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Biomedical subjects

K Tanigawa

Publications and source records attributed to K Tanigawa.

At least 109 records · Page 6Linked to original sources

Differential insulin secretory activity in rat pancreatic islets and HIT cells.

We compared insulin secretory activity from rat pancreatic islets with that from a hamster beta-cell line (HIT-T). Insulin release from HIT cells was maximally stimulated with glucose at a concentration of 11.1 mM, and rather inhibited by higher concentrations of glucose. Blunted insulin release induced by glucose was shown in the isolated rat islets exposed to either streptozotocin (2.2 mM) for 30 min or alloxan (2 mM) for 5 min, whereas glucose-induced insulin release from HIT cells was not affected by pre-treatment with such beta-cell toxin. When pancreatic islets and HIT cells were cultured for 7 days with 10 mM nicotinamide, an inhibitor of poly (ADP-ribose) synthetase, glucose-induced insulin release from the islets was inhibited, whereas insulin release from HIT cells was rather enhanced. Insulin release induced by either arginine or leucine was also enhanced in HIT cells cultured with nicotinamide. These findings indicate that the multiple components of insulin stimulus-secretion coupling in HIT cells are considerably different from those in rat pancreatic islets.

Alloxan↗

Alcohol ingestion enhances hepatocarcinogenesis induced by synthetic estrogen and progestin in the rat.

We examined the effect of alcohol ingestion on rat hepatocarcinogenesis induced by oral administration of synthetic female hormones, 0.075 mg of ethynylestradiol (EE) and 6.0 mg of norethindrone acetate (NA), everyday for 12 months to Wistar rats. Concomitant administration of 10% ethanol in drinking water resulted in the development of hepatocellular carcinoma (HCC) in 40.8% in female rats and 11.8% in male rats at 12 months, although the incidences of HCC following hormones administration alone were 8.0% in female rats and 0% in male rats. The incidence and the number of hyperplastic nodules in rats with concomitant alcohol treatment were significantly higher than that in rats with hormone treatment alone. The additional alcohol administration significantly increased the values of nuclear and cytosol estrogen receptors at 4 months. Synthetic female hormones and/or alcohol treatment also significantly increased the value of cytosol progesterone receptor at 4 months. 32P-postlabeling analysis of liver DNA revealed that alcohol enhanced the DNA adduct formation induced by hormones. Consequently, alcohol may affect rat hepatocarcinogenesis caused by synthetic female hormones in enhancing cell-proliferating activity via estrogen and progesterone receptors, and DNA adduct formation induced by synthetic female hormones.

Alcohol Drinking↗

[Diagnosis and surgical treatment for endocrine tumors of the pancreas].

Clinical features, diagnostic accuracy of imaging study, and the outcome of surgical treatment for endocrine tumors of the pancreas were analyzed in 12 patients who underwent surgery for the past 16 years and 11 months. The 12 cases were classified into two groups: functioning tumors in 8 (insulinoma in 7 including one malignant case, and malignant glucagonoma in one), and nonfunctioning tumors in 4 including 3 malignant cases. In functioning tumors, tumor size was 2 cm or less in 6 benign cases, but 5 cm or more in 2 malignant cases. In nonfunctioning tumors, tumor size was larger, ranging from 3.5 to 8.0 cm. Diagnostic accuracy for localization of functioning tumors was 66.7% for US, 75.0% for CT, 66.7% for endoscopic retrograde pancreatography (ERP), and 50.0% for selective angiography, while all nonfunctioning tumors could be detected by any diagnostic imagings. Percutaneous transhepatic portal venous sampling for immunoreactive insulin was very helpful to localize insulinoma. Stenosis or obstruction of the main pancreatic duct on ERP and arterial encasement on angiography highly suggested a malignant tumor. Even for malignant cases with liver metastasis, resection of the primary tumor with debulking of metastatic disease or intraarterial infusion chemotherapy was considered to prolong patient prognosis.

Adult↗

Endoscopic removal of foreign bodies in the mentally and physically handicapped.

