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G Inoue

Publications and source records attributed to G Inoue.

At least 37 records · Page 2Linked to original sources
PubMed1999

Down regulation of peroxisome proliferator-activated receptorgamma expression by inflammatory cytokines and its reversal by thiazolidinediones.

AIMS/HYPOTHESIS: Previous studies show that inflammatory cytokines play a part in the development of insulin resistance. Thiazolidinediones were developed as insulin-sensitizing drugs and are ligands for the peroxisome proliferator-activated receptory (PPARgamma). We hypothesized that the anti-diabetic mechanism of thiazolidinediones depends on the quantity of PPARgamma in the insulin resistant state in which inflammatory cytokines play a part. METHODS: We isolated rat PPARgamma1 and gamma2 cDNAs and examined effects of various cytokines and thiazolidinediones on PPARgamma mRNA expression in rat mature adipocytes. RESULTS: Various inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), IL-1beta, IL-6 and leukaemia inhibitory factor decreased PPARgamma mRNA expression. In addition, hydrogen peroxide, lysophosphatidylcholine or phorbol 12-myristate 13-acetate also decreased the expression of PPARgamma. The suppression of PPARgamma mRNA expression caused by 10 nmol/l of TNF-alpha was reversed 60% and 55% by treatment with 10(-4) mol/l of troglitazone and 10(-4) mol/l of pioglitazone, respectively. The suppression of glucose transporter 4 mRNA expression caused by TNF-alpha was also reversed by thiazolidinediones. Associated with the change of PPARgamma mRNA expression, troglitazone improved glucose uptake suppressed by TNF-alpha. CONCLUSION/INTERPRETATION: Our study suggests that inflammatory cytokines could be factors that regulate PPARgamma expression for possible modulation of insulin resistance. In addition, we speculate that the regulation of PPARgamma mRNA expression may contribute to the anti-diabetic mechanism of thiazolidinediones.

Adipocytes↗
PubMed1999

Thyrotropin decreases leptin production in rat adipocytes.

Leptin, which is secreted from adipocytes, has a role in the regulation of appetite and energy expenditure. The thyrotropin receptor (TSH-R) was recently found in adipocytes. We examined the effects of TSH on leptin production and lipolysis in rat epididymal adipocytes. TSH decreased the concentration of leptin in the medium time (approximately 24 hours)- and dose (approximately 10(-7) mol/L)-dependently (half-maximal inhibition [IC50] approximately 10(-9) mol/L). TSH also decreased the ob mRNA level approximately 55% in adipocytes. We confirmed the presence of TSH-R mRNA in the adipocytes by reverse transcription-polymerase chain reaction (RT-PCR). TSH stimulated glycerol release dose-dependently (IC50 approximately 10(-8) mol/L) in adipocytes. This TSH-induced glycerol release was further enhanced by adenosine deaminase (ADA). In summary, TSH reduced leptin production and stimulated lipolysis in rat epididymal adipocytes. Although the pathophysiological relevance of the regulation of leptin production and lipolysis by TSH is unknown, we speculate that TSH may affect the regulation of appetite and energy expenditure in pathophysiological states.

Adipocytes↗
PubMed1999

Hypertension and insulin resistance: role of peroxisome proliferator-activated receptor gamma.

