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ABSTRACT: Postprandial hyperglycemia and hyperlipidemia are frequently associated with type 2 diabetes mellitus. The aim of the present study is to investigate the clinical determinants of postprandial glycemia and lipemia, especially serum high-molecular weight adiponectin.
Twenty-seven diabetic patients treated with diet alone and 13 healthy volunteers took liquid test meal containing 53 g carbohydrate and 47 g lipid, dosed with nonradioactive isotope (13)C-acetate. Venous blood and breath samples were obtained for 180 min after the meal. Gastric emptying was evaluated by peak excretion time of (13)CO(2) in the breath samples. Delayed gastric emptying was defined as peak excretion time > 2.5 h (mean + 2 SD in the healthy volunteers).
Diabetic patients showed delayed insulin secretion, postprandial hyperglycemia and hyperlipidemia compared with control. Postprandial glycemic increases significantly correlated with enhanced gastric emptying. Serum high-molecular weight adiponectin correlated with postprandial glycemic increases at 30 and 60 min after meal (r = 0.42, p < 0.05; r = 0.37, p < 0.05, respectively). Serum high-molecular weight adiponectin also correlated with gastric emptying (versus peak excretion time r = - 0.58, p < 0.05). In addition, diabetic patients with delayed gastric emptying showed the suppressed postprandial glycemia with lower serum high-molecular weight adiponectin than those with normal gastric emptying. On the other hand, postprandial increases in serum triglyceride were not related to serum high-molecular weight adiponectin or gastric emptying, but significantly related to liver function test (serum transaminases) and body mass index.
Early postprandial glycemic increases were related to elevated serum high-molecular weight adiponectin, which might be associated with enhanced gastric emptying.
Diabetes/Metabolism Research and Reviews 04/2009; 25(4):344-50. · 3.37 Impact Factor
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ABSTRACT: Although skin oxygenation is an important factor in the development and healing of foot ulcers, its regulation was not fully understood. We studied changes in foot skin oxygenation and blood flow during postural changes in patients with type 2 diabetes mellitus.
Skin oxygenation was measured using transcutaneous oxygen pressure (TcPO(2)) and skin blood flow by laser Doppler flowmetry in 40 patients with type 2 diabetes mellitus without evidence of peripheral arterial disease and 13 healthy control subjects.
TcPO(2) in the supine position was significantly lower in patients with type 2 diabetes mellitus compared with control, although skin blood flow was not different. In the sitting position, TcPO(2) significantly increased in control and diabetic patients. The postural change-related increase in TcPO(2) was significantly enhanced in diabetic patients. On the other hand, skin blood blow significantly decreased in the sitting position from the supine position in control subjects but remained stable in diabetic patients. Orthostatic drop in systolic blood pressure correlated negatively with TcPO(2) in the supine position while correlated positively with %change in TcPO(2) and blood flow by postural changes.
The present study demonstrated the dissociated regulation of skin oxygenation and blood flow in response to leg dependency. Impaired postural vasoconstriction was associated with altered regulation of skin oxygenation probably due to sympathetic vascular dysfunction in diabetic patients.
Experimental and Clinical Endocrinology & Diabetes 08/2007; 115(7):444-7. · 1.69 Impact Factor
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ABSTRACT: Increased oxidative stress may contribute to the development of diabetic nephropathy. Conversely, it has been proposed that enhanced glomerular production of prostaglandin E(2) (PGE(2)) may be the cause of glomerular hyperfiltration in streptozotocin (STZ)-induced diabetic rats. As the role of superoxide anion (O(2-)) production in early diabetic nephropathy is not fully understood, we investigated the effect of vitamin C and desferrioxamine treatment on glomerular O(2-) and PGE(2) production in diabetic rats.
STZ-induced diabetic rats were given drinking water containing 1 g/l of vitamin C and desferrioxamine for 10 days, and glomerular O(2-) production, glomerular PGE(2) synthesis and creatinine clearance were examined.