Although foreign bodies of the gastrointestinal tract are common in children, they are rare in the adult. Complications of the foreign bodies are well recognized to be a cause of obstruction, bleeding and perforation of the intestine, or furthermore, they sometimes lead to death unfortunately. On the other hand, it is very difficult to diagnose and treat foreign bodies in the handicapped because of disability of complaining the symptoms. This paper reports a 31-year-old severe handicapped man suffering from foreign bodies in the esophagus and the small intestine, and was successful removed by endoscope.

Adult↗

Diagnostic difficulty in a case of heterotopic pancreatic tissue of the ileum.

We describe a case of heterotopic pancreatic tissue of the ileum causing acute gastrointestinal tract bleeding. It was initially clearly demonstrated as an ileal polyp preoperatively by radiologic means. Exploratory surgery was performed, and the segment of ileum containing the mass was resected. Histopathologic examination of the lesion revealed heterotopic pancreatic tissue of Heinrich type II. There was no histological evidence of acute or chronic pancreatitis, but erosion was confirmed at the tip of the mass. Even symptomatic heterotopic pancreatic tissue of the ileum may give difficult diagnostic problems. The present case is reported to show the possibility of diagnosing rare abnormalities of the ileum.

Choristoma↗

Magnetic resonance imaging detection of aortic and pulmonary artery wall thickening in the acute stage of Takayasu arteritis. Improvement of clinical and radiologic findings after steroid therapy.

OBJECTIVE: Early diagnosis of Takayasu arteritis in the acute stage (prepulseless stage) is extremely difficult. Identification of a useful approach to detecting the initial changes of arteritis is therefore desirable. METHODS: Careful clinical examination of a young woman with persistent fever and dry cough revealed faintly audible bruits at the cervical, supraclavicular, and abdominal regions. Aortographic features suggested thickening of the wall of the descending thoracic aorta. Magnetic resonance imaging (MRI) of this area was diagnostic. RESULTS: MRI demonstrated involvement of the ascending aorta and right main pulmonary artery. Steroid therapy (prednisolone 60 mg/day) induced dramatic clinical and radiologic improvement in 2 months. CONCLUSION: This is the first report of MRI-documented reduction in the thickness of the walls of both the aorta and the pulmonary artery following steroid therapy.

Acute Disease↗

An inhibitor of sweet taste response modulates glucose-induced phosphoinositide breakdown in rat pancreatic islets.

We studied the effect of a specific-competitive inhibitor of the sucrose taste response, p-nitrophenyl-D-glucopyranoside (PNP-Glu) on insulin release and phosphoinositide metabolism in rat pancreatic islets. The alpha-anomer, but not the beta-anomer, of PNP-Glu at a concentration of 5 mM inhibited insulin release induced by 10 mM glucose. Islets were labeled by exposure for 2 h to 10 uCi of myo-[2-3H] inositol solution supplemented with 2.8 mM glucose. Forty islets were then incubated in the presence of 10 mM LiCl, 1 mM inositol and 10 mM glucose with or without the anomers of PNP-Glu. [3H] radioactivity in the incubation medium remained significantly greater in the presence of the alpha-anomer of PNP-Glu than in the presence of glucose alone after 5- and 20-min incubation. The inositol monophosphate levels in the islets incubated with glucose alone were increased more than in the islets with alpha-anomer. The beta-anomer of PNP-Glu did not change either glucose-induced insulin release or phosphoinositide breakdown. A patch-clamp study revealed that neither anomer affected the glucose-dependent ATP-sensitive K(+)-channels. These results indicate that the anomeric preference for glucose in insulin release in the pancreatic islets is closely associated with phosphoinositide breakdown.

Animals↗

Acute adrenal insufficiency due to symptomatic Rathke's cleft cyst.

A 65-year-old Japanese man who suffered from secondary hypopituitarism due to Rathke's cleft cyst is reported. Although computed tomography failed to detect any pituitary abnormality, magnetic resonance imaging demonstrated the presence of a cystic intrasellar mass, initially suggesting craniopharyngioma or abscess. Operative findings revealed Rathke's cleft cysts within the pituitary fossa which resulted in secondary hypopituitarism. Among cases of secondary hypopituitarism with abnormal findings in the pituitary, symptomatic Rathke's cleft cysts should be included in the differential diagnosis of adrenal insufficiency.