1. Insulin resistance has been highlighted as a common causal factor for hypertension, hyperlipidaemia, diabetes mellitus and obesity, all of which are recognized to occur simultaneously, and a distinct clinical entity is defined as 'multiple risk factor syndrome'. 2. Recently, a new class of antidiabetic agents, thiazolidinediones (TZD) has been developed and has been shown to improve insulin resistance by binding and activating a nuclear receptor, peroxisome proliferator-activated receptor (PPAR) gamma. 3. cDNA of rat PPAR gamma 1 and gamma 2 were cloned and gene regulation of PPAR gamma in rat mature adipocytes was examined. Hydrogen peroxide, an oxygen radical, which is recognized to be the common intracellular signal for multiple risk factors, potently down-regulated PPAR gamma mRNA expression in rat mature adipocytes. 4. Tumour necrosis factor (TNF)-alpha, which is considered to play a role in obesity-induced non-insulin-dependent diabetes mellitus and to augment oxidative stress, also suppressed PPAR gamma expression. 5. Thiazolidinediones dose-dependently recovered TNF-alpha-induced down-regulation of PPAR gamma mRNA expression. 6. The modulation of PPAR gamma expression by TZD can be one mechanism for the improvement of insulin resistance by TZD. 7. Vascular tone and remodelling are controlled by several vasoactive autocrine/paracrine factors produced by endothelial cells in response to several vascular injury stimuli, including hypertension. The PPAR gamma gene transcript was detected in cultured endothelial cells. 8. The administration of TZD stimulated the endothelial secretion of type-C natriuretic peptide, which is one of the natriuretic peptide family and is demonstrated by us to act as a novel endothelium-derived relaxing peptide. 9. Concomitantly, TZD significantly suppressed the secretion of endothelin, a potent endothelium-derived vasoconstricting peptide. 10. Thiazolidinediones can affect vascular tone and growth by modulating the production of endothelium-derived vasoactive substances to influence occurrence and progression of hypertension and atherosclerosis.

Adipose Tissue↗
PubMed1999

Late treatment of unreduced perilunate dislocations.

Twenty-eight patients with perilunate dislocations that had been untreated for a minimum of 6 weeks after injury were assessed at a mean of 6.8 years after subsequent treatment. Treatment consisted of open reduction with or without internal fixation of the scaphoid in six patients, proximal row carpectomy in 16, total excision of the lunate in four, and carpal tunnel release and partial excision of the lunate in two. Open reduction yielded satisfactory results in cases of less than 2 months standing. We believe that proximal row carpectomy should be considered in the treatment of chronic perilunate dislocations in patients who are seen later than 2 months after injury, if the cartilage of the proximal pole of the capitate is well preserved. The results of lunate excision were less favourable.

Adolescent↗
PubMed1999

Complete dislocation of the trapezium. Case report.

A 24-year-old woman presented with complete, closed dislocation of the trapezium after a skiing accident. Treatment by closed reduction and fixation with a Kirschner wire gave an excellent clinical result with early return to full function. There were no radiological signs of arthrosis or avascular necrosis at 2 years follow-up.

Adult↗
PubMed1999

Glucose metabolism and insulin sensitivity in transgenic mice overexpressing leptin with lethal yellow agouti mutation: usefulness of leptin for the treatment of obesity-associated diabetes.

Leptin acts as an adipocyte-derived blood-borne satiety factor that can increase glucose metabolism. To elucidate the therapeutic implications of leptin for obesity-associated diabetes, we crossed transgenic skinny mice overexpressing leptin (Tg/+), which we have developed recently, and lethal yellow KKAy mice (Ay/+), a genetic model for obesity-diabetes syndrome, and examined the metabolic phenotypes of F1 animals. At 6 weeks of age, plasma leptin concentrations in Tg/+ mice with the Ay allele (Tg/+:Ay/+) were significantly higher than those in Ay/+ mice. Although no significant differences in body weight were noted among Tg/+:Ay/+ mice, Ay/+ mice, and their wild-type lean littermates (+/+), glucose and insulin tolerance tests revealed increased glucose tolerance and insulin sensitivity in Tg/+:Ay/+ compared with Ay/+ mice. However, at 12 weeks of age, when plasma leptin concentrations in Ay/+ mice were comparable to those in Tg/+:Ay/+ mice, Tg/+:Ay/+ mice developed obesity-diabetes syndrome similar to that of Ay/+ mice. Body weights of 12-week-old Tg/+:Ay/+ and Ay/+ mice were reduced to those of +/+ mice by a 3-week food restriction; when plasma leptin concentrations remained high in Tg/+:Ay/+ mice but were markedly reduced in Ay/+ and +/+ mice, glucose tolerance and insulin sensitivity in Tg/+:Ay/+ mice were markedly improved as compared with Ay/+ and +/+ mice. The present study demonstrates that hyperleptinemia can delay the onset of impaired glucose metabolism and accelerate the recovery from diabetes during caloric restriction in Tg/+:Ay/+ mice, thereby suggesting the potential usefulness of leptin in combination with a long-term caloric restriction for the treatment of obesity-associated diabetes.

Aging↗
PubMed1999

Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin.

