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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The platelet membrane insulin receptors of healthy and non-insulin dependent (type 2) diabetic patients were studied. Receptor number and affinity proved to be decreased in type 2 diabetes mellitus. The changes in platelet insulin receptor characteristics are in good correlation with the alterations reported in other tissues or cells. The possible role of these phenomena in the pathogenesis of disturbed platelet function in diabetics needs further investigation.
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PMID:Platelet insulin receptor determination in non-insulin dependent diabetes mellitus. 397 93

"Postreceptor" insulin resistance in persons with non-insulin-dependent diabetes (NIDDM) could be due to an intrinsic defect in insulin-sensitive pathways or to the action of a circulating inhibitor. Since evidence for the former is lacking, we have addressed the question of a circulating inhibitor by examining the effect of plasma and plasma extracts from NIDDM subjects on the lipogenic response of rat adipocytes to insulin. A majority (77%) of plasma samples (1:20 dilution) from unselected, treated NIDDM subjects (N = 69) inhibited insulin-stimulated conversion of 3-3H-glucose to 3H-lipid in rat adipocytes to a greater extent than did control samples (N = 24). The mean +/- SD inhibition by NIDDM plasma (81 +/- 21%) was significantly greater (P less than 0.01) than by control plasma (50 +/- 14%). Diabetic and, to a lesser degree, control plasma both caused a significant decrease in the maximal response of lipogenesis to insulin. Inhibitory activity was extracted into acid/ethanol, present in the flow of a Sep-pak C18 column, heat-stable (56 degrees C for 30 min [plasma], 80 degrees C for 30 min [acid/ethanol]), resistant to proteases, and dialyzable through 1000-dalton-mol wt exclusion dialysis tubing. The inhibition by NIDDM plasma or partially purified inhibitor could not be explained by the presence of insulin antibodies, insulin receptor antibodies, other inhibitors of insulin binding, or the concentrations of known counterregulatory factors. There was no correlation between inhibitory activity and plasma glucose (r = 0.26), insulin (r = 0.33), C-peptide (r = 0.26), or HbA1c (r = 0.26).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A postbinding inhibitor of insulin action. Increased concentrations in the plasma of non-insulin-dependent diabetic subjects. 637 53

To determine whether long-term sulfonylurea therapy ameliorates glucose homeostasis in patients with NIDDM predominantly by improving insulin secretion or by improving insulin action, we evaluated changes in fasting plasma glucose concentrations, intravenous glucose tolerance, glucose-stimulated insulin secretion, facilitation of glucose disposal by exogenous insulin, and erythrocyte insulin receptor binding before and after prolonged (congruent to 4 mo) administration of tolazamide to 18 patients with NIDDM. Before tolazamide administration, 15 patients had decreased insulin secretion (50 +/- 31 vs 577 +/- 176 microU/ml X 10 min in nondiabetic subjects, P less than 0.05) and insulin resistance (Km 166 +/- 31 vs 58 +/- 3 microU/ml in nondiabetic subjects, P less than 0.05; Vmax 7.3 +/- 0.6 vs 9.8 +/- 0.2 mg/kg/min in nondiabetic subjects, P less than 0.05), whereas the other three patients had comparably impaired insulin secretion (56 +/- 52 microU/ml X min) but were not insulin resistant (Km 70 +/- 6 microU/ml; Vmax 10.8 +/- 0.6 mg/kg/min). The insulin-resistant patients had fasting hyperinsulinemia (19 +/- 4 vs 11 +/- 1 microU/ml in nondiabetic subjects, P less than 0.05), decreased erythrocyte insulin receptor binding (4.8 +/- 0.4 vs 5.8 +/- 0.3%/1.6 X 10(9) cells in nondiabetic subjects, P less than 0.05), and impairment in both insulin-induced suppression of glucose production (Km 97 +/- 31 vs 21 +/- 7 microU/ml in nondiabetic subjects, P less than 0.05), and insulin-induced stimulation of glucose utilization (Km and Vmax 176 +/- 29 microU/ml and 5.8 +/- 0.7 mg/kg/min vs 50 +/- 2 microU/ml and 9.1 +/- 0.6 mg/kg/min in nondiabetic subjects, both P less than 0.05). The nonresistant patients were not hyperinsulinemic (12 +/- micU/ml), had normal insulin receptor binding (5.9 +/- 0.5%/1.6 X 10(9) cells), and were less hyperglycemic than the insulin-resistant patients (128 +/- 11 vs 181 +/- 12 mg/dl, P less than 0.05). After tolazamide administration, both the early phase of glucose-induced insulin secretion (56 +/- 52 vs 141 +/- 68 microU/ml . 10 min) and insulin binding (5.9 +/- 0.5 vs 7.0 +/- 0.5%/1.6 X 10(9) cells) increased in all three nonresistant patients, but there was no consistent improvement in fasting hyperglycemia (128 +/- 11 vs 130 +/- 24 mg/dl), intravenous glucose tolerance (Kivgtt 0.77 +/- 0.18 vs 0.89 +/- 0.29%/min), or facilitation of glucose disposal by insulin (Km 70 +/- 5 vs 64 +/- 5 microU/ml; Vmax 10.8 +/- 0.6 vs 10.1 +/- 0.2 mg/kg/min).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prolonged sulfonylurea administration decreases insulin resistance and increases insulin secretion in non-insulin-dependent diabetes mellitus: evidence for improved insulin action at a postreceptor site in hepatic as well as extrahepatic tissues. 637 34

