Biomedical subjects

S Hidaka

Publications and source records attributed to S Hidaka.

At least 55 records · Page 3Linked to original sources

PubMed2000

Tissue-specific expression of the uncoupling protein family in streptozotocin-induced diabetic rats.

The vulnerability of streptozotocin (STZ)-induced diabetic rats to cold stress has been established. One of the elements controlling body temperature is thermogenesis, in which uncoupling protein (UCP) is known to play an important role. We have examined UCP2 and UCP3 expressions in brown adipose tissue (BAT), white adipose tissue (WAT), and skeletal muscle (MSL) during the acute and chronic phases of STZ-induced diabetes in rats. The long-term effect and the effect of insulin treatment thereafter were also unexplored previously and are examined in this study. In the acute phase of diabetes (2.5 days after STZ injection), UCP2 gene expression in BAT, WAT, and MSL, and UCP3 expression in the muscle were significantly increased. In the chronic phase of diabetes (21 days after STZ injection), UCP2 and UCP3 expression in the MSL were restored to the control levels without insulin supplementation. UCP2 in BAT and WAT remained high in the chronic phase, whereas UCP3 expression in BAT and WAT, which did not change in the acute phase, was significantly decreased. Insulin supplementation restored UCP2 expression in BAT and WAT, but over-corrected UCP3 in WAT above the control and did not affect UCP3 expression in BAT. Insulin supplementation depressed UCP3 expression in the MSL below control. These results indicate that the effects of STZ-induced diabetes on UCPs gene expression are tissue-specific as well as dependent on the duration of diabetes.

Adipose Tissue↗

PubMed2000

[Syndrome of inappropriate antidiuretic hormone secretion associated with meningeal infiltration of tumor cells and elevated interleukin-1 beta and interleukin-6 in cerebrospinal fluid of a patient with adult T-cell leukemia].

A 73-year-old man with acute adult T-cell leukemia (ATL) in remission was re-admitted to our hospital due to drowsiness, headache, and bilateral knee joint pain on May 17, 1998. On admission, examinations revealed decreased serum sodium concentration (112 mEq/l), low plasma osmotic pressure (259 mOsm/l), and elevated antidiuretic hormone(5.6 pg/ml). Cerebrospinal fluid examination showed an increased number of abnormal flower-like lymphocyte (951/microliter). Brain computed tomography and magnetic resonance imaging found no abnormality in the hypothalamus or pituitary gland. These findings yielded a diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH). Though ATL patients typically exhibit a variety of clinical symptoms, SIADH is rarely one of the complications. Further investigation showed that IL-1 beta and IL-6 concentrations were increased in spinal fluid but not in serum. Recently, it has been reported that exogeneous IL-6 is an inducer of ADH secretion, and that primary ATL cells and HTLV-I infected cell lines can produce IL-6. In this case, we speculated that IL-6 produced by ATL cells that infiltrated a cerebral lesion may have played an important role in the development of SIADH.

Aged↗

PubMed2000

Differences in 20q13.2 copy number between colorectal cancers with and without liver metastasis.

Frequent gains of 20q have been identified recently in many neoplasias, including breast, bladder, ovarian, pancreatic, and colon cancers. A high level of 20q13.2 amplification is associated with poor prognosis in breast cancer. We investigated the copy number of the 20q13.2 region including the ZNF217 oncogene in 17 nonmetastatic colorectal cancers (CRCs), 18 primary CRC tumors with liver metastasis, and 18 metastatic lesions by two-color fluorescence in situ hybridization to evaluate the significance of an increased copy number of 20q13.2 in CRC, especially in those cases with liver metastasis. The frequency of increased relative copy number of the 20q13.2 region was higher in primary and liver metastatic lesions of CRC than in CRC lesions without liver metastasis. In particular, a high-level increase (>3.0-fold) in the relative copy number of 20q13.2 was observed in 2 of 18 (11%) primary CRC lesions with liver metastasis, 7 of 18 (39%) liver metastatic lesions, and in none of the cases of primary CRC without liver metastasis. The absolute and relative copy number of chromosome 20q13.2 was higher in CRCs with metastasis than in CRCs without metastasis. The percentage of cells with high-level 20q13.2 amplification was also higher in both lesions with metastasis per specimen than without metastasis. Our results suggest that the level of 20q13.2 amplification correlates with the metastatic potential and tumor progression of CRC. The results also suggest that 20q13.2 amplification with ZNF217 is associated with increased metastatic potential.

