Biomedical subjects

H Hirose

Publications and source records attributed to H Hirose.

At least 181 records · Page 10Linked to original sources

PubMed1996

[Articulatory function in patients receiving glossectomy followed by reconstruction with a recto-abdominal myocutaneous free flap].

Postoperative articulatory functions of patients with tongue cancer have been improved by reconstructive surgery with a radial forearm or recto-abdominal myocutaneous free flap. We examined the postoperative articulatory functions of 10 patients who received reconstruction with a recto-abdominal myocutaneous free flap after glossectomy. The functions were investigated by standardized tests, i. e. a quentionnaires, the 100 Japanese monosyllable speech intelligibility test and a single-word intelligibility test. A confusion matrix was obtained from the results of the monosyllable test. On the basis of resection sites, the present cases were divided into two types: an anterior type and a lateral type. The results are summarized as follows. There was no significant difference in the results of the quentionnareis between the two types. The mean score of the 100 Japanese monosyllable speech intelligibility test in cases of the anterior type was 48% and in those of the lateral type it was 62%. The mean score of the single-word intellibibility test in cases of the anterior type was 75% and in those of the lateral type it was 83%. In cases of the anterior type, dental and alveolar sounds were often confused with fricatives, whereas in the lateral type, velars sounds were often confused with affricates or flaps. These results suggest that our classification based on resection site was useful for investigating postoperative articulatory functions after partial glossectomy.

Adult↗

PubMed1996

S-cone pathway sensitivity in diabetes measured with threshold versus intensity curves on flashed backgrounds.

PURPOSE: To study sensitivity loss to short wavelength lights in patients with diabetes with or without retinopathy and to identify changes that cannot be attributed to preretinal screening. METHODS: Flash-on-flash thresholds were measured in 41 patients with diabetes and were compared to those in age-matched normals. A 50-ms, 1 degree blue test spot was presented simultaneously with a 500-ms, 2 degree blue flash. A bright yellow background isolated the S-cone system. RESULTS: The mean flash-on-flash threshold curve shifted up as the stage of retinopathy progressed in 16 patients with insulin-dependent diabetes mellitus (IDDM), including those without retinopathy. In 25 patients with noninsulin-dependent diabetes mellitus (NIDDM), those with preproliferative retinopathy revealed sensitivity loss; however, those with background retinopathy or without retinopathy showed no statistically significant change in sensitivity. CONCLUSIONS: The pattern of sensitivity loss in the patients with IDDM cannot be caused by changes in preretinal screening, including yellowing of the lens. Further, early functional changes in the patients with IDDM without retinopathy can be detected by this method.

Adolescent↗

PubMed1996

[Association of Epstein-Barr virus with primary malignant lymphomas of the digestive tract].

The association of Epstein-Barr virus (EBV) with 85 non-Hodgkin lymphomas of the digestive tract in nonimmunocompromised cases was investigated, using in situ hybridization technique to detect EBV encoded small RNAs in paraffin sections. 85 cases (83 B-cell type and 2 T-cell type) included 3 gingivas, 1 tongue, 3 palates, 10 tonsils, 43 stomachs, 2 jejunums, 12 ileums, 3 ileo-cecal regions, 5 colons and 3 rectums. Out of 85 cases, 4 (4.7%) were EBV-positive, comprising 1 B-cell lymphoma of the tonsil, 2 B-cell lymphomas of the stomach, and 1 T-cell lymphoma of the rectum. On the other hand, EBV-positive rate in nasal/nasopharyngeal lymphomas examined for comparison was very high, 81.8% (9 out of 11). These results show that EBV is associated with only a small proportion of lymphomas of the digestive tract in nonimmunocompromised case, suggesting the existence of the other oncogenetic factors in the pathogenesis of this group of lymphomas.

Adult↗

PubMed1996

Detection of myocardial ischemic injury during simple cold storage by measurement of myocardial electrical impedance.