We studied the effect of acute short-term exercise on insulin binding to erythrocytes in plasma with non-insulin dependent diabetes mellitus and normal controls. In the normal controls, insulin binding was increased immediately after the exercise and returned to the basal level at 30 min after the exercise. This increase was due to an affinity change without any change in the insulin receptor number. In contrast, insulin binding tended to decrease in the diabetics after the exercise, and this change was due to a decreased affinity without any change in the number of insulin receptors. These results indicate that the control mechanism of insulin receptor affinity in response to exercise is different in non-insulin dependent diabetics and normals.
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PMID:Effect of acute exercise on insulin binding to erythrocytes in type II diabetes. 676 63

Obese-hyperglycemic mice (genotype ob/ob) have hyperglycemia, hyperinsulinemia, increased resistance to insulin action and decreased insulin receptors on their liver, fat cell and muscle plasma membranes. Hypoglycemic sulfonylureas are reported to improve diabetic control by decreasing the insulin resistance of subjects with Type II diabetes mellitus: however, it is not clear if their mechanism is to increase plasma membrane insulin receptors or to decrease post-receptor insulin resistance. In this study we treated obese-hyperglycemic mice and their normal weight litter mates with the oral hypoglycemic sulfonylurea tolbutamide for 28 to 34 weeks. Tolbutamide administration to normal mice resulted in the following changes that were indicative of increased insulin action: (1) increased body weight; (2) increased epididymal fat-pad weight; (3) increased 2-deoxyglucose transport into the intact diaphragm muscle preparation. There was no alteration in plasma glucose, plasma insulin or pancreatic insulin content suggesting that the tolbutamide effect was an extrapancreatic effect that was probably not mediated by increased insulin secretion. There was no change in the insulin receptor number or affinity of liver cell membranes prepared from tolbutamide treated mice supporting the notion that the extrapancreatic effect of tolbutamide may occur at a post-insulin receptor location. In contrast to the normal mice, tolbutamide did not increase the body weight, epididymal fat pad weight, the already increased 2-deoxyglucose transport into diaphragm muscle or the decreased number of insulin receptors on hepatic plasma membranes. The tolbutamide caused a striking decrease in pancreatic insulin concentration and degranulation of the islets in obese but not normal mice. This is compatible with previous information that the obese mice have abnormal islets that are not under the normal feed-back control of ambient insulin concentration as are the islets of normal mice. We conclude that tolbutamide potentiates insulin action in normal, but not obese, mice and that this potentiation may be due to a post-insulin receptor action.
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PMID:Effect of chronic tolbutamide administration on normal and obese-hyperglycemic mice: evidence for post-receptor potentiation of insulin action. 704 79

Once thought to be solely a disease of insulin deficiency, diabetes mellitus now is recognized as a disorder with multiple pathogenetic mechanisms. Newer terminology identifies those uncommon patients with true insulin deficiency as having insulin-dependent diabetes (IDDM), while the majority of patients with diabetes have some residual insulin secretion but may have a disorder of insulin receptor number or affinity. These patients have non-insulin dependent diabetes (NIDDM). Other patients may have gestational diabetes, impaired glucose tolerance, a potential for glucose intolerance, or a previous history of diabetes. A few patients will have diabetes secondary to a known cause, such as pancreatitis or Cushing's syndrome. Understanding this nosological approach to diabetes should enhance the clinician's decisions regarding therapy.
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PMID:Classification and pathogenesis of the diabetes syndrome: a historical perspective. 705 Feb 15

Protein-tyrosine phosphatases (PTPases) have been postulated to balance the steady-state phosphorylation and the activation state of the insulin receptor and its substrate proteins. To explore whether PTP1B, a widely expressed, non-receptor-type PTPase, regulates insulin signaling, we used osmotic shock to load rat KRC-7 hepatoma cells with affinity-purified neutralizing antibodies that immunoprecipitate and inactivate the enzymatic activity of recombinant rat PTP1B in vitro. In cells loaded with PTP1B antibody, insulin-stimulated DNA synthesis and phosphatidylinositol 3'-kinase activity were increased by 42% and 38%, respectively, compared with control cells loaded with preimmune IgG (p < 0.005). In order to characterize the potential site(s) of action of PTP1B in insulin signaling, we also determined that insulin-stimulated receptor autophosphorylation and insulin receptor substrate 1 tyrosine phosphorylation were increased 2.2- and 2.0-fold, respectively, and that insulin-stimulated receptor kinase activity toward an exogenous peptide substrate was increased by 57% in the PTP1B antibody-loaded cells. Osmotic loading did not alter the cellular content of PTP1B protein, suggesting that the antibody acts in the cell by sterically blocking catalytic interactions between PTP1B and its physiological substrates. These studies demonstrate that PTP1B has a role in the negative regulation of insulin signaling and acts, at least in part, directly at the level of the insulin receptor. These results also show that insulin signaling can be enhanced by the inhibition of specific PTPases, a maneuver that has potential clinical relevance in the treatment of insulin resistance and Type II diabetes mellitus.
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PMID:Osmotic loading of neutralizing antibodies demonstrates a role for protein-tyrosine phosphatase 1B in negative regulation of the insulin action pathway. 754 90