Adrenal Insufficiency↗

Impaired glucose priming of insulin secretion from perfused pancreas in aged female rats.

Effects of age and glucose levels on insulin secretion and synthesis were studied in the perfused pancreas of young (2-month-old) and older (10-month-old) female Wistar rats. Insulin secretion induced by 16.7 mM glucose showed a triphasic pattern: an early spike and fall (first phase, 0-6 min), followed by a sustained gradual increase (second phase, 7-120 min) and a gradual decreased release thereafter (third phase, 121-360 min) during the perfusion period of 360 min. First and second phase insulin secretion, but not third phase, were lower in older rats than in young rats. Insulin synthesis in old rat pancreas perfused with 16.7 nM glucose for 360 min was much greater than that of young rats. Second phase insulin secretion was restored to comparable levels by 28 mM glucose in older rats. Repeated pulses of 28 mM glucose potentiated subsequent insulin secretion in young rats, but not in older rats. These findings provide further evidence that sensitivity to glucose in pancreatic B cells is altered by aging.

Age Factors↗

Systolic and diastolic left ventricular dysfunction in middle-aged asymptomatic non-insulin-dependent diabetics.

Radionuclide ventriculographic studies were performed at rest and during exercise in 15 middle-aged asymptomatic patients with non-insulin-dependent diabetes mellitus (NIDDM) whose mean age was 58.7 +/- 10.5 years (mean +/- SD), and in 10 age- and sex-matched normal control subjects. The patients had neither clinical evidence of cardiovascular diseases nor obvious perfusion defects during maximal exercise testing with thallium-201 myocardial scintigraphy. The average left ventricular ejection fraction (LVEF) at rest was 69.1 +/- 5.3% in the diabetic patients and 65.6 +/- 4.2% in the control subjects, and during exercise, the average LVEFs were 68.3 +/- 6.9% and 72.1 +/- 5.0%, respectively. The changes in LVEF during exercise were -0.7 +/- 7.6% in the diabetic group and +6.5 +/- 2.6% in the control group (p < 0.01). However, the filling fraction during the first third of diastole at rest was significantly less in the diabetic group than in the control group (p < 0.05), the time to peak filling rate (TPF) was longer, and the TPF/R-R, normalized by the R-R interval and expressed as a percentage, was greater in the NIDDM patients than in the control subjects. There was close correlation between the abnormal response of LVEF to exercise and the reduced early diastolic filling in the diabetic patients. We concluded that 1) not only the response of LVEF to exercise but also the early left ventricular diastolic filling at rest are impaired in middle-aged asymptomatic NIDDM patients, and 2) some common factors could cause dysfunction of both the systolic and diastolic left ventricles in NIDDM patients, possibly latent global myocardial ischemia or metabolic myocardial disturbances.

Adult↗

Inositol cycling and phosphoinositide metabolism in rat pancreatic islets.

The effects of extracellular inositol and LiCl on intra-islet inositol cycling were investigated in isolated rat islets. Islets were cultured for 7 days in inositol-free RPMI 1640 containing 11.1 mM glucose and labeled with 3.7 MBq myo-[2-3H] inositol for the final 3 days. The labeled islets were then perifused under various conditions. There was a persistent increase in [3H] efflux from labeled islets stimulated with 16.7 mM glucose for 60 min. Addition of 5 mM inositol resulted in marked release of [3H] from islets and a decrease in radioactive inositol-lipid. When islets were perifused with 5 mM LiCl, the glucose-induced efflux of [3H] was greatly inhibited. The inhibitory effect of LiCl on [3H] efflux was partially corrected by the addition of 5 mM inositol. A prominent effect of LiCl was an increase in inositol monophosphate, indicating increased phospholipase C activity. This was detected within 5 min after glucose stimulation. The present data suggest that there is always very active intra-islet inositol cycling and that glucose can augument inositol-lipid metabolism.

Animals↗

Effect of aging on the sensitivity of pancreatic beta-cells to insulin secretagogues in rats.