Glomerular O(2-) production increased in untreated diabetic rats compared to non-diabetic controls (142.2 +/- 12.4 vs. 65.4 +/- 3.6 counts/mg protein/min). Treatment with vitamin C and desferrioxamine significantly decreased glomerular O(2-) production (93.7 +/- 6.7 counts/mg protein/min). Glomerular PGE(2) synthesis and creatinine clearance were significantly increased in untreated diabetic rats compared to controls and PGE(2) synthesis was reduced and creatinine clearance tended to decrease by the treatment.
Our results demonstrated that vitamin C and desferrioxamine suppressed the enhanced glomerular O(2-) production with subsequent decrease in PGE(2) production. Antioxidant therapy may be beneficial in preventing the development of diabetic nephropathy.
Diabetes Obesity and Metabolism 02/2005; 7(1):106-9. · 3.38 Impact Factor
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ABSTRACT: To elucidate the relationship between glycaemic control, blood pressure and body-weight change after smoking cessation in type 2 diabetic patients.
We examined HbA(1c), blood pressure and body weight in 15 type 2 diabetic patients before, 6 and 12 months after quitting smoking. Sixteen type 2 diabetic patients who did not quit smoking served as control.
Body weight slightly increased after quitting smoking. Although HbA(1c) levels showed no change in the control group, those in patients who quit smoking significantly increased (6.8 +/- 0.3% before quitting smoking; 7.4 +/- 0.3% 6 months after quitting smoking, p < 0.05; 7.8 +/- 0.4% 12 months after quitting smoking, p < 0.001). Fasting blood glucose also increased in patients who quit smoking. The increase in body weight after quitting smoking did not correlate with the deterioration of glycaemic control. Diastolic blood pressure showed no change in control, whereas that in patients who quit smoking increased at month 12 (69 +/- 3 vs. 76 +/- 3 mmHg, p < 0.01). The increase in HbA(1c) at month 12 after quitting smoking correlated with body mass index before quitting smoking (r = 0.72, p < 0.005) and serum triglyceride before quitting smoking (r = 0.68, p < 0.01).
Glycaemic control and diastolic blood pressure deteriorated in type 2 diabetic patients after quitting smoking. Type 2 diabetic patients who want to stop smoking need a caution to prevent deterioration of glycaemic control and blood pressure after quitting smoking.
Diabetes Obesity and Metabolism 05/2004; 6(3):181-6. · 3.38 Impact Factor
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ABSTRACT: Urocortin is a newly identified member of the corticotropin-releasing factor (CRF) neuropeptide family, and is known to be involved in the modulation of the inflammatory process. We examined the expression of urocortin, CRF and their receptors (CRF receptor; CRF-R) in the synovial tissue of patients with rheumatoid arthritis (RA) in order to study the possible biological roles of urocortin. Synovial tissues/fluids were obtained from 38 patients with RA, nine patients with osteoarthritis and four with trauma. We studied the concentration of urocortin in the synovial fluid using RIA, and the expression of urocortin in synovial tissue using immunohistochemistry, mRNA in situ hybridization and reverse transcriptase-PCR (RT-PCR). In addition, we examined the immunolocalization of CRF and the expression of CRF-R1, -R2-alpha and -R2-beta mRNAs utilizing RT-PCR in these synovial tissues. Urocortin concentrations in synovial fluid were higher in RA patients (79.8+/-154 pg/ml) than in control patients (12.3+/-4.8 pg/ml; P< or =0.05). Urocortin immunoreactivity and mRNA signals were both detected in synovial cells, lymphocytes, fibroblasts and macrophages. The number of urocortin-positive cells in the synovium was significantly higher in RA (73.1+/-32.1 cells per high-power field) than in control (18.4+/-10.4 cells per high-power field) patients. In addition, both urocortin immunoreactivity and mRNA signals in the synovium reached maximum levels in the active stage of RA inflammation. Moreover, the number of immunoreactive urocortin-positive cells was significantly correlated with the urocortin concentration in synovial fluid (r=0.705; P<0.001) and with histologically defined local inflammatory activity (r=0.641; P<0.001). The distribution and number of immunoreactive CRF-positive cells in synovial tissue were similar to those of urocortin-positive cells (r=0.701; P<0.001). Urocortin, CRF-R1 and CRF-R2-alpha mRNAs detected by RT-PCR were expressed in in the synovium of 10/10, 10/10 and 2/10 RA patients respectively, but CRF-R2-beta was not expressed. Urocortin was actively synthesized in the synovium of RA patients. The present study suggests that urocortin may play an important role as an autocrine and/or paracrine regulator of synovial inflammation in RA.
