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Biomedical subjects

Y Oka

Publications and source records attributed to Y Oka.

At least 163 records · Page 9Linked to original sources
PubMed1998

Granulocyte colony-stimulating factor (G-CSF) dependent hematopoiesis with monosomy 7 in a patient with severe aplastic anemia after ATG/CsA/G-CSF combined therapy.

We report a case of secondary myelodysplastic syndrome (MDS) with monosomy 7, which evolved from severe aplastic anemia (SAA) after long-term use of granulocyte colony-stimulating factor (G-CSF). A 36 year old female was admitted for detailed examination and treatment of pancytopenia. SAA was diagnosed based on hypoplastic bone marrow and a normal chromosome study. She was treated with anti-thymocyte globulin (ATG), ciclosporin A (CsA) and G-CSF, which resulted in gradual improvement of not only the myeloid but also the erythroid-megakaryocyte series. However, bone marrow dysplasia with monosomy 7 was observed after 7 months of a combination therapy of immunosuppressant and G-CSF, which prompted the discontinuation of G-CSF administration. Thereafter, bone marrow hypoplasia gradually progressed, resulting in a second aplastic crisis. During this process, the proportion of marrow cells showing monosomy 7 decreased, and the proportion with normal karyotype increased. Re-administration of G-CSF induced a trilineage, though dysplastic, hematological response; but the monosomy 7 positive population increased again. These observations indicated the presence of G-CSF dependent hematopoiesis associated with monosomy 7 in this patient. Although many G-CSF related MDS/AML cases with this leukemia-specific abnormal karyotype have been reported with emphasis on the harmful effects of G-CSF, G-CSF was useful even after the appearance of monosomy 7 as a means of avoiding life-threatening infection in this patient.

Adult↗
PubMed1998

A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).

Wolfram syndrome (WFS; OMIM 222300) is an autosomal recessive neurodegenerative disorder defined by young-onset non-immune insulin-dependent diabetes mellitus and progressive optic atrophy. Linkage to markers on chromosome 4p was confirmed in five families. On the basis of meiotic recombinants and disease-associated haplotypes, the WFS gene was localized to a BAC/P1 contig of less than 250 kb. Mutations in a novel gene (WFS1) encoding a putative transmembrane protein were found in all affected individuals in six WFS families, and these mutations were associated with the disease phenotype. WFS1 appears to function in survival of islet beta-cells and neurons.

Adult↗
PubMed1998

Insulin secretion from isolated rat islets induced by the novel hypoglycemic agent A-4166, a derivative of D-phenylalanine.

A derivative of D-phenylalanine, A-4166, reportedly evokes a more rapid and short-lived hypoglycemic action in vivo than any of the currently available sulfonylureas. This novel oral hypoglycemic agent is structurally different from sulfonylureas. Therefore, studies were designed to elucidate the mechanisms by which A-4166 stimulates insulin secretion. Insulin release from incubated or perifused rat islets was dose-dependently stimulated by 10 to 200 mumol/l A-4166, in the presence of 2.8 mmol/l glucose. Both A-4166 and tolbutamide evoke a prompt rise in insulin secretion followed by a sustained gradually decreasing release from perfused islets in the presence of low glucose, although A-4166 appeared to be more sensitive than tolbutamide to subthreshold glucose concentration. Diazoxide abolished the initial release and blunted sustained release. Removing calcium from the perifusate abolished insulin release within 15 minutes. A-4166 inhibited [3H]-glibenclamide binding to HIT cell membranes and 86Rb efflux from ATP-depleted or diazoxide-treated cells. These results suggest that the insulin release induced by A-4166 is relevant to this agent occupying the tolbutamide binding sites. Therefore, one possible mechanism accounting for the more rapid and short-lived hypoglycemic action of A-4166 in vivo, as compared with tolbutamide, may involve the reported differences in the bioavailability of A-4166.

ATP-Binding Cassette Transporters↗
PubMed1998

Cellular uptake properties of oligonucleotides in LLC-PK1 renal epithelial cells.