Glucose-stimulated insulin release from rat pancreas is known to be blunted by aging. In the present study, we examined the effect of aging on insulin release induced by various secretagogues using the isolated perfused pancreas of female rats. Insulin release from the perfused pancreas in response to 16.7 mM glucose in 8-month-old rats (older rats) was much less than that in 2-month-old rats (young rats). The first phase of insulin release after glucose stimulation was attenuated in older rats. The addition of 0.1 mM 3-isobutyl-1-methylxanthine (IBMX) potentiated glucose-induced insulin secretion in both groups of rats. However, the second phase of insulin secretion in older rats was lower than that in younger rats. The phorbol ester 12-O-tetradecanoyl phorbol ester (TPA, 200 nM) enhanced both the first and the second phases of insulin release induced by glucose in both groups of rats. The amount of first phase insulin release induced by TPA with glucose in young rats was greater than that in older rats, whereas the second phase of insulin release was similar in both groups of rats. On the other hand, tolbutamide (200 uM) similarly stimulated the first phase of insulin release in both age groups of rat. In addition, the amount of cumulative insulin secretion induced by tolbutamide during the second phase was slightly but significantly greater in older rats than in young controls. Insulin content in the pancreas was significantly greater in older rats than in young rats and increased after the stimulation with TPA and tolbutamide.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

Effect of diabetes mellitus on levels of atrial natriuretic hormone in plasma and the right atrium in the non-obese diabetic mouse.

Atrial natriuretic hormone (ANH) levels in plasma and the right atrium of non-obese diabetic mice in the decompensated diabetic state were investigated by radioimmunoassay and histological examination. Severely diabetic mice, with blood glucose levels over 33.6 mmol/l showed significantly higher hematocrit, plasma sodium and calculated plasma osmolarity than the age-matched normoglycemic mice. The plasma ANH levels in diabetic mice were significantly lower (17.5 pmol/l) than those in normoglycemic mice (43.6 pmol/l). The ANH concentrations in the right atrium were 26.6 mg/g protein in the diabetic and 11.2 mg/g protein in the normoglycemic mice. The right atrium in the diabetic mice showed much wider immunohistochemical staining by anti-human ANH antiserum compared with the normoglycemic mice. An increase in the number of atrial specific granules in the diabetic mice was observed by transmission and scanning electron microscopy. Morphometrical analysis indicated that the number of granules increased to more than twice that in the normoglycemic mice. These findings indicate that plasma ANH decreases in diabetic mice. The store of right atrial ANH may be increased to compensate for the marked dehydration in severe diabetes.

Animals↗

Skeletal malformations in rat offspring. Long-term effect of maternal insulin-induced hypoglycemia during organogenesis.

We studied the effect of maternal hypoglycemia on skeletal growth in the offspring of nondiabetic and diabetic rats. Female Wistar rats were injected with streptozocin (30 mg/kg i.v.) 2-3 wk before mating, and diabetes was confirmed by an intraperitoneal glucose tolerance test. On postconception day 9.5 or 10.5, both control and diabetic dams received saline or Actrapid human insulin (400 mU/rat i.p.). Hypoglycemia (approximately 2.8 mM) was induced for 120 min in the insulin-treated mothers. Pregnancy was terminated on gestational day 20. Fetal bones and cartilage were double-stained with alizarin red S and alcian blue 8GS. Insulin-induced hypoglycemia caused delayed ossification in the fetuses of the control dams. The number of malformations, e.g., costal fusion waves, increased greatly. These effects were more striking in the fetuses of dams that had received insulin on day 10.5 rather than on day 9.5 of embryo development. This type of insulin-induced hypoglycemia further delayed ossification of the fetal bones in diabetic dams. The influence of maternal hypoglycemia on skeletal malformations and/or variations was greater in the fetuses of diabetic dams than in the fetuses of control dams. These data suggest that maternal hypoglycemia in early pregnancy has a striking effect on skeletal growth and malformations in fetuses. In addition, mild glucose intolerance in dams may amplify these hypoglycemic effects.

Animals↗