Excess of body fat, or obesity, is a major health problem and confers a higher risk of cardiovascular and metabolic disorders such as diabetes, hypertension, and coronary heart disease. Leptin is an adipocyte-derived satiety factor that plays an important role in the regulation of energy homeostasis, and its synthesis and secretion are markedly increased in obese subjects. To explore the metabolic consequences of an increased amount of leptin on a long-term basis in vivo, we generated transgenic skinny mice with elevated plasma leptin concentrations comparable to those in obese subjects. Overexpression of leptin in the liver has resulted in complete disappearance of white and brown adipose tissue for a long period of time in mice. Transgenic skinny mice exhibit increased glucose metabolism accompanied by the activation of insulin signaling in the skeletal muscle and liver. They also show small-sized livers with a marked decrease in glycogen and lipid storage. The phenotypes are in striking contrast to those of recently reported animal models of lipoatrophic diabetes and patients with lipoatrophic diabetes with reduced amount of leptin. The present study provides evidence that leptin is an adipocyte-derived antidiabetic hormone in vivo and suggests its pathophysiologic and therapeutic implications in diabetes.

Animals↗
PubMed1998

Dynamics of insulin signaling in 3T3-L1 adipocytes. Differential compartmentalization and trafficking of insulin receptor substrate (IRS)-1 and IRS-2.

The ability of the insulin receptor to phosphorylate multiple substrates and their subcellular localization are two of the determinants that contribute to diversity of signaling. We find that insulin receptor substrate (IRS)-1 is 2-fold more concentrated in the intracellular membrane (IM) compartment than in cytosol, whereas IRS-2 is 2-fold more concentrated in cytosol than in IM. Insulin stimulation induces rapid tyrosine phosphorylation of both IRS-1 and IRS-2. This occurs mainly in the IM compartment, even though IRS-2 is located predominantly in cytosol. Furthermore, after insulin stimulation, both IRS-1 and IRS-2 translocate from IM to cytosol with a t1/2 of 3.5 min. Using an in vitro reconstitution assay, we have demonstrated an association between IRS-1 and internal membranes and have shown that the dissociation of IRS-1 from IM is dependent on serine/threonine phosphorylation of IM. By comparison, within 1 min after insulin stimulation, 40% of the total pool of the 85-kDa subunit of phosphatidylinositol 3-kinase (p85) is recruited from cytosol to IM, the greater part of which can be accounted for by binding to IRS-1 present in the IM. The p85 binding and phosphatidylinositol 3-kinase activity associated with IRS-2 rapidly decrease in both IM and cytosol, whereas those associated with IRS-1 stay at a relatively high level in IM and increase with time in cytosol despite a return of p85 to the cytosol and decreasing tyrosine phosphorylation of cytosolic IRS-1. These data indicate that IRS-1 and IRS-2 are differentially distributed in the cell and move from IM to cytosol following insulin stimulation. Insulin-stimulated IRS-1 and IRS-2 signaling occurs mainly in the IM and shows different kinetics; IRS-1-mediated signaling is more stable, whereas IRS-2-mediated signaling is more transient. These differences in substrate utilization and compartmentalization may contribute to the complexity and diversity of the insulin signaling network.

3T3 Cells↗
PubMed1998

Simultaneous dorsal dislocation of the metacarpophalangeal and carpometacarpal joints of a finger.

A case of simultaneous dorsal dislocation of the metacarpophalangeal (MP) and carpometacarpal (CMC) joints in the little finger is presented. The patient required a second surgical intervention for volar subluxation of the MP joint which occurred while wearing a dorsal splint following open reduction of the MP joint and closed reduction of the CMC joint. Two years postoperatively, the patient was asymptomatic but was left with mild stiffness of the MP joint.

Adult↗
PubMed1998

Complications in wrap-around-flap donor sites after reconstruction using an arterialized venous flap.

The authors have previously reported on the use of the arterialized venous flap to cover skin defects of the big toe resulting from wrap-around-flap transfers. Nineteen patients who had undergone this procedure were reviewed, to determine the incidence of donor-site complications. Problems identified included delayed wound healing, skin erosion, painful callosity, paresthesia, cold intolerance, and cosmetic appearance However, the functional deficit was not great, and most patients were not troubled by their symptoms. The cosmetic appearance of the donor foot was acceptable in most of the patients.