The objective of this study was to clarify the renal uptake characteristics of oligonucleotides at a cellular level using LLC-PK1 renal epithelial cells derived from the proximal tubule. The association of [35S]-labeled 20-mer phosphodiester (PO) and phosphorothioate (PS) oligonucleotides with the monolayers of polarized LLC-PK1 cells cultured on polycarbonate filter was characterized after apical or basolateral application. The cellular association of PO and PS at both apical and basolateral membranes was time dependent and temperature dependent, and the apparent association amount of PS was larger than that of PO. The PO and PS association after apical application was saturable, with the apparent Km and Vmax values determined to be 5.4 microM and 0.14 nmol/mg protein for PO and 0.22 microM and 0.11 nmol/mg protein for PS, respectively. In contrast, almost linear kinetics were observed after basolateral application within a tested concentration range. The association was inhibited significantly by sodium azide and chloroquine, suggesting that an energy-dependent endocytotic process was involved. Internalization and subsequent transport to endosome and lysosome compartments of FITC-labeled oligonucleotides were shown by confocal laser scanning microscopy. The present study has demonstrated that both types of oligonucleotides are taken up by LLC-PK1 cells from both apical and basolateral surfaces probably via an endocytosis mechanism.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1998

Interplay of signal mediators of decapentaplegic (Dpp): molecular characterization of mothers against dpp, Medea, and daughters against dpp.

Decapentaplegic (Dpp) plays an essential role in Drosophila development, and analyses of the Dpp signaling pathway have contributed greatly to understanding of the actions of the TGF-beta superfamily. Intracellular signaling of the TGF-beta superfamily is mediated by Smad proteins, which are now grouped into three classes. Two Smads have been identified in Drosophila. Mothers against dpp (Mad) is a pathway-specific Smad, whereas Daughters against dpp (Dad) is an inhibitory Smad genetically shown to antagonize Dpp signaling. Here we report the identification of a common mediator Smad in Drosophila, which is closely related to human Smad4. Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. Dad stably associates with Tkv and thereby inhibits Tkv-induced Mad phosphorylation. Dad also blocks hetero-oligomerization and nuclear translocation of Mad. We also show that Mad exists as a monomer in the absence of Tkv stimulation. Tkv induces homo-oligomerization of Mad, and Dad inhibits this step. Finally, we propose a model for Dpp signaling by Drosophila Smad proteins.

Amino Acid Sequence↗
PubMed1998

Effects of the lazaroid, tirilazad mesylate, on sepsis-induced acute lung injury in minipigs.

OBJECTIVE: To assess the effects of the lazaroid, tirilazad mesylate, a potent lipid peroxidation inhibitor, in an animal model of Pseudomonas sepsis. DESIGN: Comparison of four experimental groups: a) saline control; b) Pseudomonas sepsis control; c) tirilazad mesylate control; and d) sepsis with tirilazad mesylate pre treatment. SETTING: University animal laboratory. SUBJECTS: Hanford minipigs (20 to 25 kg), anesthetized with pentobarbital and mechanically ventilated on an FIO2 of 0.4. INTERVENTIONS: Sepsis was induced by infusing Pseudomonas aeruginosa at 1 x 10(6) colony-forming units/kg/min over 120 mins. The tirilazad mesylate-treated group received a 5-mg/kg bolus 30 mins before, and a 3-mg/kg bolus 3 hrs after, the onset of sepsis. Hemodynamics, PaO2, and neutrophil counts were measured for 6 hrs. Thiobarbituric acid reactive material (TBARM) in tissue (lung, liver, and intestine), lung wet/dry weight ratio, lung myeloperoxidase activity, plasma tumor necrosis factor (TNF)-alpha concentrations, protein content, and percent neutrophils in bronchoalveolar lavage fluid were evaluated at the time the animals were killed (6 hrs). MEASUREMENTS AND MAIN RESULTS: Sepsis induced significant systemic hypotension, pulmonary hypertension, hypoxemia, and neutropenia. Sepsis also significantly increased TBARM content, lung wet/dry weight ratio, myeloperoxidase activity, plasma TNF-alpha concentrations, and bronchoalveolar lavage neutrophil percentage. Treatment with tirilazad mesylate significantly attenuated hypoxemia and decreased TBARM content, lung wet/dry weight ratio, myeloperoxidase activity, bronchoalveolar lavage protein, and bronchoalveolar lavage neutrophil percentage, but did not affect sepsis-induced hemodynamics, including systemic hypotension and pulmonary hypertension, plasma TNF-alpha concentrations, or neutropenia. CONCLUSIONS: Pretreatment with the tirilazad mesylate did not change P. aeruginosa sepsis-induced hemodynamic consequences. However, tirilazad mesylate attenuated sepsis-induced acute lung injury.

