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Biomedical subjects

F Umeda

Publications and source records attributed to F Umeda.

At least 127 records · Page 7Linked to original sources
PubMed1990

Amylin release from perfused rat pancreas in response to glucose and arginine.

The effects of glucose and arginine on the release of amylin from the perfused rat pancreas were studied. Amylin, or islet amyloid polypeptide, is a 37-amino acid peptide isolated from pancreatic islet amyloid of patients with non-insulin-dependent diabetes mellitus (NIDDM). Glucose stimulated dose-dependently amylin release, showing a typical biphasic pattern. Additionally, 10 mM arginine in the presence of 5.5 mM glucose also stimulated amylin release. These findings suggest that amylin is a secretory protein and its release from the pancreas is regulated by glucose and other nutrients.

Animals↗
PubMed1990

Erythrocytes from diabetics with neuropathy have fewer sodium pumps.

Erythrocytes from diabetics with neuropathy had fewer binding sites for ouabain and, therefore, fewer sodium pumps than did erythrocytes from diabetics without neuropathy or from age-matched controls (P less than 0.001). Diabetics with neuropathy excreted in their urine significantly less C-peptide immunoreactivity (CPR) than those without neuropathy, which is a sign of lower endogenous insulin secretion levels. Significant positive correlations existed between the number of pumps and tibial motor nerve conduction velocity (MNCV) and urinary CPR in diabetics, and between urinary CPR and MNCV. This suggests that there is close correlation between the fall in the number of pumps in diabetics and diabetic neuropathy and insulin deficiency.

Biomarkers↗
PubMed1990

Effect of galanin on arginine-stimulated pancreatic hormone release from isolated perifused rat islets.

The effect of galanin on pancreatic hormone release was studied using isolated perifused rat pancreatic islets. In the presence of 100 mg/dl glucose, 10(-8) mol/L galanin significantly inhibited the basal somatostatin release compared with the perifusion without galanin, whereas there was no significant change in the basal insulin and glucagon release. However, under stimulation of 20 mmol/L arginine, 10(-8) mol/L galanin significantly enhanced glucagon release and suppressed insulin and somatostatin release. These effects disappeared immediately after cessation of galanin infusion. Additionally, 10(-8) mol/L galanin significantly enhanced the first and second phase of glucagon release stimulated by arginine, whereas arginine-stimulated insulin and somatostatin releases were significantly inhibited in both phases. In the cysteamine-treated rat islets, neither enhancement of glucagon release nor suppression of insulin release by galanin was reproducible. These findings indicate two possible explanations. First, it is suggested that the effects of galanin on insulin and glucagon release may be direct and reversed by non-specific effect of cycteamine. Secondly, it seems likely that galanin-enhanced glucagon release may be indirect and in part due to the concomitant somatostatin suppression. Galanin may have an important regulatory function on endocrine pancreas.

Animals↗
PubMed1990

Changes in phosphoinositide turnover, Ca2+ mobilization, and protein phosphorylation in platelets from NIDDM patients.

Enhanced platelet functions have been demonstrated in patients with non-insulin-dependent diabetes mellitus (NIDDM). This study evaluated abnormalities in platelet signal transduction in diabetic patients, including turnover of phosphoinositides, mobilization of intracellular Ca2+, and phosphorylation of 20,000- and 47,000-Mr proteins (P20 and P47). Washed platelets were obtained from 6 patients with NIDDM whose platelet aggregation rates were abnormally elevated (DM-A group), 11 NIDDM patients with normal platelet aggregation rates (DM-B group), and 8 age-matched healthy control subjects. The mass and specific radioactivity of phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol (PI), and phosphatidic acid (PA) in 32P-labeled platelets were not different among the three groups. Hydrolysis of PIP2, PIP, and PI; accumulation of PA; and phosphorylation of P20 in platelets stimulated by 0.05 U/ml thrombin were significantly increased in the DM-A group compared with the control or DM-B group. There was no difference in P47 phosphorylation among the three groups. On the contrary, P20 and P47 phosphorylation induced by 50 nM of 12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C, was significantly decreased in the DM-A group. Additionally, the intracellular free Ca2+ concentration [( Ca2+]i) was measured with the fluorescent Ca2+ indicator fura 2. Although the basal [Ca2+]i value was similar in the three groups, the rise in [Ca2+]i induced by 0.05 U/ml thrombin in the presence and the absence of extracellular Ca2+ was significantly higher in the DM-A group than the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Decreased VIP content in peripheral nerve from streptozocin-induced diabetic rats.

