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T Wasada

Publications and source records attributed to T Wasada.

At least 55 records · Page 3Linked to original sources
PubMed1992

An insulin-like growth factor II-producing histiocytoma associated with hypoglycemia: analysis of the peptide, its gene expression, and glucose transporter isoforms.

An insulin-like growth factor II (IGF-II)-producing histiocytoma was detected in a patient presenting with the classical findings of tumor-related hypoglycemia (low serum insulin and IGF-I concentrations, glucose intolerance, and only modestly increased serum IGF-II levels). Acid-gel filtration of serum extracts showed a single peak of IGF-II immunoreactivity that emerged at the same site as the 125I-labeled human IGF-II standard. High-performance liquid chromatography (HPLC) analysis of the tumor IGF-II demonstrated that it had an identical retention time to that of recombinant human IGF-II. The tumor IGF-II content was extremely high, messenger RNA (mRNA) for IGF-II showed a 100-fold increase in expression compared with normal human liver tissue. Of special interest, a newly identified exon (hE1) was shown to be predominantly expressed in the tumor by Northern blot analysis using leader exon-specific rat IGF-II complementary DNA (cDNA) probes. Although the significance of this finding remains uncertain, this is the first evidence of a new transcription unit in the human IGF-II gene. In addition, immunoblotting showed that the levels of the glucose transporters, GLUT1 and GLUT4, in the tumor were low and undetectable, respectively. This finding makes it unlikely that increased glucose consumption by the tumor accounted for the hypoglycemia in this patient. This case report provides an interesting insight into the pathophysiology of tumor-induced hypoglycemia and new evidence of the abnormal regulation of IGF-II gene expression in human tumors.

Animals↗
PubMed1992

Transient extreme insulin resistance in shock during diabetic ketoacidosis.

Transient extreme insulin resistance was encountered during an episode of diabetic ketoacidosis (DKA) in an insulin-treated diabetic patient. On admission, the plasma glucose level was 1241 mg dl-1 and arterial blood pH 6.895 with HCO3- 4.7 mEql-1. An intravenous bolus injection of 20 units, followed by continuous infusion of 20 units h-1 of short-acting regular human insulin, was instituted. Ischemic myocardial changes were noted on the initial electrocardiogram, therefore fluid replacement was limited to 1,000 ml of 0.9% saline solution in the first hour. As the plasma glucose level declined by only 203 mg dl-1 (41 mg dl-1 h-1) in the first 5 h, the insulin dose was doubled every 2 h. At hour 4, the patient developed circulatory shock which required vasopressor support and respiratory assistance. A plasma glucose level of 300 mg dl-1 was not achieved until the total dosage of insulin amounted to 91,580 units at hour 25. Insulin resistance was not observed from that point on. The patient had neither insulin antibodies nor anti-insulin receptor antibodies in serologic testing. The insulin binding characteristics of the patient's erythrocytes were similar to those from healthy controls both with and without experimental acidosis and with a high level of beta-hydroxybutyrate. Among multiple potential factors, the severe shock associated with DKA has been considered as a primary cause of the transient severe insulin resistance in this case.

3-Hydroxybutyric Acid↗
PubMed1991

Identification of a novel transcription unit in the human insulin-like growth factor-II gene.

The human insulin-like growth factor-II (hIGF-II) gene has until now been thought to be composed of eight exons, including three independent leader exons. In the present study two additional exons, one leader exon and one alternatively used ordinate exon, have been newly identified. They were abundantly expressed in human histiocytoma tissue, generating mRNA species of about 5.0 kb in length. The new leader exon shows significant sequence similarity with the rE1 exon, previously reported to be transcribed only in the rat, and is mapped at nearly the same genomic location as in the rat. On the other hand, sequence similarity with another exon in the corresponding region of the rat genome was also found. It was, however, obvious that the rat sequence would not work as an active exon, since both splice acceptor and donor sites were deviated considerably from the consensus sequences. It has thus become apparent that the complex transcription unit of a single-copy hIGF-II gene comprises at least 10 exons, including four leader exons, one alternative exon and three common protein-coding exons.

Amino Acid Sequence↗
PubMed1989

Insulin autoimmune syndrome associated with benign monoclonal gammopathy. Evidence for monoclonal insulin autoantibodies.

A 64-yr-old man with benign monoclonal gammopathy developed recurrent episodes of severe hypoglycemia but lacked evidence of insulinoma or exogenous insulin administration. The patient's plasma was found to contain anti-insulin antibodies and large amounts of extractable insulin (1110 microU/ml), which was identified as human insulin by high-performance liquid chromatography (HPLC). The anti-insulin antibodies consisted solely of IgG and lambda-light chains. Scatchard analysis of these antibodies revealed an almost straight-line relationship, with markedly low affinity and high capacity. An immune complex made of 125I-labeled insulin and the patient's antibodies emerged in a molecular-sieve HPLC as almost a single peak, suggesting a homogeneous antibody population. In addition, the patient's M protein was separately shown to be the IgG and lambda-light-chain type. We suggest that the insulin autoantibodies responsible for the spontaneous hypoglycemia in this patient are monoclonal and of M protein origin.