Animals↗
PubMed1998

Cerebral blood flow measurement as an indicator for an indirect revascularization procedure for adult patients with moyamoya disease.

OBJECTIVE: Some adult patients with moyamoya disease have been treated successfully by indirect revascularization alone, although surgical indications and hemodynamic changes for these patients have not been fully explored. To examine surgical indications for this procedure, we studied the regional cerebral blood flow (rCBF) and angiographic findings in adult patients with moyamoya disease preoperatively and postoperatively. METHODS: On 17 hemispheric sides of 12 adult patients with moyamoya disease treated surgically with a combination of various indirect procedures, mainly by encephaloduroarteriosynangiosis, we retrospectively evaluated changes in rCBF using xenon-133 single photon emission computed tomography, angiographic collateral formation, and clinical results. RESULTS: Preoperatively, the rCBF values in the cortices at the bypass site at rest and after acetazolamide loading were lower than normal. The rCBF values were significantly increased after revascularization, approaching normal, except for incomplete recovery of vascular reactivity. The extent of postoperative neovascularization from implanted tissues fed by the external carotid artery system was more developed, in parallel with the preoperative decrease in resting and loading rCBF values. One-third of the operated sides exhibiting both a low rCBF at rest and impaired vascular reactivity in the noninfarcted cortices achieved good revascularization over two-thirds of the middle cerebral artery territory, accompanied by rCBF improvement and moyamoya vessel regression. Enough potential for neovascularization in the noninfarcted cortices was indicated that the resting rCBF was lower than 50 ml/100 g per minute (below the normal value by 2 standard deviations) and did not increase more than that value after loading, even in a 40-year-old patient who presented with a hemorrhage. Clinically, 11 patients (92%) had good results at the 4-year follow-up, whereas 1 patient (8%) with unsatisfactory neovascularization and a lesser extent of moyamoya vessel reduction experienced rebleeding. CONCLUSION: We conclude that for the surgical treatment of adult patients with moyamoya disease, indirect procedures, mainly encephaloduroarteriosynangiosis, are recommended for patients with lower rCBF and no or negative vascular reactivity in the noninfarcted cortices, as well as for those who have no indication for the direct procedure. It is possible to determine these indications by a xenon-133 inhalation single photon emission computed tomographic study including an acetazolamide challenge test.

Adolescent↗
PubMed1998

Coexistence of chronic myelogenous leukemia and multiple myeloma. Case report and review of the literature.

A case report of simultaneous presentation of chronic myelogenous leukemia (CML) and multiple myeloma (MM) in a 72-year-old female is described. Our case was typical of Ph1-positive and chimeric bcr-abl messenger RNA-positive CML. Furthermore, a marked IgG (kappa-type) paraproteinemia was present. Fluorescence in situ hybridization showed that 97% of marrow nucleated cells were positive for bcr-abl fusion signal, when myeloma cells in the bone marrow amounted to 19.0%. In the literature survey, 4 similar cases with coexistence of CML and MM have been identified.

Aged↗
PubMed1998

Altered expression levels and impaired steps in the pathway to phosphatidylinositol 3-kinase activation via insulin receptor substrates 1 and 2 in Zucker fatty rats.

To elucidate the mechanism of obesity-related insulin resistance, we investigated the impaired steps in the processes of phosphatidylinositol (PI) 3-kinase activation through binding with insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in liver and muscle of Zucker fatty rats. The expressions of IRS-1 and IRS-2 were shown to be downregulated in both liver and muscle in fatty rats (hepatic IRS-1, 83%; hepatic IRS-2, 45%; muscle IRS-1, 60%; muscle IRS-2, 78%), resulting in decreased tyrosine phosphorylation in response to insulin stimulation. Despite the decrease in the tyrosine phosphorylation levels of hepatic IRS-1 and IRS-2 being mild to moderate, associated PI 3-kinase activities were dramatically decreased in fatty rats (IRS-1, 14%; IRS-2, 10%), which may suggest alteration in the sites of phosphorylated tyrosine residues of hepatic IRS-1 and IRS-2. In addition, we demonstrated that the expressions of p85alpha and p55alpha regulatory subunits of PI 3-kinase were reduced (p85alpha, 67%; p55alpha, 54%), and that the p50alpha regulatory subunit was markedly upregulated (176%) in the livers of fatty rats without apparent alterations in expressions of the catalytic subunits p110alpha and p110beta. These alterations may reflect the obesity-related insulin resistance commonly observed in human NIDDM.