To understand the effects of the levels of blood lipids and albumin on insulin receptor binding before and after acute exercise, we measured insulin binding to erythrocyt membrane before and after 30 minutes moderate exercise in thirty-eight non-obese noninsulin-dependent diabetics (NIDDM) and thirty-seven normal subjects. The correlations between parameters of insulin receptor and blood lipids and albumin were also studied. The results showed that before acute exercise, the level of high-binding-affinity (K1) was significantly correlated with that of total cholesterol (r = -0.473, P = 0.013), and albumin (r = -0.483, P = 0.011). The low-binding-affinity (K2) was significantly correlated with that of triglycerides (r = 0.503, P = 0.008) and high-density-lipoprotein (HDL) cholesterol (r = -0.480, P = 0.011). After acute exercise, no significant correlations between the parameters of insulin receptor, blood lipids and albumin were found. These suggest that blood lipids and albumin are important influential factors for affinities of insulin receptor.
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PMID:[Correlative study of erythrocyte membrane insulin receptor with blood lipids and albumin in non-obese noninsulin-dependent diabetics (NIDDM) patients before and after exercise]. 758 73

Chromosome 19 is short but has higher relative density of genes than other chromosomes. Increasing number of the genes coding for proteins implicated in the pathogenesis of various human diseases have been mapped on chromosome 19. Mutations of low density lipoprotein receptor (LDL-R) result in one of the most frequent mendelian inherited disorder-familial hypercholesterolemia. Mutations of insulin receptor (INSR) are causative for rare syndromes of insulin resistance and some of non insulin dependent diabetes mellitus (NIDDM). Erythropoietin receptor (EPOR) mutations are causative for rare primary familial and congenital polycythemias (PFCP). Defects of one of the largest gene in the human genome RYR 1 (ryanodine receptor gene) (> 240 kb in size) accounts for majority of malignant hyperthermia (MH) and central core disease (CCD). All these disorders represent group of receptor diseases. The amplification of GCT trinucleotide repeats in myotonic dystrophy protein kinase (DMPK) gene is causative for myotonic dystrophy (DM) and represents a new class of human gene mutations: trinucleotide repeat mutations. Apolipoprotein E (APOE) locus plays a role in pathogenesis of the late onset familial Alzheimer's disease. Translocation of EA2 gene which encodes two helix-loop-helix (HLH) transcription proteins and its fusion with PBXI or hepatic leukemia factor (HLF) leads to the leukemogenesis in subgroup of ALL. Interestingly adeno-associated virus (AAV), currently widely used as vector for gene therapy has unique capability of specific integration into human chromosome 19q.
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PMID:Human genome--chromosome no. 19. 758 75

The tyrosine kinase activity of insulin receptor isolated from the skeletal muscle of NIDDM patients has previously been found to be decreased compared with the activity of receptor from nondiabetic subjects but the mechanism underlying this defect is unknown. Phosphorylation of receptor serine/threonine residues has been proposed to exert an inhibitory influence on receptor tyrosine kinase activity and Ser 1327 and Thr 1348 have been identified as specific sites of phosphorylation in the insulin receptor COOH terminal domain. To address the potential negative regulatory role of phosphorylation of these residues in vivo, we assessed the extent of phosphorylation of each site in insulin receptor isolated from the skeletal muscle of 12 NIDDM patients and 13 nondiabetic, control subjects. Phosphorylation of Ser 1327 and Thr 1348 was determined using antibodies that specifically recognize insulin receptor phosphorylated at these sites. In addition, a phosphotyrosine-specific antibody was used to monitor receptor tyrosine phosphorylation. The extent of insulin-induced tyrosine autophosphorylation was decreased in receptor isolated from diabetic versus nondiabetic muscle, thus confirming earlier reports. In contrast, there was no significant difference in the extent of phosphorylation of either Ser 1327 or Thr 1348 in receptor isolated from diabetic or nondiabetic muscle as assessed by immunoprecipitation (Ser 1327: 5.6 +/- 1.6% diabetics vs. 4.7 +/- 2.0% control; Thr 1348: 3.8 +/- 1.0% diabetics vs. 3.2 +/- 1.2% control). Moreover, within each group there was no correlation between the level of tyrosine kinase activity and the extent of serine/threonine phosphorylation. It is concluded that the stoichiometry of serine/threonine phosphorylation of insulin receptor in vivo is low, and that increased phosphorylation of Ser 1327 or Thr 1348 is not responsible for the decreased insulin receptor tyrosine kinase activity observed in the skeletal muscle of NIDDM patients.
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PMID:Mechanism of insulin receptor kinase inhibition in non-insulin-dependent diabetes mellitus patients. Phosphorylation of serine 1327 or threonine 1348 is unaltered. 761 33


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