Adolescent↗
PubMed1998

Recurrent dislocation of the extensor carpi ulnaris tendon.

Five patients with recurrent dislocation of the extensor carpi ulnaris (ECU) tendon resulting from an athletic injury were treated by reconstruction of the ECU tendon sheath, and each had a satisfactory result. Two types of disruption of the fibro-osseous sheath were found. In two cases in which the fibro-osseous sheath ruptured radially, the torn sheath lay on its ulnar groove beneath the ECU tendon. These patients were treated by direct suture of the sheath over the ECU tendon. In three cases in which the fibro-osseous sheath ruptured ulnarly, the torn sheath lay superficial to the ECU tendon. These patients were treated by reconstruction of the sheath using a piece of the extensor retinaculum. We believe that surgical reconstruction of the fibro-oseous sheath of the ECU tendon should be considered for symptomatic dislocation of the ECU tendon, even in an acute case.

Adult↗
PubMed1998

Clinical manifestations due to a point mutation of the mitochondrial tRNAleu(UUR) gene in five families with diabetes mellitus.

It has been shown that an adenine (A) to guanine (G) transition at position 3243 of the mitochondrial transfer RNA(tRNA)leu(UUR) gene is associated with a subgroup of diabetes mellitus. Therefore, we screened for this transition in 86 patients with non-insulin-dependent diabetes mellitus (NIDDM) in which two or three generations were affected with diabetes, in 14 patients with insulin-dependent diabetes mellitus, and in 9 families with diabetes mellitus and/or associated disorders suggesting mitochondrial gene abnormalities. We failed to identify the mutation in 100 diabetic patients, 86 NIDDM and 14 insulin-dependent diabetes mellitus (IDDM). Out of the latter 9 families, we identified an A to G transition in 14 individuals in 5 families. Diabetes mellitus was shown to be maternally inherited in one family. In 9 of 14 patients with the mutation, insulin was required to treat diabetes mellitus, indicating impaired insulin secretion. A hyperglycemic clamp test performed in one subject revealed significant impairment of insulin secretion, whereas euglycemic clamp test showed normal insulin sensitivity in this patient. The heteroplasmy of the mutant mitochondrial DNA (mtDNA) in leukocytes does not appear to correlate with the severity of diabetes in terms of the insulin therapy required. Body mass index of the affected individuals was less than 23.3. In one family, in addition to diabetes mellitus and hearing loss, hypoparathyroidism was associated with the mutation, suggesting that hypoparathyroidism is caused by the impaired processing and/or secretion of proparathyroid hormone due to the mutation. In addition, the affected subjects presented with proteinuria at the time of diagnosis of diabetes mellitus which appeared not to be related with diabetic nephropathy.

Adolescent↗
PubMed1998

Increased adipose expression of the uncoupling protein-3 gene by thiazolidinediones in Wistar fatty rats and in cultured adipocytes.