After induction of diabetes with streptozocin (STZ-D) in rats, we measured vasoactive intestinal polypeptide (VIP) content in sciatic nerve and spinal cord obtained from nondiabetic, untreated STZ-D, and insulin-treated STZ-D rats. Eight weeks after the onset of diabetes, caudal nerve conduction velocity (NCV) in the untreated STZ-D rats (n = 13) was slower than in the controls (n = 11; mean +/- SE 30.9 +/- 0.6 vs. 41.4 +/- 1.8 m/s, P less than 0.001). The decrease in NCV was less marked in the insulin-treated STZ-D rats (n = 11; 36.3 +/- 0.9 m/s, P less than 0.05 vs. control). VIP content in sciatic nerve decreased in the untreated STZ-D rats (1.33 +/- 0.23 ng/g wet wt) compared with the other groups (control, 3.10 +/- 0.44, P less than 0.01; insulin-treated STZ-D, 2.44 +/- 0.55, P less than 0.05). However, in spinal cord, VIP content was not significantly different among the three groups. The VIP levels in sciatic nerve showed a positive correlation with NCV (r = 0.430, P less than 0.01). In addition, an inverse correlation between VIP levels and blood glucose levels was observed (r = -0.5624, P less than 0.001). NCV was also inversely correlated with blood glucose levels (r = -0.7662, P less than 0.001). Together with a previous morphological study, these findings suggest a possible causal relationship between reduced VIP content and diabetic neuropathy.

Animals↗
PubMed1990

Effects of captopril on urinary excretion of albumin and prostaglandins in patients with diabetic nephropathy.

Recently the beneficial effects of captopril (angiotensin-converting-enzyme inhibitor) on diabetic nephropathy, especially proteinuria, have been reported by some investigators. The mechanism whereby proteinuria is reduced, however, have not been clarified yet. The present study was undertaken to evaluate the effects of captopril on urinary albumin excretion in relation to urinary prostaglandins (PGs) excretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Captopril (37.5 mg/day) was orally administered to 13 diabetic patients for an eight-week period. A single administration of captopril (12.5 mg) was performed in the same patients. The spot urine samples were collected in the early morning and 2 hr after the single administration of captopril. The albumin index (mg/gram-creatinine) was markedly decreased in eight patients (Group A) within four weeks, but no decrease was found in five patients (Group B). Furthermore, in Group A, by the single administration of captopril urinary excretions of 6-keto-PCF1 alpha (a stable metabolite of PGI2) and PGE2 were significantly (p less than 0.05) increased while urinary TXB2 (a stable metabolite of TXA2) excretion did not change significantly. The urinary 6-keto-PGF1 alpha/TXB2 ratio, which is significantly (p less than 0.05) low in diabetic patients was significantly (p less than 0.01) increased up to the normal value in Group A. In Group B, however, there were no significant changes in urinary PGs excretion. These results suggest that captopril enhances the production of intrarenal vasodilatory PGs such as PGI2 and PGE2, which may be deeply involved in the reduction of intraglomerular capillary pressure and urinary protein excretion in diabetic patients.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Effects of vitamin E administration on platelet function in diabetes mellitus.