Chromosome Mapping↗

PubMed2000

Cytomegalovirus infection is not necessarily a poor prognostic factor in adult T-cell leukemia/lymphoma.

The relationship between cytomegalovirus (CMV) antigenemia and the clinical course was examined in 57 patients with adult T-cell leukemia/lymphoma (ATLL). All patients included had the acute/lymphoma type of ATL according to the criteria of the Japan Lymphoma Study Group (LSG). CMV antigenemia was assessed on admission and at the time when the patients had fever higher than 37. 5 degrees C, which did not respond to antibiotics for longer than 3 days. The incidence of CMV antigenemia was 44%. Approximately 90% of patients with CMV antigenemia died of infections with viruses, bacteria, and/or fungi, while approximately 40% of patients without CMV antigenemia died of deterioration of ATLL (P<0.0001). In this study, the patients with CMV antigenemia tended to survive longer than those negative for it (321.4 days vs. 266.2 days), although there was no statistical significance (P=0.09). Kaplan-Meier analysis revealed that CMV antigenemia was not a poor prognostic factor. When the disease status of ATLL was evaluated by thymidine kinase (TK) and soluble interleukin 2 receptor (sIL-2R), both had lower titers during CMV antigenemia (TK: P=0.01, sIL-2R: P=0.03, respectively). Therefore, CMV infections in ATLL patients seemed to have bimodal meanings; CMV infection at the end of clinical course were life-threatening, but infection during the first half of clinical course seemed to suppress ATLL activity and to contribute to the longer survival of the patients.

Adult↗

PubMed1999

Alteration of heart uncoupling protein-2 mRNA regulated by sympathetic nerve and triiodothyronine during postnatal period in rats.

To provide tissue-specific and developmental characteristics of gene expression of rat heart uncoupling protein-2 (UCP2), we investigated developmental alterations of UCPs mRNA expression in the heart and brown adipose tissue (BAT), and examined possible up-regulators of heart UCP2 expression using in vitro studies. Heart UCP2 mRNA expression was low during the early postnatal days followed by a rapid and significant increase in the 2nd postnatal week. Heart UCP3 mRNA remained undetectable until the 2nd postnatal week when the expression reached a small but significant peak. BAT UCP1 mRNA was abundantly expressed in the neonate, but the expression rapidly decreased to the adult level. The studies using cultured cardiomyocytes demonstrated that both 10(-8) M triiodothyronine and 10(-7) M isoproterenol, but not phenylephrine, increased UCP2 mRNA expression. These results indicate that the sympathetic nervous system and/or thyroid hormones may be involved in the up-regulation of heart UCP2 gene expression during postnatal development. The increase in postnatal heart UCP2 may provide a key link between the postnatal energy shift and adaptation of rat pups to their novel environment.

Adipose Tissue, Brown↗

PubMed1999

Tumor necrosis factor-alpha regulates in vivo expression of the rat UCP family differentially.

A family of uncoupling proteins (UCPs), free fatty acid anion transporters, plays a crucial role in energy homeostatic thermoregulation. Tumor necrosis factor-alpha (TNF-alpha), a member of the cytokine family, is well known as an endogenous pyrogen. To evaluate the interaction of TNF-alpha with UCPs in thermogenesis, effects of TNF-alpha on rat UCP gene expression were examined in intrascapular brown adipose tissue (BAT), epididymal white adipose tissue (WAT) and soleus muscle (Muscle). Administration of TNF-alpha elevated rectal temperature by 0.7 degree C as well as serum leptin which peaked at 6 h, compared with saline controls. BAT UCP1 mRNA expression was increased by 1.2-fold at 6 h after the TNF-alpha treatment and decreased by 0.8-fold at 16 h after the treatment. In contrast to UCP1 expression in BAT, UCP2 mRNA expressions in BAT, WAT, and Muscle was increased to reach maximum levels of 1.3-, 1.6- and 1.8-fold, respectively, at 16 h after the treatment. UCP3 mRNA in Muscle, but not in BAT or WAT, was exclusively up-regulated by 1.7-fold at 16 h after the treatment. These results indicate that TNF-alpha up-regulates UCP gene expression differentially and tissue dependently, and add novel insights into thermogenesis under conditions of malignancy and inflammation.