Clinical Science 07/2001; 100(6):577-89. · 4.61 Impact Factor
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Diabetes Care 04/2001; 24(3):603-4. · 8.09 Impact Factor
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Y Muramatsu,
K Fukushima, K Iino,
K Totsune,
K Takahashi,
T Suzuki,
G Hirasawa,
J Takeyama,
M Ito,
M Nose,
A Tashiro,
M Hongo,
Y Oki,
H Nagura,
H Sasano
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ABSTRACT: Urocortin is a newly identified member of the CRF neuropeptide family. Urocortin has been found to bind with high affinity to CRF receptors. The present study investigated urocortin and CRF receptor expression in human colonic mucosa. Non-pathologic sections of adult colorectal tissues were obtained from patients with colorectal cancer at surgery. Urocortin expression was examined using immunohistochemistry and messenger (m) RNA in situ hybridization. Isolated lamina propria mononuclear cells (LPMC) and epithelial cells were also analyzed by flow cytometry for the characterization of urocortin-positive cells, and by RT-PCR for detection of urocortin, CRF, and CRF receptor mRNA. Urocortin peptide distribution at various stages of human development (n = 35, from 11 weeks of gestation to 6 years of age) was examined by immunohistochemistry using surgical and autopsy specimens. Immunoreactive urocortin and urocortin mRNA were predominantly detected in lamina propria macrophages. Urocortin peptide expression was detected from as early as three months of age, but not before birth or in neonates. Urocortin, CRF receptor type 1 and type 2 alpha mRNA were detected in LPMC. CRF receptor type 2 beta mRNA, a minor isoform in human tissues, was also detected in LPMC, but at lower levels. Urocortin is locally synthesized in lamina propria macrophages and may act on lamina propria inflammatory cells as an autocrine/paracrine regulator of the mucosal immune system. The appearance of urocortin after birth indicates that the exposure to dietary intake and/or luminal bacteria after birth may contribute to the initiation of urocortin expression in human gastrointestinal tract mucosa.
Peptides 01/2001; 21(12):1799-809. · 2.43 Impact Factor
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ABSTRACT: We compared the effects of hypothalamic obesity induced by neonatal monosodium glutamate (MSG) treatment between spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Newborn WKY and SHR were injected intraperitoneally with 4 mg/kg body weight of MSG daily for 5 days. At 6 months of age, the obesity of SHR was more advanced than that of WKY, but at 14 months of age the severity of obesity was similar between the two strains. Hypertriglyceridemia was enhanced in MSG-treated SHR as compared with MSG-treated WKY. Systolic blood pressure measured by the tail-cuff method was consistently lower in MSG-treated SHR than in control SHR, whereas blood pressure was not affected by neonatal MSG treatment in WKY. Food restriction reduced body weight more in control SHR than in control WKY, with the former also showing enhanced ketogenesis. Neonatal MSG treatment abolished the accelerated reduction of body weight in SHR. Serum leptin concentration was markedly increased in MSG-treated obese rats, though no differences were seen between WKY and SHR in the control or MSG-treated groups. Serum leptin was closely correlated with both Lee obese index and mesenteric fat weight over the strain. Blood flow in interscapular brown adipose tissue (BAT) measured by Laser Doppler flowmetry was significantly increased in response to beta3-adrenoceptor agonist BRL26830A in both the control and MSG-treated rats. However, the response of blood flow was not affected by MSG treatment or strain difference. The present study demonstrated some strain differences in response to neonatal MSG treatment between WKY and SHR. These differences could not be explained by the difference in serum leptin level or beta3-adrenergic reactivity in BAT.