A decrease in the vitamin E content of human diabetic platelets is closely associated with the accelerated platelet aggregation and platelet prostaglandin metabolism seen in patients with diabetes mellitus. We investigated the effect of vitamin E supplementation on these abnormalities of physiological function and prostaglandin metabolism in 14 non-insulin dependent diabetics with proliferative retinopathy. ADP-induced platelet aggregation was inhibited in vitro by the addition of vitamin E in a dose-dependent manner. However, in lower concentrations considered to be physiological doses in vivo, significantly greater inhibition was observed in diabetic platelets than in the control platelets. Next, alpha-tocopheryl nicotinate was administered to diabetics at a daily dose of 600 mg. The platelet vitamin E content was restored to control levels in 13 of the 14 patients after 2-4 weeks of daily administration. The ADP-induced platelet aggregation rate, platelet thromboxane B2 (TXB2, a stable metabolite of TXA2, a vasoconstrictor production, and plasma TXB2 level were low in all 14 diabetics. In contrast, plasma 6-keto-PGF 1 alpha (a stable metabolite of PGI2, a vasodilator) was significantly increased and therefore the 6-keto-PGF 1 alpha/TXB2 ratio in plasma was restored to within normal limits. These results indicate that vitamin E may improve platelet function and prostaglandin metabolism in diabetes mellitus and may be able to provide further beneficial effects in relation to the development of diabetic vascular complications.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Antithrombin III stimulates prostacyclin production by cultured aortic endothelial cells.

Prostacyclin (PGI2) is a potent vasodilator and an inhibitor of platelet aggregation. We found that antithrombin III (AT III), an anticoagulant present in circulating blood, stimulated PGI2 production by cultured bovine aortic endothelial cells in a dose- and time-dependent manner. The stimulation of PGI2 production by AT III was observed at physiological concentrations and was inhibited by the addition of anti-AT III antiserum and heparin. These results suggest that AT III may stimulate PGI2 production by binding to heparin-like molecules on the endothelial cell membrane.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Decrease in insulin binding to aortic endothelial cells cultured with high glucose concentration.

We studied the effects of glucose on specific insulin binding to cultured endothelial cells from the bovine aorta. We cultured the cells in Dulbecco's modified Eagle's medium, containing 100 or 300 mg/dl glucose or 100 mg/dl glucose plus 200 mg/dl mannitol. We added 125I-insulin to monolayers of these cells and counted the radioactivity resulting. Specific insulin binding increased with time and dosage. Maximal binding resulted from 0.17 nM 125I-insulin being incubated for 30 min at 37 degrees C, and amounted to 0.35% per 10(5) cells being bound in cultures of 100 mg/dl glucose. The higher concentration of glucose led to significantly less binding (P less than 0.05) (0.24 +/- 0.03% vs. 0.38 +/- 0.02%, n = 6). The addition of mannitol, on the other hand, did not affect binding. All three incubation conditions produced curvilinear competition curves. Scatchard analysis showed that insulin bound significantly less (P less than 0.05) to endothelial cells in 300 mg/dl glucose than to those in 100 mg/dl glucose (4.0 +/- 1.2 nmol/l vs. 12.8 +/- 3.1, n = 6, mean +/- SEM). Insulin binding capacity, however, did not change. We conclude that glucose can reduce insulin binding to endothelial cells and that it may reduce receptor-related insulin transport into and out of the cells.

Animals↗
PubMed1989

Reduced stimulatory activity on prostacyclin production by cultured endothelial cells in serum from aged and diabetic patients.

Reduced prostacyclin (PGI2) generation by the vascular wall shows a close relationship with the development of atherosclerosis. The present study found plasma-derived serum (PDS) to contain an activity which stimulated PGI2 production by cultured bovine aortic endothelial cells. Diabetic and aged patients with atherosclerotic disease were examined for abnormalities in that stimulatory activity in PDS. PDS obtained from both diabetics (NIDDM) and aged patients showed a significant reduction in the stimulation of PGI2 production by cultured bovine aortic endothelial cells compared with age-matched controls and young healthy volunteers, respectively. It was suggested that the reduced PGI2 stimulatory activity in PDS may be one of the pathogenic mechanisms of vascular lesions such as atherosclerosis in diabetics and aged humans.

Adult↗
PubMed1989

Abnormality in prostacyclin-stimulatory activity in sera from diabetics.