Antibodies, Monoclonal↗
PubMed1988

Reverse phase high performance liquid chromatographic analysis of circulating insulin in the insulin autoimmune syndrome.

Some patients with the insulin autoimmune syndrome have circulating insulin that is heterogeneous. We used reverse phase high performance liquid chromatographic analysis to identify the forms of plasma insulin in patients with this syndrome and compared the results with those in patients with insulin-treated diabetes and patients with hyperinsulinism. Under acidic conditions, free insulin dissociated from insulin antibodies eluted from Bio-Gel P-30 columns as a single peak. When such insulin fractions were applied to reverse phase high performance liquid chromatography, a major insulin peak emerged with the same retention time as standard human insulin in all six patients with the syndrome. In addition, a minor insulin peak was consistently found at relatively high acetonitrile concentrations. However, this hydrophobic insulin also was found in two of four insulin-treated diabetic patients and in one of two hyperinsulinemic patients who did not have insulin antibodies. Preliminary characterization of the variant insulin revealed that it has a molecular size between those of proinsulin and insulin and retains the immunoreactivity of insulin, but not C-peptide. It may be an aggregate of insulin molecule or proinsulin intermediates. Since the variant insulin was not found only in patients with the insulin autoimmune syndrome, it seems unlikely that an altered endogenously produced insulin induces the generation of autoantibodies to insulin in this syndrome.

Adult↗
PubMed1987

Hypersomatostatinemia in chronic renal failure.

Plasma concentrations of somatostatin-like immunoreactivity (SLI) were determined in uremic patients on maintenance hemodialysis. Plasma SLI levels were significantly (p less than 0.001) elevated in 26 diabetic uremic patients (67.1 +/- 6.8 pg/ml, mean +/- SE) and in 24 non-diabetic uremic patients (43.5 +/- 7.2 pg/ml), when compared with 60 healthy subjects (5.0 +/- 0.7 pg/ml). Paired pooled plasma from uremic patients before and after hemodialysis was subjected to a reverse-phase octadecasilyl-silica (C-18) cartridge and then the extract was gel filtered on a Sephadex G-25 column (1.6 X 90 cm). Both elution profiles showed two peaks of SLI which coeluted with synthetic somatostatin (SS)-28 and SS-14 markers, respectively. The SS-28-like immunoreactivity (LI) peak, which was estimated by using SS-14 as a reference standard, was 3-fold larger than that for SS-14 LI. On the basis of immunoequivalency of the two components in the present assay, SS-28 LI constitutes approximately 75% of circulating somatostatin. In conclusion, plasma SLI is substantially high in uremic patients of both diabetic and non-diabetic etiology and the SS-28 is a predominant form of circulating SLI in these patients, probably, in part, for a lower clearance of this molecule.

Chromatography, Gel↗
PubMed1986

Aberrant insulinoma in the duodenum.

A rare case of aberrant insulinoma in the duodenum is described. Hyperinsulinemia with typical hypoglycemic symptoms was induced by prolonged fasting. Selective angiography demonstrated a tumor supplied from the first branch of the jejunal artery, and duodenoscopy revealed a submucosal tumor at the third portion of the duodenum. An increase in venous plasma immunoreactive insulin concentration was evident in the vein draining from the tumor, by sampling through percutaneous transhepatic catheterization. Hypoglycemia was ameliorated after the removal of the submucosal tumor of the duodenum. Histologic and immunocytochemical characterization of the tumor showed an insulinoma, predominantly composed of cells with typical B-cell-like granules. The acid extract of the tumor contained 1.2 U/g of insulin, and this insulin, analyzed by reverse-phase high-pressure liquid chromatography, revealed that it had the same amino acid structure as that of human insulin.

Adenoma, Islet Cell↗
PubMed1986

Effect of glibenclamide on pancreatic hormone release from isolated perifused islets of normal and cysteamine-treated rats.

The effect of glibenclamide, a sulfonylurea agent, on islet hormone secretion, particularly on glucagon was studied using isolated perifused pancreatic islets of normal and cysteamine-treated rats. In normal rat islets, glibenclamide enhanced both insulin and somatostatin release in normoglycemic (50 mg/dL) and glucopenic (0 mg/dL) states, as well as under the condition of arginine stimulation. In contrast, glibenclamide stimulated glucagon release only transiently, then suppressed it in a sustaining manner in each state. In the cysteamine-treated islets, as expected, somatostatin concentrations in the perifusate remained unchanged during the infusion of arginine and/or glibenclamide. Under this condition, glibenclamide enhanced insulin release to the same extent as seen in normal islets, and again markedly inhibited glucagon release. These observations indicate that in isolated perifused rat pancreatic islets, glibenclamide suppresses glucagon secretion independently of D cell stimulation. It is concluded that glibenclamide may exert its inhibitory effect directly on A cell rather than through paracrine action of concomitant somatostatin release, and that the suppression of glucagon secretion by glibenclamide may, in part, contribute to the antidiabetogenic effect of this compound.