Adipose Tissue↗

PubMed1999

Spontaneous regression associated with apoptosis in a patient with acute-type adult T-cell leukemia.

We describe a 76-year-old man with acute-type adult T-cell leukemia, who demonstrated a spontaneous decrease in leukemic cell number, apparently coincident with apoptotic cell death. On admission the patient's white blood cell count was 38.9 x 10(9)/l with 77% abnormal lymphocytes. He also had hypoproteinemia (4.3 g/dl) from protein losing enteropathy. After admission the leukemic cell count decreased without chemotherapy, reaching 5.9 x 10(9)/l after 2 months. Studies of peripheral lymphocytes demonstrated appearance of the apoptotic cells and DNA ladder formation from the beginning of regression. Same truncated proviral DNA was recognized in primary ATL cells through the whole clinical course. The hypoproteinemia improved with intravenous nutrition, followed by increase of the leukemic cells. This case is the first report that demonstrates tumor-cell apoptosis induced clinical regression in adult T-cell leukemia. Further, we speculate that the hypoproteinemia may have been involved in the leukemic cell apoptosis.

Aged↗

PubMed1999

A Japanese herbal medicine, Chujo-to, has a beneficial effect on osteoporosis in rats.

The inhibitory effects of a Japanese herbal medicine, Chujo-to, on the progress of bone loss induced by ovariectomy in rats were investigated. Ovariectomized rats were administered with Chujo-to during weeks 7-14 after ovariectomy. At 14 weeks, the bone mineral density of the tibia from ovariectomized (OVX) rats had decreased by 27% compared with those in the sham-operated rats, and by a 18%-21% and 16% decrease after the administration of Chujo-to and 17 beta-oestradiol, respectively. The surface of a trabecular bone of the tibia in ovariectomized rats had a porous and fibrous appearance, while that of the same bone in sham-operated rats was composed of fine particles. After the administration of Chujo-to or 17 beta-oestradiol, the surface of trabecular bone maintained the porous and fibrous appearance. The uterine weight was not restored by Chujo-to but by 17 beta-oestradiol. These results suggest that Chujo-to has an efficacy on the osteoporosis of rats similar to 17 beta-oestradiol, but with a different mechanism.

Animals↗

PubMed1999

Alteration of p16 (CDKN2) gene is associated with interleukin-2-induced tumor cell growth in adult T-cell leukemia.

Because tumorigenesis frequently involves the dysfunction of cell cycle-related proteins, we examined the effect of mutations in CDK inhibitor p16 and its linked genomic loci p15, cl.B, and 1063.7 on the growth of primary adult T-cell leukemia (ATL) cells. Southern blot analysis of primary ATL cells showed a significantly higher incidence of p16 gene alteration in acute ATL than in chronic ATL [67.7% (23/34) vs. 26.1% (6/23), respectively; p<0.003]. Similarly, polymerase chain reaction (PCR) analysis of p16 exon 2 revealed a higher incidence of alteration in acute ATL than in chronic ATL [52.9% (18/34) vs. 26.1% (6/23), respectively; p<0.05]. PCR-single strand conformation polymorphism analysis of exons 1 and 2 of p16 showed no mutations in the patients, with normal pattern by Southern blotting or PCR analysis. Notably five of six chronic ATL patients with abnormal p16 genes progressed to acute crisis within 4 months. PCR analysis of the p16 linked loci 1063.7, p15 exon 2, and cl.B found homozygous deletion in 55.9%, 20.6%, and 2.9% of acute ATL cells and 39.1%, 13.0%, and 0% of chronic ATL cells, respectively, showing no relationship of homozygous deletion in either loci with disease subtypes. In most cases, deletions were seen in multiple genes, including p16. Acute ATL cells had a higher frequency of multigene deletions than chronic ATL cells [44.1% vs. 17.4%; p<0.05]. When leukemic cells were analyzed for interleukin 2 (IL-2) responsive growth, only p16 gene alteration was directly associated with leukemic cell growth activity. Among leukemic cells showing high IL-2 responsiveness, 73.1% (19/26) had p16 gene alteration vs. 27.8% (5/18) of leukemic cells that showed low IL-2 responsiveness (p<0.005). p16 gene alteration was found in 73.3% (14/19) of leukemic cells showing high autonomous growth rates but in only 40.0% (10/25) of those leukemic cells showing low autonomous growth (p<0.03). These results suggest the following: alteration of p16-related genomic regions in ATL is usually a wide rearrangement including the p16 gene; within this region, only p16 gene alteration is associated with disease aggressiveness; and p16 gene deletion may be a proximate event in leukemogenesis.