Hypertension Research 10/2000; 23(5):503-10. · 2.58 Impact Factor
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ABSTRACT: Laparoscopic adrenalectomy has become increasingly popular because of its minimally invasive nature, but guidelines for selection of cases suitable for this surgical procedure have not been established. We report a 52-year-old woman with adrenocortical carcinoma, manifesting as Cushing's syndrome, treated with laparoscopic adrenalectomy. The tumour was removed in toto and had been histologically diagnosed as adrenocortical adenoma. However, the patient developed intra-abdominal peritoneal dissemination of carcinoma 15 months after surgery. Review of the histopathological findings of the resected adrenocortical tumour revealed that the neoplasm met five out of nine histological criteria for adrenocortical malignancy, and was diagnosed as adrenocortical carcinoma. Histopathological examination of the tumour was also consistent with adrenocortical carcinoma. The patient responded extremely well to chemotherapy, including carboplatin, etoposide and o,p'-DDD (1,1-dichlorodiphenyldichloroethane), and a subsequent CT (computed tomography) scan 12 months after the start of chemotherapy demonstrated no evidence of disease. However, the patient developed neurological impairment, including dysarthria, as a side-effect of o, p'-DDD. The patient died of aspiration pneumonia due to a decreased pharyngeal reflex. Postmortem examination revealed no foci of residual carcinoma. This case report emphasizes the importance of excluing possible adrenocortical malignancy in patients considered for laparoscopic adrenalectomy, histopathological diagnosis of adrenocortical malignancy and careful monitoring for neurotoxicity during o,p'-DDD treatment.
Clinical Endocrinology 09/2000; 53(2):243-8. · 3.17 Impact Factor
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ABSTRACT: Thiazolidinediones, synthetic ligands of peroxisome proliferator-activated receptor gamma (PPARgamma), are reported to have direct beneficial effects on diabetic nephropathy without lowering blood glucose levels in human and rat. We hypothesized these effects of thiazolidinediones might be derived from PPARgamma activation of kidney cells, and we examined the expression of PPARgamma and the effect of PPARgamma agonists, troglitazone and 15-deoxy-delta-prostaglandin J2 (15d-PGJ2), on the proliferation and differentiation in rat mesangial cells. A single band of mRNA of PPARgamma with a predicted size was detected in reverse transcription-polymerase chain reaction products (RT-PCR) using established PCR probes of PPARgamma. PPARgamma protein in rat mesangial cells was identified as PPARgamma1 by a Western blot. In a gel mobility shift assay to determine a binding activity of PPARgamma, the nuclear protein from rat mesangial cells bound to a (32)P-labeled oligonucleotide probe, including PPAR response elements. A synthetic and a natural ligand of PPARgamma, troglitazone and 15d-PGJ2, decreased thymidine incorporation in a dose dependent manner. After 7 days incubation with troglitazone and 15d-PGJ2, alpha-smooth muscle actin expression, a marker of mesangial cell de-differentiation, was decreased significantly compared to that of control. These results indicate that PPARgamma1 is expressing in rat mesangial cells, and PPARgamma1 activation with its agonists modulates the proliferation and differentiation of cultured rat mesangial cells.
Biochimica et Biophysica Acta 07/2000; 1497(1):148-54. · 4.66 Impact Factor
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ABSTRACT: The pathophysiology of brain damage induced by severe hypoglycemia is still unknown. We experienced a case with type 1 diabetes and recurrent severe hypoglycemic coma who showed a central brain atrophy and an abnormal cerebrospinal fluid flow, suggesting normal pressure hydrocephalus. Following this case, the CSF flow was studied using 111In-DTPA cisternography in six consecutive diabetic patients admitted for repeated episodes of hypoglycemic coma. All the patients showed the central brain atrophy on computed tomography and four of them (67%) had the ventricular reflux, with delayed clearance of 111In-DTPA. Two patients with abnormal CSF flow showed cognitive dysfunction by WAIS or WAIS-R. In contrast, none of five randomly selected diabetic patients, without hypoglycemic coma showed abnormal CSF flow. Our results suggest the presence of normal pressure hydrocephalus in diabetic patients with recurrent hypoglycemic coma. It may associate with the cognitive dysfunction.