Albumins↗
PubMed1998

Identification and functional analysis of sulfonylurea receptor 1 variants in Japanese patients with NIDDM.

The sulfonylurea receptor 1 (SUR1) is an essential regulatory subunit of the beta-cell ATP-sensitive K+ channel (K[ATP]). The possible role of SUR1 gene mutation(s) in the development of NIDDM remains controversial as both a positive association and negative linkage results have been reported. Therefore, we examined the SUR1 gene at the single nucleotide level with single strand conformation polymorphism analysis in 100 Japanese NIDDM patients. We identified a total of five amino acid substitutions and 17 silent mutations by examining all 39 exons of this gene. Two rare novel mutations, D811N in exon 20 and R835C in exon 21, were identified in the first nucleotide-binding fold (NBF), a functionally important region of SUR1, in one patient each, both heterozygotes. To analyze possible functional alterations, we reconstituted the mutant K(ATP) by coexpressing beta-cell inward rectifier (BIR) (Kir 6.2), a channel subunit of K(ATP), and mutant SUR1 in HEK293T and COS-7 cells. As demonstrated by the patch clamp technique and rubidium (Rb+) efflux studies, neither mutation alters the properties of channel activities. Two other rare missense mutations, R275Q in exon 6 and V560M in exon 12, were also identified. The R275Q substitution was not found in 67 control subjects, and V560M was present in three control subjects. Neither of these substitutions appeared to cosegregate with NIDDM in the probands' families. A previously reported S1370A substitution located in the second NBF was also common in the Japanese subjects (allelic frequency 0.37), and was found at an equal frequency in nondiabetic control subjects. In conclusion, SUR1 mutations impairing K(ATP) function do not appear to be major determinants of NIDDM susceptibility in Japanese.

ATP-Binding Cassette Transporters↗
PubMed1998

Mobile PCIS: point-of-care information systems with portable terminals.

We have developed a Point-of-Care Information System (PCIS) that uses portable terminals and supports the entire loop of daily nursing work for the first time. Nursing work includes a great deal of indirect nursing work, such as documenting patient information, conferring with other health-care providers, and so on, as well as direct patient care. The time needed for this indirect work often exceeds the time actually spent directly caring for patients and needs to be reduced. Our system was developed with the goal of doing this to make nursing work more efficient. The system consists of personal digital assistants (PDAs) that nurses carry in the hospital wards and a server computer located in the nursing station. The system has three main functions: 1) Data Browsing provides patient information such as a brief history, vital-sign charts, and handwritten notes; 2) Schedule Planning helps nurses organize doctors' instructions and make To-do lists for the day; and 3) Care Management reminds nurses when they should execute the doctors' orders and provides tools for data entry. These three functions cover the entire loop of daily nursing work. The PDAs and the server computer can share up-to-date information by data transmission through telephone lines (low-power cellular phones can be used), infrared devices, or RS-232C cables. Results from a preliminary hospital evaluation showed that use of the system can reduce the time needed for nursing documentation by 60% (a 10% saving of a nurse's total working time), and that more than 80% of the nurses who used the system felt it would make nursing work more efficient.

Attitude to Computers↗
PubMed1998

Debridement arthroplasty for osteoarthritis of the elbow.

For treatment of osteoarthritis of the elbow, the authors use debridement arthroplasty with a medial or lateral approach. Thirty-eight elbows in 36 patients treated with this procedure were examined. The age of the patients ranged from 20 to 71 years, with a mean age of 41.7 years. Cubital tunnel syndrome was present in 16 of the 38 (42%) elbows. The operations were performed through a lateral approach in four elbows, a lateral approach with medial skin incision for ulnar nerve neurolysis in 16 elbows, a medial approach in 10 elbows, and a medial plus a lateral approach in eight elbows. The followup ranged from 2 years to 12.1 years, with an average of 5.9 years. Complete pain relief or minimal elbow pain was reported in 95% of patients who had surgical treatment. The average gain in motion was 6 degrees extension and 18 degrees flexion. Results for the various surgical approaches did not show a statistically significant difference. Recurrence of bony spurs and ridges was analyzed additionally in 18 selected patients who could be observed more than 5 years after surgery (range, 5-12 years). Redevelopment of bony spurs on the coronoid process and olecranon tip occurred in all 18 patients, but those changes were graded as mild in 13 (74%) patients and moderate in five (16%) patients and were accompanied by no pain or slight pain. Elbow arthroplasty as used by the authors produces stable and reliable results for relief of pain, gains in range of motion, and the absence of recurrence of significant osteoarthritis.