Animals↗
PubMed1986

Plasma fibronectin and platelet aggregation in diabetes mellitus.

Plasma fibronectin (FN) is a high-molecular weight glycoprotein produced by endothelial cells, fibroblasts, and other mesenchymal cells. Plasma FN levels were measured in non-insulin-dependent diabetics (NIDDM) (n = 42) and compared with age-matched control subjects (n = 20). Plasma FN levels were significantly higher in the NIDDM patients (44.2 +/- 2.2 mg/dl, mean +/- SE) than in the control subjects (31.2 +/- 2.2 mg/dl). In addition, the rate of platelet aggregation was studied in 23 of the 42 NIDDM patients. Interestingly, the plasma FN levels were significantly elevated, particularly in diabetic patients with enhanced platelet aggregation. It is suggested that elevated plasma FN may be closely related to the abnormality of platelet function in diabetics, which leads to diabetic vascular lesions.

Adult↗
PubMed1986

Plasma somatostatin response in normal and gastrectomized subjects.

The present work was undertaken to investigate a possible contribution of the stomach to plasma concentrations of somatostatin-like immunoreactivity (SLI) in humans. For this purpose, plasma SLI responses were determined in previously gastrectomized subjects during lipid-heparin induced elevation of plasma free fatty acids (FFA), which gave a consistent rise of plasma SLI in normal controls. Fasting plasma SLI levels in both the subjects with antral and total gastrectomy did not differ from the values in normal controls. Acute elevation of plasma FFA resulted in about 5-fold increase of plasma SLI above basal level in the controls. In contrast, in both the gastrectomy groups there was no significant rise in plasma SLI, despite a comparable elevation of plasma FFA levels. In conclusion, these findings demonstrate that the stomach, probably the antral region of the stomach, accounts for the most part of increase of plasma SLI when hyperfatty-acidemia is induced and suggest that following the stimulation by nutrients the stomach makes a greater contribution to plasma SLI levels than does the pancreas or extragastric intestinal tract in humans.

Adult↗
PubMed1984

Effect of prostaglandin synthetase inhibitors on platelet aggregation and thromboxane production in diabetes mellitus.

Platelet aggregation is known to be increased in diabetes mellitus, and the enhanced thromboxane production has been shown to be one of the causes of such abnormal platelet function. To investigate which step is activated in diabetic prostaglandin metabolism, three specific inhibitors of prostaglandin synthetases were used in this study, which were mepacrine, indomethacin and imidazole. Platelet aggregation induced by collagen was significantly increased accompanying enhanced thromboxane production in diabetics with proliferative retinopathy compared with age matched controls. Platelet aggregation in diabetics with proliferative retinopathy was less inhibited by the addition of each inhibitor compared with controls. However, there was no difference in inhibitory pattern of platelet aggregation among the three inhibitors. In addition, thromboxane production during aggregation in diabetics with proliferative retinopathy was significantly greater than that in controls by the addition of each inhibitor. Inhibitory patterns of thromboxane production did not differ among the addition of three inhibitors. It is concluded that enhanced thromboxane production resulting in enhanced platelet aggregation would be related to diabetic vascular complications. This abnormal prostaglandin production can be due to the activation of general steps in prostaglandin metabolism in diabetic platelets, not of a specific enzyme.

Adult↗
PubMed1984

A clinical profile of insulin-dependent diabetes with islet cell cytoplasmic and cell surface antibodies.

Both islet cytoplasmic and cell surface antibodies (ICA and ICSA) were studied from the onset of diabetes to the honeymoon in an insulin-dependent diabetic patient. The patient, a 24-year-old male, was admitted to the hospital because of ketoacidotic hyperglycemic precoma. Continuous subcutaneous infusion of a small dose of insulin was carried out for a couple of days followed by NPH-insulin injection. The dose was gradually decreased and on the 45th day after the onset, an oral hypoglycemic agent was substituted for insulin. The patient was followed up after discharge from the hospital and his disease was controlled well by diet and a hypoglycemic agent until he caught a common cold. He was then admitted again to the hospital because of hyperglycemia, and insulin injection was performed. Both ICA and ICSA were found independently of each other during the course of the disease. The ICSA, which was quantitatively determined by immunoassay using 125I-protein A, closely paralleled the clinical profile. However, the levels of quantitative ICSA were higher than normal, even though the patient's diabetes reached the honeymoon stage. These results suggest that quantitative ICSA has a strong association with the clinical profile in IDDM, and it may be a "marker" of islet cell damage during the diabetic period or a parameter for diabetic prognosis.

Adult↗