Diabetes Research and Clinical Practice 03/2000; 47(2):105-10. · 2.75 Impact Factor
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ABSTRACT: We previously reported that sodium-dependent glucose uptake is present in bovine retinal pericytes and that phlorizin normalizes its glucose consumption under high glucose conditions. To clarify the effect of phlorizin on morphological and functional change of retinal pericytes under high glucose conditions, retinal pericytes were incubated in media with 5 mM glucose, 30 mM glucose, and 30 mM glucose plus 0.2 mM phlorizin for 7 days. The diameter of cells in the concentrations of glucose more than 10 mM were significantly larger than those in 5 mM glucose and 30 mM glucose plus phlorizin. Glucose, sorbitol and fructose contents of the cells in 30 mM glucose were significantly increased compared with those in 5 mM glucose, and were normalized by phlorizin. Thymidine uptake in the concentrations of glucose more than 20 mM was significantly decreased compared with that in 5 mM glucose. Myoinositol uptake, and DNA in 30 mM glucose were significantly reduced, and were normalized with phlorizin. Myoinositol content in 30 mM glucose was the same as that in 5 mM glucose, but was significantly decreased by phlorizin. The ratios of glucose to sorbitol or fructose in 30 mM glucose were significantly decreased, compared with those in 5 mM glucose and 30 mM glucose plus phlorizin. Therefore, the cellular enlargement and decreased DNA synthesis in cultured bovine retinal pericytes with abnormal glucose metabolism under high glucose conditions are attenuated by phlorizin, independent of the cellular myoinositol content.
Biochimica et Biophysica Acta 02/1999; 1453(1):83-91. · 4.66 Impact Factor
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ABSTRACT: Plasma immunoreactive (IR-) urocortin (Ucn) and corticotropin-releasing factor (CRF) levels in pregnant women were measured by their specific radioimmunoassays after extraction. Although plasma IR-CRF levels were increased in pregnant women as compared to men and non-pregnant women, there was no difference of plasma IR-Ucn levels among groups. Ucn mRNA was detected in cytotrophoblasts and syncytiotrophoblasts by in situ hybridization. A reverse-phase high-performance liquid chromatography (HPLC) showed the major peak of IR-Ucn in placenta and plasma that had similar chromatographic mobility to synthetic Ucn1-40. These data suggest that Ucn is produced and processed into the same form of synthetic Ucn in placenta, but not secreted into maternal blood.
Peptides 02/1999; 20(2):205-9. · 2.43 Impact Factor
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K Iino,
H Sasano,
Y Oki,
N Andoh,
R W Shin,
T Kitamoto,
K Takahashi,
H Suzuki,
F Tezuka,
T Yoshimi,
H Nagura
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ABSTRACT: Urocortin is a recently identified neuropeptide of the corticotrophin-releasing factor (CRF) family in the mammalian brain and has been demonstrated to stimulate ACTH secretion from pituitary cells, but its expression in human brain tissue including the hypothalamus has not been examined. In this study, we first examined urocortin expression in the hypothalamus (20 cases) and pituitary stalks (17 cases) of human brain obtained from autopsy using immunohistochemistry and mRNA in situ hybridization.
Neither urocortin immunoreactivity nor mRNA hybridization signals were detected in the hypothalami and pituitary stalks while CRF immunoreactivity was detected in the paraventricular nuclei of the hypothalami in 10/20 cases and in nerve fibres of the stalks in 17/17 cases. These results indicate that urocortin does not act on the hypothalamo-pituitary-adrenal axis, at least not in the same manner as CRF in humans. We then examined urocortin expression in various portions of the brain in 7 cases. Both urocortin immunoreactivity and mRNA hybridization were detected in Purkinje cells of the cerebellum and anterior horn cells of the spinal cord in specimens examined. Urocortin expression was, however, variably seen in superior olivary nuclei (two out of six cases examined) and in the Edingar-Westphal nuclei (one out of three cases examined).
The distribution of urocortin in the human central nervous system suggests that urocortin may work as a neurotransmitter like other neuropeptides in the human.