A reduction in prostacyclin (PGI2) production by vascular wall may cause platelet hyperaggregability in diabetics, which is considered to be a possible pathogenesis of diabetic vascular complications. In the present study, the presence of PGI2-stimulatory activity (PSA) in rat and human plasma-derived serum (PDS) was confirmed by cultured bovine aortic endothelial cells. PSA in PDS was significantly decreased in streptozotocin-induced diabetic rats and in patients with non-insulin-dependent diabetes mellitus (NIDDM). PDS from patients with NIDDM showed less PSA prior to the clinical onset of diabetic vascular complications, such as retinopathy and proteinuria. The reduction in PSA was still observed in dialyzed PDS from the patients with NIDDM. The nondialyzable PSA was heat-stable at 56 degrees C for 30 minutes and partially stable at 100 degrees C for five minutes. This activity was not extractable with diethylether and was precipitable with trichloroacetic acid. The study of Sephadex G-50 column chromatography showed that a major part of PSA in dialyzed PDS was found in the area of the molecular weight of 12,000 to 17,000 daltons. In conclusion, the reduction in PSA from diabetics may cause a reduction of PGI2 production by vascular wall, subsequently contributing to the development of diabetic vascular complications.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Serum fructosamine in assessment of diabetic control and relation to thyroid function.

Measurement of serum fructosamine using a Roche kit is a simple and reliable method for the estimation of glycated serum proteins. The value of serum fructosamine can be affected by hyperglycemia in diabetics and an abnormal turnover rate of serum protein in patients with thyroid dysfunction. We measured the serum fructosamine level in 18 normal control subjects, 71 diabetics (8 IDDM, 63 NIDDM) and 46 non-diabetic untreated patients with thyroid dysfunction (28 hyperthyroidism, 18 hypothyroidism). The serum fructosamine level was significantly increased in the diabetics compared with the normal control subjects (3.84 +/- 0.15 mmol/l vs 2.58 +/- 0.08; mean +/- SE, P less than 0.01). The serum fructosamine level in the diabetics was positively correlated with the fasting plasma glucose and HbAlc level, showing the highest correlation with fasting plasma glucose at 2 weeks before and with the HbAlc level at 2 weeks after serum fructosamine measurement. In the patients with thyroid dysfunction, the serum fructosamine level in hyperthyroidism (2.08 +/- 0.03 mmol/l) and hypothyroidism (3.11 +/- 0.07 mmol/l) were significantly lower (P less than 0.001) and higher (P less than 0.001) than the normal control subjects (2.58 +/- 0.08 mmol/l), respectively. Furthermore, the serum fructosamine level in these patients was negatively correlated with the level of serum thyroid hormones such as T3 (P less than 0.001) and T4 (P less than 0.001). It is concluded that measurement of serum fructosamine is clinically useful for the evaluation of shorter-term glycemic control in diabetics, but its level for diabetic patients with thyroid dysfunction must be cautiously interpreted.

Adult↗
PubMed1989

A new case of familial hyperproinsulinemia.

We reported a case with increased serum immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR). The molar ratio of IRI to CPR was also increased. The propositus was diabetic with background retinopathy and neuropathy. No antibody to insulin or insulin receptor was detected in his serum and his insulin resistance was not so remarkable. When the serum was fractionated by gel filtration, about 90% of total IRI was recovered in the fraction where biosynthetic human proinsulin was eluted. The major part of the CPR was also recovered in the same fraction as proinsulin-like material. His daughter, 28 years old, a non-obese female, also had high IRI, CPR and a high molar ratio of IRI to CPR. A gel filtration study demonstrated the same elution profile as the propositus. Tryptic digestion failed to convert the proinsulin-like material from the propositus to insulin in a sufficient quantity to convert human proinsulin to insulin. These data strongly suggest that this family is a new case of familial hyperproinsulinemia, and the defect resides in the proinsulin molecule, not in the converting enzymes.

Adult↗
PubMed1989

Albumin index in spot urine from outpatients with noninsulin-dependent diabetes mellitus.