Blotting, Southern↗

PubMed1999

NF-kappaB involvement in the activation of primary adult T-cell leukemia cells and its clinical implications.

The HTLV-I provirus-encoded Tax protein induces NF-kappaB in Tax-transfected Jurkat T cells or HTLVL-I- infected T cells in vitro. Tax induction of NF-kappaB is presumed to be involved in proliferation and activation of primary leukemia cells in vivo. Recent studies have demonstrated that NF-kappaB activities in human T cells are mediated by at least four c-Rel-related DNA binding proteins - p50, p55, p75 and p85. We examined the significance of NF-kappaB induction in primary adult T cell leukemia cells and the induction kinetics of each of the four NF-kappaB species. Marked NF-kappaB activity was detected using an electrophoretic mobility shift assay (EMSA) in the primary cells of patients with acute disease, but little activity was noted in the cells of chronic patients. NF-kappaB activity was enhanced in a time-dependent manner in acute type cells cultured with mitogen-free medium; there was no induction of activity in chronic type cells. UV crosslinking demonstrated all four species of NFkappaB complex - high levels of p50 and lower levels of p55 and p75, in acute type cells; chronic type cells showed only the p50. As a control, normal resting T cells similarly showed only p50; control cells showed little change in activity when cultured without mitogenic stimulation, analogous to chronic type ATL. Northern blotting revealed enhancement of c-rel (encoding p85) and KBFI (encoding p50 and p55) expression in acute type cells during culture, while there was no significant enhancement of mRNAs in chronic type ATL cells or unstimulated normal T cells. Northern blotting also revealed that Tax is upregulated at the mRNA level in acute- but not chronic-type cells during culture. Expression of c-rel and KBF1 mRNAs in acute type cells appeared to be related to Tax mRNA expression. These results suggest that Tax is capable of inducing nuclear expression of all four NF-kappaB species in primary ATL cells of acute type patients, with marked effects on p55, p75, and p85. Tax induction of NF-kappaB species is regulated, at least in part, at a pretranslational level involving increases in c-rel and KBF1 mRNA.

Acute Disease↗

PubMed1999

Induction of rat uncoupling protein-2 gene treated with tumour necrosis factor alpha in vivo.

BACKGROUND: The cytokine tumour necrosis factor (TNF) alpha has been reported to induce metabolic abnormalities such as anorexia and thermogenesis. To investigate functional modulators of uncoupling protein-2 (UCP2) gene expression, we examined the effects of TNF-alpha on UCP2 mRNA expression in rats. METHODS: Mature male Wistar King A (WKA) rats at 10-11 weeks of age were treated with recombinant human TNF-alpha at a dose of 0.6 nmol 100 g-1 body weight by intraperitoneal administration. RESULTS: TNF-alpha treatment induced an increase in UCP2 mRNA expression in broadly distributed tissues including brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle, and an elevation of ob gene mRNA expression in WAT. After the TNF-alpha treatment, an increase in plasma leptin concentration occurred in an ob gene-dependent manner, accompanied by an anorectic effect. CONCLUSION: The present results provide evidence for a new regulatory loop involving TNF-alpha and UCP2, and add novel insights into the regulatory mechanisms of energy homeostasis.

Adipose Tissue↗

PubMed1999

Subthalamic nucleus lesions induce deficits as well as benefits in the hemiparkinsonian rat.