Clinical Endocrinology 02/1999; 50(1):107-14. · 3.17 Impact Factor
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ABSTRACT: To elucidate the contribution of diabetic state toward the accumulation of lysophosphatidylcholine (LPC) in low density lipoprotein (LDL), the LPC molecular species in LDL and high density lipoprotein (HDL) obtained from alloxan-induced diabetic rats were determined by high performance liquid chromatography. The palmitoyl LPC (PLPC) per protein was increased in the LDL of diabetic rats (p < 0.05), whereas the stearoyl LPC (SLPC) decreased in both the LDL and HDL of diabetic rats (p < 0.001) in comparison to nondiabetic rats. After the dietary administration of probucol for 4 weeks, the concentrations of SLPC and PLPC in the LDL of diabetic rats and of SLPC in the LDL of nondiabetic rats all significantly decreased by probucol (all; p < 0.01), with a concomitant decrease of the plasma concentrations of total and HDL cholesterol, and phospholipid, compared with those without probucol. The level of TBARS per protein in LDL increased in diabetic rats, and decreased by probucol (p < 0.01). In conclusion, the oxidative stress is thought to be an important factor to accumulate LPC in LDL, although the paradoxical decrease of SLPC in diabetic LDL suggests a non-oxidative metabolism with a preference for the LPC molecular species. The reducing effect of probucol on LPC may not be solely attributed to its antioxidative effect.
Experimental and Clinical Endocrinology & Diabetes 01/1999; 107(6):337-42. · 1.69 Impact Factor
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ABSTRACT: Recent immunohistochemical analysis of cell cycle-related proteins such as p27, a cell cycle inhibitory protein, and Ki-67, a proliferation marker, indicated their possible values in predicting the biologic behavior of various human neoplasms. In this study, we performed an immunohistochemical analysis of p27 and Ki-67 in 42 adrenocortical neoplasms (12 adrenocortical carcinomas, 24 adrenocortical adenomas) and 6 normal adrenal glands to evaluate their possible values in diagnosing adrenocortical malignancy and in predicting the biologic behavior of carcinomas. We detected Ki-67 and p27 immunoreactivity in the nuclei of all of our cases, and we observed a significant negative correlation (r = -0.572, P < .001) between the p27 and Ki-67 labeling indexes (LIs). The LIs of p27 and Ki-67 were 61.7+/-2.6 and 0.28+/-0.08 in the normal adrenal cortex and 59.4+/-6.5 and 0.33+/-0.11 in the adenomas, respectively, with no significant differences between the LIs of the adenomas and normal adrenals. The LIs of p27 and Ki-67 in the carcinomas were 48.9+/-7.5 and 630+/-6.21, respectively. The LI of p27 in the carcinomas was significantly lower than that in the adenomas. The LI of Ki-67 in the carcinomas was significantly higher than that in the adenomas (P < .01). Among carcinoma cases, the Ki-67 LI in living cases tended to be lower than that in deceased cases, and the p27 LI in living cases tended to be higher than that in deceased cases, but these differences did not reach statistical significance. These results indicated that decreased p27 protein expression might cause increased cell proliferation in adrenocortical carcinoma cells in combination with other positive and/or negative regulators of the cell cycle. These results also suggested that immunohistochemical analysis of p27 and Ki-67 might be useful in distinguishing between adrenocortical adenoma and carcinoma
Modern Pathology 12/1998; 11(12):1165-70. · 4.79 Impact Factor
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ABSTRACT: In the present study, we examined the direct regulatory effect of rat calcitonin gene-related peptide (CGRP) on adrenocorticotropin (ACTH) release from rat cultured anterior pituitary cells. CGRP significantly increased ACTH release at concentrations of 10(-8)-10(-11) M. The ACTH release was gradually increased by CGRP concentrations lower than 10(-10) M, and was decreased at concentrations higher than 10(-9) M, presenting a bell-shaped dose-response curve. As well as having an additive effect on corticotropin-releasing factor-induced ACTH release, CGRP stimulated the accumulation of intracellular cAMP. The CGRP-induced ACTH release was inhibited by a protein kinase A inhibitor, suggesting that its stimulatory effect on the ACTH release was mediated via an adenylate-cyclase-protein kinase system. CGRP-like immunoreactive nerve fibers have been reported to innervate the anterior pituitary, so that the stimulatory effect of CGRP on the ACTH release suggests that this peptide may be involved in neural regulation of hormone secretion in the anterior pituitary.