Adult↗
PubMed1998

[Impaired coronary flow reserve due to long-term smoking recovers after quitting].

Cigarette smoking is a major risk factor for coronary artery disease. The present study examined whether impaired coronary flow reserve by smoking can be recovered by quitting. Coronary flow velocity was measured by Doppler guide wire during coronary angiography and coronary flow reserve was determined by injecting 10 mg intracoronary papaverine in 45 patients who were present or former smokers. Twenty-three patients were smoking more than 800 cigarettes/day x years and 22 patients less than 800, and 13 patients had smoked more than 800 but had quit smoking at least for 5 years. None of the patients had any significant coronary stenosis in the left anterior descending artery where the Doppler probe was positioned, nor any coronary risk factors except smoking. Twenty-six non-smokers served as control subjects. There was no difference in the coronary flow reserve between controls and light smokers (3.3 +/- 0.7 vs 3.3 +/- 1.0), but it was significantly reduced in heavy smokers (2.6 +/- 0.8) compared to controls or light smokers (p < 0.05, p < 0.05, respectively), There was no significant difference in coronary flow reserve between controls, light smokers and ex-smokers (3.3 +/- 1.2). These results suggest that the deteriorating effect on the coronary flow reserve by smoking is corrected after its cessation.

Aged↗
PubMed1998

Tumor recurrence in patients with early gastric cancer: a clinicopathologic evaluation.

We conducted a retrospective study on 711 patients with early gastric cancer. Twenty-two patients (4.0%) developed recurrent disease and 21 died of recurrence during this study. One hundred and sixty-three patients died of unrelated or unknown causes. The recurrence patterns of 22 patients were as follows: hematogeneous metastasis to the liver in 11 patients, peritoneal dissemination in 3, recurrence in the remnant stomach in 3, and in the distant lymphonodes in 1. The mean survival period of patients with recurrent disease was 50.4 months, and 7 of these patients (31.8%) died more than 5 years after surgery. A retrospective clinicopathologic evaluation of the 22 patients and 526 patients without recurrence revealed significant differences between the two groups with respect to mean age at the time of surgery (62.5 years in the recurrent group vs 57.3 years in the nonrecurrent group), tumor size (41.2 vs 30.6 mm), depth of invasion (submucosal cancer: 19 vs 256), lymphnode metastasis (11 vs 48), lymphatic (11 vs 89) and venous (7 vs 18) invasion, and operative curability (curability B: 8 vs 48). Three patients with intramucosal cancer who died of hematogenous and/or peritoneal recurrence within 7 years after surgery had neither lymphnode metastasis nor lymphatic or venous invasion, suggesting that new techniques are needed for prediction of recurrent disease in patient with early gastric cancer.

Adult↗
PubMed1997

Leptin induces proliferation of pancreatic beta cell line MIN6 through activation of mitogen-activated protein kinase.

Leptin at 1-5 nM, the concentrations observed in obese subjects, caused an increase in the active form of mitogen-activated protein kinase (MAPK) that was accompanied by increased tyrosine phosphorylation of STAT-1 and STAT-3 in a mouse pancreatic beta cell line, MIN6. Leptin also increased DNA synthesis and cell viability in MIN6 cells based on the results of [3H]-thymidine incorporation and colorimetric MTT assay, respectively. The specific MAPK-inhibitor PD98059 blocked not only the MAPK activation but also the increment in DNA synthesis and cell viability caused by leptin. Thus, leptin stimulates both the MAPK and the Janus kinase (JAK)-STAT cascade as well as inducing proliferation through the MAPK cascade in MIN6 cells. This mechanism might account, at least in part, for obesity-induced pancreatic islet hypertrophy.