Lesions of the subthalamic nucleus can restore some imbalances in motor output of the basal ganglia induced by nigrostriatal dopamine depletion, and have been proposed as a potential therapy for Parkinson's disease. Although there is substantial supporting evidence from experimental studies in both rats and primates, there is less information on the effects of subthalamic lesions alone. In order to characterize potential side effects, the present study evaluates the behavioural effects of unilateral excitotoxic lesions of the subthalamic nucleus in rats that have previously received either unilateral saline or 6-hydroxydopamine injections into the nigrostriatal bundle on the same side. The 6-hydroxydopamine lesions induced ipsilateral orientation asymmetries in head position and body axis bias, rotational asymmetries following injections of direct or indirect dopamine agonists, neglect of contralateral stimuli, and a reduction in the numbers of pellets retrieved with the contralateral paw in a skilled reaching task. Subsequent excitotoxic lesions of the subthalamic nucleus reduced (but did not abolish) rotational asymmetries, had no effects on the measures of neglect and skilled paw-reaching, and produced contralateral orientation biases in head turning and body axis curling. Rats that received subthalamic lesions alone exhibited de novo impairments comprising contralateral biases in the orientation tests. These results support a neuromodulatory role of the subthalamic nucleus in regulating motor outputs of the basal ganglia, and caution that there may be distinct side effects of the lesion by itself. Whereas some impairments attributable to dopamine depletion may be alleviated by subthalamic manipulations, other symptoms are not, or may even be aggravated.

Animals↗

PubMed1999

Hypothalamic neuronal histamine as a target of leptin in feeding behavior.

Leptin, an ob gene product, has been shown to suppress food intake by regulating hypothalamic neuromodulators. The present study was designed to examine the involvement of brain histamine in leptin-induced feeding suppression. A bolus infusion of 1.0 microg leptin into the rat third cerebroventricle (i3vt) elevated the turnover rate of hypothalamic neuronal histamine (P < 0.05) as assessed by pargyline-induced accumulation of tele-methylhistamine (t-MH), a major metabolite of histamine. No remarkable change in the mRNA expression of histidine decarboxylase (HDC), a histamine-synthesizing enzyme, was observed in the hypothalamus after i3vt infusion of leptin. These results indicate that leptin increases histamine turnover by affecting the posttranscriptional process of HDC formation or histamine release per se. As expected, concomitant suppression in 24-h cumulative food intake was also observed after infusion of leptin. Systemic depletion of brain histamine levels by pretreatment with an intraperitoneal injection of 224 micromol/kg alpha-fluoromethylhistidine (FMH), a suicide inhibitor of HDC, attenuated the leptin-induced feeding suppression by 50.7% (P < 0.05). This attenuation of feeding suppression was mimicked by the i3vt infusion of 2.24 micromol/kg FMH before leptin treatment (P < 0.05). In addition, concentrations of hypothalamic histamine and t-MH were lowered in diabetic (db/db) mice, which are known to be deficient in leptin receptors (P < 0.05 vs. lean littermates for each amine), although the amine levels were higher in diet-induced obese rats (P < 0.05 for each amine). Leptin-deficient obese mice (ob/ob) showed lower histamine turnover (P < 0.05 vs. lean littermates), which recovered after leptin infusion. Thus, a growing body of results points to an important role for the hypothalamic histamine neurons in the central regulation of feeding behavior controlled by leptin.

Animals↗

PubMed1999

Streptozotocin treatment upregulates uncoupling protein 3 expression in the rat heart.

Diabetic rats have a deficiency in their heart ATP concentrations, and although the mechanism remains to be elucidated, this deficiency may involve increased uncoupling of oxidative phosphorylation. To investigate whether heart uncoupling proteins (UCPs) are subject to transcriptional regulation in diabetes, we examined changes in UCP mRNA expression in the heart of streptozotocin-induced diabetic (STZ-DM) rats. Heart UCP3 mRNA expression significantly increased by 9.4-fold in STZ-DM rats, while levels of UCP2 mRNA expression were not significantly altered. Insulin supplementation in STZ-DM rats returned UCP3 mRNA concentrations to control levels. The expression of UCP3 mRNA was similarly elevated in the heart of fasted rats, which also have hypoinsulinemia and hyper-free fatty acidemia but, unlike the STZ-DM rats, are hypoglycemic. Since hyperinsulinemia alone was previously reported to not affect UCP3 gene expression in the muscle, these results indicate that hyper-free fatty acidemia is a potent enhancer of UCP3 gene expression in the diabetic rat heart. Interestingly, we found no changes in UCP3 mRNA levels in Zucker fatty (fa/fa) rats with excessive chronic hyper-free fatty acidemia, which suggests that upregulation of heart UCP3 mRNA may depend on an acute change in free fatty acid concentrations rather than on their sustained elevation. High-energy ATP deficiencies in the diabetic rat heart may primarily result from proton leakage due to the upregulation of UCP3 expression.

