisms of INS gene, rather than INSR gene, were associated with childhood obesity in the Malay population.
Pediatric Obesity ; Receptor, Insulin

No abstract available.
Empty Sella Syndrome ; Hypoglycemia ; Insulin ; Receptor, Insulin

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

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

PURPOSE: The insulin-like growth factor (IGF) system performs multiple functions in the regulation of breast cancer cell growth. The IGF system is comprised of a complex network of ligands, receptors and related signaling proteins. Two receptors are recognized, the insulin-like growth factor-I receptor (IGF-IR) and the insulin-like growth factor- II receptor (IGF-IIR), one of which, the IGF-IR, is a transmembrane heterodimer structurally similar to the insulin receptor. The activation of the IGF-IR results in the recruitment of adapter proteins, which adapter proteins used by the insulin-like growth factor-I (IGF-I) to transduce its signal to the insulin receptor substrate-1 (IRS-1). This study investigated the relationship between IGF-IR and IRS-1 by using an immunohistochemical staining technique. METHODS: IGF-IR and IRS-1 expression was detected by immunohistochemical staining using paraffin sections in 123 invasive breast carcinoma cases. The results were evaluated with the survival rate and the clinicopathological prognostic variables such as the patient's age, the clinical stage, the histological grade, the estrogen receptor (ER) and the progesterone receptor (PR). RESULTS: The results showed that IGF-IR and IRS-1 expression positively correlated with the ER and PR, and an inverse relationship was found between the IGF-IR and IRS-1 and histological grades. No association was observed between the IGR-IR and IRS-1 and the patent's age and clinical stage. In survival analysis, there was no definite association between the expressions of IGF-IR and IRS-1 and the disease free survival rate. CONCLUSION: IGF-IR and IRS-1 appear to play a role in the progression and differentiation of breast cancer in association with the ER and the PR.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Estrogens ; Insulin Receptor Substrate Proteins* ; Insulin* ; Ligands ; Paraffin ; Receptor, Insulin* ; Receptors, Progesterone ; Survival Rate

Mesenchymal tumors including hemangiopericytomas, hepatocellular tumors, adrenal carcinomas, and a variety of other large tumors have been reported to produce excessive amounts of insulin-like growth factor (IGF) type II precursor, which binds weakly to insulin receptors and strongly to IGF-I receptors, leading to insulin like actions. In addition to increased IGF-II production, IGF-II bioavailability is increased due to complex alterations in circulating binding proteins. The authors of this article diagnosed non-islet cell tumor hypoglycemia from an 81-year-old male patient suffering from repetitive fasting hypoglycemia while he has not received any treatment for pulmonary hemangiopericytoma diagnosed in the past. Moreover, this topic is getting reported as the authors have experienced a significant improvement of catamnesis by a treatment with glucocorticoid.
Aged, 80 and over ; Biological Availability ; Carrier Proteins ; Hemangiopericytoma ; Humans ; Hypoglycemia* ; Insulin ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Male ; Receptor, IGF Type 1 ; Receptor, Insulin

OBJECTIVETo investigate the expressions of adipic insulin receptor β(IR-β) and insulin receptor substrate-1 (IRS-1) after gastric bypass (GBP) operation in spontaneous rats with type 2 diabetes mellitus(GK rats) and to elucidate the mechanisms of GBP in improving insulin resistance.

METHODSThirty male GK rats aged 8 weeks were randomly divided into 3 groups according to the table of random number: the operation group (GBP, 10 rats), the sham operation group (the same sites were cut off as GBP and end to end anastomosis was performed in site, 10 rats) and the diet pairing group (the same kind and weight dieting as the operation group, 10 rats), besides 10 male SD rats aged 8 weeks were used as blank control group (free eating and drinking). Four weeks before and after operation, levels of fasting blood glucose(FPG) and fasting insulin(FINS) were measured, HOMA-IR was calculated respectively, and compared among 4 groups. Then rats were decapitated to retrieve the omentum. Expressions of adipic IR-β and IRS-1 protein were detected by Western blot.

RESULTSCompared with the preoperative levels, the FPG and HOMA-IR decreased significantly 4 weeks after surgery in operation group [(5.13±0.22) vs. (11.73±0.37) mmol/L, 2.16±0.18 vs. 5.10±0.29, P<0.05), reaching the level of blank control group(P>0.05). FINS showed no obvious change in these 4 groups after operation(all P>0.05). Expressions of IR-β and IRS-1 were significantly higher in operation group than those in other 3 groups 4 weeks after the operation(all P<0.05).

CONCLUSIONSExpressions of adipic IR-β and IRS-1 in insulin signal transmission of rats with type 2 diabetes mellitus after GBP are up-regulated, meanwhile insulin resistance can be improved and insulin sensibility increases.

Animals ; Body Weight ; Diabetes Mellitus, Type 2 ; Gastric Bypass ; Insulin ; Insulin Receptor Substrate Proteins ; Insulin Resistance ; Male ; Rats ; Receptor, Insulin ; Up-Regulation

Insulin autoimmune syndrome is an uncommon cause of hypoglycemia. According to the type of antibody, it can be classified as caused by insulin or insulin receptor autoantibodies. Generally, insulin autoimmune syndrome develops following exposure to exogenous insulin or sulfhydryl medications, although insulin or insulin receptor antibody may also occur spontaneously. We treated a 54-year-old woman who developed spontaneous hypoglycemia. The patient had repeated hypoglycemia despite the infusion of dextrose solution. Her serum insulin, c-peptide, and insulin autoantibody were elevated, even during the hypoglycemic periods. Insulin receptor autoantibody and HLA-cw4/B62/DR4 were positive. After steroid and diazoxide treatment, the hypoglycemic symptoms improved gradually. No further hypoglycemic episodes occurred after tapering the medication over 1 year. We present a case of insulin autoimmune syndrome with positive insulin and insulin receptor autoantibodies.
Autoantibodies ; C-Peptide ; Diazoxide ; Female ; Glucose ; Humans ; Hypoglycemia ; Insulin ; Middle Aged ; Receptor, Insulin

Hyperinsulinemic hypoglycemia in the absence of exogenous insulin use is caused by disorders such as insulinoma, diffuse beta-cell hyperplasia/nesidioblastosis, and autoimmune hypoglycemia. Nesidioblastosis is a rare cause of hypoglycemia in adults, accounting for 0.5~7.0% of organic hyperinsulinemia cases. Although pancreatic resection is considered the best treatment modality for curing nesidioblastosis, there is no consensus regarding the indications for and extent of the surgery due to its high risk and complication rate. A 75-year-old woman presented with an altered mental state, a mass suspected of being an insulinoma, and insulin receptor antibodies. The patient underwent surgery because of recurrent life-threatening hypoglycemia. Postoperative pathology of her pancreas revealed nesidioblastosis.
Accounting ; Adult ; Aged ; Antibodies ; Consensus ; Female ; Humans ; Hyperinsulinism ; Hypoglycemia ; Insulin ; Insulinoma ; Nesidioblastosis ; Pancreas ; Receptor, Insulin