The albumin index (mg/g . creatinine) was determined in untimed spot urine collected in the early morning from 92 randomly selected outpatients with noninsulin-dependent diabetes mellitus (NIDDM). The patients were divided into three groups: 49 patients with normo-albuminuria (albumin index less than 9.1), 24 with micro-albuminuria (albumin index between 9.1 and 100), and 19 with overt-albuminuria (albumin index over than 100). With diabetic duration, the frequency of the patients with overt-albuminuria was increased, but that with normo-albuminuria was decreased. The patients treated with only a diet almost showed normo-albuminuria. In contrast, micro-and overt-albuminuria were found more frequently in the patients treated with oral hypoglycemic agents or insulin. Micro- and overt-albuminuria were found more frequently in the patients with poor glycemic control than in those with good glycemic control. The urinary albumin index was significantly high in the micro-albuminuric patients with poor glycemic control. Similarly, micro- and overt-albuminuria were found more frequently in the patients associated with diabetic retinopathy or neuropathy than in those without diabetic complications. In addition, overt-albuminuria was found more frequently in the patients with hypertension. The urinary albumin index was significantly high in the overt-albuminuric patients with hypertension. In conclusion, the determination of the albumin index in spot urine may be outpatients with NIDDM.

Albuminuria↗
PubMed1989

Effect of aldose reductase inhibitor (Ponalrestat) on erythrocyte Na,K-ATPase activity in non-insulin-dependent diabetic patients with polyneuropathy.

The binding capacity of ouabain to erythrocyte Na,K-ATPase was determined to analyze alterations in this enzyme activity in non-insulin-dependent diabetic patients. A significant (p less than 0.001) reduction of the binding capacity of ouabain was found in erythrocytes obtained from the diabetic patients with polyneuropathy (0.51 +/- 0.02 pmol/10(9) erythrocytes, m +/- SE, n = 14) as compared with the patients without neuropathy (0.67 +/- 0.02, n = 14) or age-matched control subjects (0.71 +/- 0.04, n = 11). Accordingly, the effect of an aldose reductase inhibitor (ARI; Ponalrestat) on erythrocyte Na,K-ATPase activity was studied following two or three months oral administration in seven of the diabetic patients with polyneuropathy. After treatment with Ponalrestat the mean binding capacity of ouabain was significantly increased from 0.53 +/- 0.04 to 0.57 +/- 0.03 (p less than 0.05 by paired t-test). Furthermore, enzyme kinetics showed that in normal subjects the apparent Km and Vmax of erythrocyte membrane Na,K-ATPase were 0.51 +/- 0.07 mM (n = 5, m +/- SE) and 7.19 +/- 0.27 nmol Pi/mg protein/min (n = 5, m +/- SE), respectively. The Vmax with 3 mM ATP was significantly (p less than 0.05) decreased in the diabetic patients with polyneuropathy as compared with age-matched control subjects. However, the apparent Km did not change. Finally, the in vitro effect of Ponalrestat was examined in erythrocyte membrane fractions from the diabetic patients with polyneuropathy. The activity of erythrocyte membrane Na,K-ATPase was found to be directly stimulated about 1.2 fold by the addition of pharmacological doses of Ponalrestat (10(-10), 10(-8), 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1989

Effect of islet-activating protein (IAP) on glucagon release from isolated perifused rat islets.

The present study was undertaken to evaluate the effect of islet-activating protein (IAP) on glucagon release using perifused isolated rat pancreatic islets. Glucagon release stimulated by 20 mM arginine was significantly enhanced in the IAP-treated rat pancreatic islets as compared with the IAP-untreated controls. Additionally, the effect of 1 ng/ml somatostatin on glucagon release was examined during ongoing stimulation by arginine. In the IAP-treated islets somatostatin inhibits glucagon secretion to the same extent as in the IAP-untreated islets. These results demonstrate that IAP potentiates arginine-induced glucagon release from perifused rat pancreatic islets, and IAP fails to antagonize the inhibitory effect of somatostatin in the pancreatic A cell.

Animals↗