Animals↗

PubMed1999

Protection against cis-diamminedichloroplatinum-induced nephrotoxicity by 2,3-dimercaptosuccinic acid in rats.

The present study was designed to examine the usefulness of 2,3-dimercaptosuccinic acid (DMSA) for the purpose of reducing cis-diamminedichloroplatinum (DDP)-induced nephrotoxicity and effective clinical use of DDP and safe. The effectiveness of DMSA on the DDP-excretion in rat kidney was observed by measuring the platinum concentration using Atomic Absorption Instrument. Co-administration of DMSA (1.0 or 2.0 mmol/kg) 1 hour after DDP injection (20 mumol/kg) showed more decrease in the platinum concentration than that immediately after DDP injection. The alleviating effect of DMSA on DDP toxicity was evaluated by lipid peroxidation, enzymatic antioxidants, and glutathione levels. The administration of DDP alone caused a significant increase in lipid peroxidation and significant decreases in enzymatic antioxidants and glutathione levels in the kidney. Co-administration of DMSA (2.0 mmol/kg) 1 hour after DDP injection showed the most effective reduction of these enzymatic damages caused by DDP. These findings suggested that the co-administration of DMSA (2.0 mmol/kg) 1 hour after DDP injection leads DDP to effective excrete from renal tissue and suppresses the lipid peroxide reaction and results in reduction of nephrotoxicity.

Animals↗

PubMed1999

Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma.

Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.

Administration, Oral↗

PubMed1998

Do obesity and non-insulin dependent diabetes mellitus aggravate exercise-induced microproteinuria?

We evaluated the role of obesity in proteinuria by treadmill exercising of simple obese subjects and non-obese subjects with non-insulin dependent diabetes mellitus in whom the albumin excretion rate at rest was within normal range. Non-obese healthy volunteers were studied as the controls. The fractional renal clearances of four endogenous proteins, albumin, IgG, IgG4, and beta2-microglobulin were measured before, during, and after treadmill exercise in 17 simple obese and 15 non-obese diabetic subjects, and in 21 normal subjects. Exercise increased the fractional albumin clearance in all groups. In diabetic subjects, the fractional IgG4 clearance also increased: fractional beta2-microglobulin clearance increased in normal controls and in diabetics. In obese subjects, the fractional clearances of albumin, IgG, and IgG4 were similar to those in normal controls, but fractional beta2-microglobulin clearance was significantly lower. These results suggest that enhanced microalbuminuria in obese subjects is probably of glomerular origin. In normal subjects and diabetics, exercise-induced microproteinuria is probably of both glomerular and tubular origin. Defect in the charge-selective barrier of the glomerular capillary wall has been implicated in diabetics. Thus some additional factors relevant to obesity must be taken into account in the consideration of the mechanism of microalbuminuria in diabetics with obesity.

Adolescent↗

PubMed1998

Molecular cloning of rat uncoupling protein 2 cDNA and its expression in genetically obese Zucker fatty (fa/fa) rats.

We isolated rat UCP2 cDNA, which has been proposed to play an important role in mammalian thermogenesis and body weight regulation. The nucleotide sequence of the cDNA revealed that the rat UCP2 protein is composed of 309 amino acid residues, and is 99% and 95% identical to the mouse and human proteins, respectively. The molecular weight of rat UCP2, calculated from the predicted amino acid sequence, was 33,369, and the UCP2 protein of this size was detected when the cDNA was expressed in vitro. Northern blot analysis revealed that the corresponding mRNA is approximately 1.7 kb in size, and is expressed in a variety of rat organs, with predominant expression in the heart, lung and spleen. UCP2 mRNA levels in the heart, liver, muscle and epididymal adipose tissue of Zucker fatty (fa/fa) rats were comparable to those in the lean littermates, while ob mRNA level markedly increased in the epididymal adipose tissue of Zucker (fa/fa) rats.

Amino Acid Sequence↗