Journal of Neuroendocrinology 06/1998; 10(5):325-9. · 3.14 Impact Factor
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ABSTRACT: The present study was designed to develop an animal model of multiple risk factors, including obesity, hypertension, non-insulin-dependent diabetes mellitus, and hyperlipidemia. Hypothalamic obesity was induced by neonatal monosodium glutamate (MSG) treatment in spontaneously hypertensive rats (SHR). Female newborn SHR were treated intraperitoneally with 2 or 4 mg/kg body weight of MSG for 5 days. Obesity developed in SHR treated with 4 mg/kg of MSG but not in SHR treated with 2 mg/kg of MSG. Obese SHR had impaired glucose tolerance, hyperinsulinemia, and hypertriglyceridemia. However, the severity of hypertension was attenuated in obese SHR as compared with control SHR. The degree of obesity was closely related to the metabolic abnormalities, but inversely correlated with the blood pressure level. Macrovascular changes were investigated in obese SHR at 14 months of age. Intimal thickening was accelerated in the carotid artery of obese SHR as compared with that of nonobese SHR. Aortic contents of DNA and total cholesterol were significantly increased in obese SHR. SHR associated with MSG-induced obesity showed major manifestations of metabolic syndrome X. This animal model may be useful to study the clustering of risk factors for the development of macrovascular diseases.
Hypertension Research 04/1998; 21(1):1-6. · 2.58 Impact Factor
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ABSTRACT: Regional distribution of urocortin-like immunoreactivity (UCN-LI) in the human brain was studied by radioimmunoassay and was compared with that of corticotropin-releasing hormone (CRH). In addition, the expression of UCN mRNA was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) method. UCN-LI was detected in every region of brain examined, including hypothalamus, pons, cerebral cortex, and cerebellum. The concentrations of UCN-LI in the human brain were approximately 3 pmol/g wet weight in any brain region, and no marked regional difference was noted. On the other hand, the highest concentrations of CRH-LI were found in the frontal cortex, temporal cortex, and hypothalamus and the lowest in the pons. Reverse phase high-performance liquid chromatography of the UCN-LI in the human brain extract showed two immunoreactive peaks; one peak eluting earlier and one in the position of synthetic human UCN. RT-PCR showed that UCN mRNA was expressed in every region of brain examined. These findings indicated that UCN and UCN mRNA were widely expressed in the human brain.
Peptides 02/1998; 19(4):643-7. · 2.43 Impact Factor
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ABSTRACT: We developed a specific and sensitive radioimmunoassay (RIA) for rat urocortin (rUcn) and investigated the tissue distribution and concentration of immunoreactive (IR-)Ucn in rats. Antiserum was obtained by immunizing rabbits with synthetic rUcn21-35 coupled with bovine thyroglobulin. 125I-[Tyr]18-rUcn19-37 was used as the tracer. The RIA detected synthetic rUcn1-40 as low as 0.4 fmol/tube, and did not cross-react with other corticotropin-releasing factor-related peptides. IR-Ucn was widely distributed in central nervous system, endocrine organs, and digestive system. Its concentration was highest in pituitary (11.0 +/- 1.36 pmol/g.w.w., mean +/- SEM, n=4). Reverse-phase HPLC revealed that hypothalamic IR-Ucn had similar chromatographic mobility to synthetic rUcn1-40. However, bilateral adrenalectomy did not influence the hypothalamic IR-Ucn content. Our results suggest that Ucn may play important roles in various tissues in normal rats, but not behave as a hypothalamic hypophysiotropic factor in mediating adrenocorticotropin secretion in adrenalectomized rats.
Life Sciences 02/1998; 62(9):807-12. · 2.53 Impact Factor