Uncoupling protein (UCP) 3 and UCP2, mitochondrial carrier proteins dissipating electrochemical gradient across the mitochondrial inner membrane, have been implicated in the regulation of energy metabolism. The UCP3 gene is expressed abundantly in the skeletal muscle, while the UCP2 gene is detected in the white adipose tissue (WAT) with diffuse localization throughout the body. Uncoupling of electron transport and ATP synthesis has been reported to increase glucose uptake, suggesting that UCP may be involved in glucose metabolism. Thiazolidinediones (TZDs), which are insulin-sensitizing agents for NIDDM, have been reported to increase energy expenditure. To elucidate the pathophysiologic significance of UCP3 and UCP2 in the effect of TZDs on glucose metabolism and energy expenditure, we examined their basal mRNA levels in the WAT, brown adipose tissue (BAT), and skeletal muscle from Wistar fatty rats, a rat model of NIDDM and obesity with leptin receptor defect, and investigated expression of the genes encoding UCP3 and UCP2 in Wistar fatty rats and in Wistar lean rats with 2-week oral administration of 3 mg x kg(-1) x day(-1) pioglitazone, a TZD derivative. Basal UCP3 mRNA levels were significantly lower (38 +/- 8, 45 +/- 13, and 76 +/- 6%) in the retroperitoneal WAT, BAT, and skeletal muscle from Wistar fatty rats than in those from Wistar lean rats, while basal UCP2 mRNA levels were significantly higher by 2.1-, 1.8-, and 2.5-fold in the subcutaneous WAT, retroperitoneal WAT, and BAT from Wistar fatty rats, respectively, than in those from Wistar lean rats. In pioglitazone-treated Wistar fatty rats, UCP3 mRNA levels were significantly increased by 2.1-, 2.0-, and 1.6-fold in the epididymal WAT, retroperitoneal WAT, and BAT, respectively, as compared with those in nontreated fatty rats. In pioglitazone-treated lean rats, UCP3 mRNA levels were significantly increased by 1.3-fold in the BAT as compared with those in nontreated lean rats. No significant change of UCP2 mRNA levels was observed in pioglitazone-treated fatty and lean rats. In addition, to examine the direct effect of TZDs on adipocytes, we examined the regulation of UCP3 and UCP2 gene expression using the primary culture of rat mature adipocytes from Sprague-Dawley rats. In rat cultured mature adipocytes, UCP3 mRNA levels were increased in a dose-responsive manner by 10(-5) to 10(-4) mol/l pioglitazone, while there was no significant change of UCP2 mRNA levels. These results clearly demonstrate that UCP3 gene expression is upregulated by TZDs in the WAT and BAT in Wistar fatty rats, an obese model with leptin receptor defect, and that adipose UCP3 gene expression is increased in response to TZDs in vitro. The present study suggests the involvement of UCP3 in the effects of TZDs on energy and glucose metabolism.

Adipocytes↗
PubMed1998

Corrective ulnar osteotomy for malunited anterior Monteggia lesions in children. 12 patients followed for 1-12 years.

We reviewed 12 children, mean 5 (1-12) years, after corrective osteotomy of the ulna, combined with open reduction of the radial head for malunited anterior Monteggia lesions (Bado type I). A simple corrective osteotomy was used in the first 6 patients (group A) and a posterior angular osteotomy was used in the second group of 6 patients (group B). All osteotomies healed uneventfully, but 3 patients had a persistent dislocation of the radial head. Children who had been treated with an angular osteotomy had the best clinical outcome).

Bone Plates↗
PubMed1998

Osteochondritis dissecans of the elbow managed by Herbert screw fixation.

Seven patients (eight elbows) with osteochondritis dissecans were treated with cancellous bone grafts and internal fixation of the fragment using a Herbert screw. Average follow-up was 32 months. All patients were pain-free and returned to previous sporting activities. The postoperative range of motion of the elbow increased by an average of 18 degrees. Radiographs showed complete reossification of the capitular cyst and normally contoured joint surface.

Adolescent↗
PubMed1997

Cloning of rat uncoupling protein-3 and uncoupling protein-2 cDNAs: their gene expression in rats fed high-fat diet.

In order to elucidate energy balance in the skeletal muscle, we cloned cDNA of a homologue of uncoupling protein (UCP) from rat skeletal muscle. We also cloned rat UCP-2 cDNA from rat brown adipose tissue (BAT). The UCP cloned from rat skeletal muscle showed 57% and 72% identity with rat UCP-1 and UCP-2. The mRNA was expressed abundantly in the skeletal muscle, moderately in the BAT, and slightly in the white adipose tissue (WAT) with a major band at 2.5 kb and a minor band at 2.8 kb, while the UCP-2 gene expression was widely detected in the whole body with substantial levels in the WAT and with slight levels in the skeletal muscle and BAT. The rat UCP cloned in the present study showed 86% identity with the recently cloned human UCP-3, which was also expressed abundantly in the skeletal muscle with a signal of 2.4 kb. Therefore, the rat UCP was considered to be rat UCP-3. In rats fed high-fat diet the UCP-3 gene expression was augmented 2-fold in the skeletal muscle while UCP-2 mRNA levels were increased significantly (1.6-fold) in the epididymal WAT. Augmented expression of UCPs may provide defense against high-fat induced obesity and impairment of glucose metabolism.

Adipose Tissue↗