Animals↗
PubMed1997

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an islet substance serving as an intra-islet amplifier of glucose-induced insulin secretion in rats.

1. We examined whether pituitary adenylate cyclase-activating polypeptide with 38 or 27 residues (PACAP-38 or PACAP-27) serves as an intra-islet regulator of glucose-induced insulin secretion in rats. PACAP antiserum specific for PACAP-38 and PACAP-27 was used to neutralize the effect of endogenous PACAP in islets. PACAP release from islets was bioassayed using the response of cytosolic Ca2+ concentration ([Ca2+]i) in single beta-cells, monitored by dual-wavelength fura-2 microfluorometry. Expression of PACAP mRNA was studied by reverse transcription-polymerase chain reaction (RT-PCR), while expression of PACAP was studied by metabolic labelling and immunoblotting. Localization of PACAP receptors was studied immunohistochemically. 2. High glucose-stimulated insulin release from isolated islets was attenuated by PACAP antiserum but not by non-immune sera. 3. The islet incubation medium with high glucose (Med) possessed a capacity, which was neutralized by PACAP antiserum, to increase [Ca2+]i in beta-cells. PACAP antiserum also neutralized the [Ca2+]i-increasing action of synthetic PACAP-38 and PACAP-27, but not that of vasoactive intestinal polypeptide (VIP) and glucagon. 4. Both Med and synthetic PACAP increased [Ca2+]i in beta-cells only in the presence of stimulatory, but not basal, glucose concentrations. In contrast, ATP, a substance that is known to be released from beta-cells, increased [Ca2+]i in beta-cells at both and stimulatory glucose concentrations. 5. Expression of PACAP mRNA and biosynthesis of PACAP-38 were detected in islets and a beta-cell line, MIN6. 6. Immunoreactivity for PACAP-selective type-I receptor was observed in islets. 7. [Ca2+]i measurements combined with immunocytochemistry with insulin antiserum revealed a substantial population of glucose-unresponsive beta-cells, many of which were recruited by PACAP-38 into [Ca2+]i responses. 8. These results indicate that PACAP-38 is a novel islet substance that is synthesized and released by islet cells and then, in an autocrine and/or paracrine manner, potentiates and arouses beta-cell responses to glucose, thereby amplifying glucose-induced insulin secretion in islets.

Adenosine Triphosphate↗
PubMed1997

14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain.

Insulin binding to its receptor induces the phosphorylation of cytosolic substrates, insulin receptor substrate (IRS)-1 and IRS-2, which associate with several Src homology-2 domain-containing proteins. To identify unique IRS-1-binding proteins, we screened a human heart cDNA library with 32P-labeled recombinant IRS-1 and obtained two isoforms (epsilon and zeta) of the 14-3-3 protein family. 14-3-3 protein has been shown to associate with IRS-1 in L6 myotubes, HepG2 hepatoma cells, Chinese hamster ovary cells, and bovine brain tissue. IRS-2, a protein structurally similar to IRS-1, was also shown to form a complex with 14-3-3 protein using a baculovirus expression system. The amount of 14-3-3 protein associated with IRS-1 was not affected by insulin stimulation but was increased significantly by treatment with okadaic acid, a potent serine/threonine phosphatase inhibitor. Peptide inhibition experiments using phosphoserine-containing peptides of IRS-1 revealed that IRS-1 contains three putative binding sites for 14-3-3 protein (Ser-270, Ser-374, and Ser-641). Among these three, the motif around Ser-270 is located in the phosphotyrosine binding domain of IRS-1, which is responsible for the interaction with the insulin receptor. Indeed, a truncated mutant of IRS-1 consisting of only the phosphotyrosine binding domain retained the capacity to bind to 14-3-3 protein in vivo. Finally, the effect of 14-3-3 protein binding on the insulin-induced phosphorylation of IRS-1 was investigated. Phosphoamino acid analysis revealed that IRS-1 coimmunoprecipitated with anti-14-3-3 antibody to be weakly phosphorylated after insulin stimulation, on tyrosine as well as serine residues, compared with IRS-1 immunoprecipitated with anti-IRS-1 antibody. Thus, the association with 14-3-3 protein may play a role in the regulation of insulin sensitivity by interrupting the association between the insulin receptor and IRS-1.

14-3-3 Proteins↗