The purpose of this study was to determine if graft viability during simple cold storage can be monitored from alteration of myocardial electrical impedance. Six anesthetized dogs underwent rapid cardiac extirpation and were placed in simple cold storage in saline for 12 hours. Myocardial electrical impedance was measured serially by use of a LCR meter and the changes of myocardial resistivity analyzed. Myocardial specimens were taken for myocardial ATP analysis and electron microscopic study during preservation. We investigated the correlation between myocardial resistivity and myocardial ATP content. Moreover in order to predict cardiac function after simple cold storage in saline, heterotopic cardiac transplantation in the neck was performed in mongrel dogs and left ventricular Emax (LV Emax) was measured with a micromanometer and conductance catheter method. It was then investigated whether or not it is feasible to predict cardiac function of the graft afer reperfusion from the changes in myocardial resistivity. Myocardial ATP remained above 50% of preischemic value 4 hours after preservation. Ultrastructural alterations of ischemia were observed in hearts preserved for 8 and 12 hours. In heterotopic cardiac transplantation, LV Emax at 120 minutes after reperfusion recovered to 94 +/- 13% of preischemic function in 4 hour-preserved heart, 72 +/- 10% in 8 hour-preserved heart. Percent recovery of LV Emax in the former was significantly higher than that in the latter (p<0.05). Turning points from reversible conditions to irreversible ones were between 4 and 8 hours based on myocardial ATP content, cardiac function after transplantation and morphological changes. With the time of preservation, resistivity began to increase in every dog and peaked during preservation. The time required to reach the peak point of resistivity ranged from 4 to 5.5 hours. Resistivity increase rate (RIR) decreased gradually during preservation and it was over 0.1 omega cm/min until a half-life of ATP. These results suggested that measurement of myocardial electrical impedance in the preserved heart should be feasible as an indicator of graft viability during preservation in heart transplantation.

Adenosine Triphosphate↗

PubMed1996

[A surgically treated case of ruptured true aortic arch aneurysm in association with Stanford type A chronic dissection].

A 72-year-old woman was admitted to our hospital because of hemosputum. Enhanced CT showed ruptured true aortic arch aneurysm. True aortic arch aneurysm ruptured at distal portion of aneurysm. The aorta was chronically dissected from an entry proximal to ruptured portion, to ascending aorta. Ascending aorta to aortic arch was replaced with 20 mm gelatin sealed graft under selective cerebral perfusion with hypothermia. Post-operatively tracheostomy was done because of respiratory failure, and there was some leak from distal anastomosis portion which was 42 mm in diameter at the operation. So replacement of descending thoracic aorta was performed using elephant trunk of the previously replaced graft. Post-reoperative course has been uneventful. She weaned from respiratory support. True aortic arch aneurysm combined with Stanford type A dissection is very rare. We presented ruptured true aortic arch aneurysm in association with Stanford type A chronic dissection which had an entry in true aneurysm.

Aged↗

PubMed1996

[Reoperation of a pseudoaneurysm eroding the sternum under hypothermic arrest of the brain through left thoracotomy].

Reoperation of a pseudo aneurysm eroding the sternum was carried out in a 76-year-old female, using partial cardiopulmonary bypass and hypothermic circulatory arrest of the brain through left thoracotomy. The pulsating aneurysm protruding over the sternum was about 3.5 x 3.5 cm in size. Therefore, median sternotomy was thought to be risky. Cardiopulmonary bypass was established with left atrium and pulmonary artery for venous cannulation and femoral artery for arterial one. The patient was cooled and then the bypass discontinued. Previous patcth of the aneurysm was partially splitting and new patch was sutured. She awaked without cerebral injury of the operative day. This technique can be used as one of an alternative surgical method in the treatment of the distal aortic arch aneurysms.

Aged↗

PubMed1996

[Immunosuppressive effect of intravenously injected docosahexaenoic acid on single lung allotransplantation in the rat].

Docosahexaenoic acid (DHA) is an omega 3 polyunsaturated fatty acid. The purpose of this study was to evaluate the immunosuppressive effect of intravenously injected DHA in rat orthotopically transplanted allograft lung. Based on the results of the post-operative treatment, the recipients were divided into four groups; Group A (n = 3): normal. Group B (n = 3): isotransplantation with no immunosuppressive drugs. Group C (n = 6): allotransplantation with no immunosuppressive drugs. Group D-1 (n = 3): allotransplantation with DHA at a dose of 0.5 g/kg/day x 2 at 0 and 3 post-operative days (POD). Group D-2 (n = 3): allotransplantation with DHA at a dose of 0.5 g/kg/day x 4 at 0, 1, 3 and 5 POD. Group D-3 (n = 6): allotransplantation with DHA at a dose of 0.5 g/kg/day x 4 at 0, 1, 2 and 3 POD. In Groups A and B, F344 rats were used as donor and recipient. In Groups C and D, F344 rats were used as recipient and WKAH rats as donor. Studies on morphology, bronchoalveolar lavage (BAL) and peripheral blood cells were performed at 7 POD after sacrifice. Histological changes in Group D-3 were milder than those in Grop C and D-1, but were more progressive than those in Groups A and B which showed no rejection. Peripheral leukocytes and polymorphonuclear leukocytes counts in Groups D-1, D-2, and D-3 were higher than those in Groups, A, B and C. Total cells and lymphocytes of BAL in Groups D-2 and D-3 were less than those in Group C, but total cells and polymorphonuclear leukocytes of BAL in Groups D-2 and D-3 were more than those in Groups A and B. This study suggested that intravenously injected DHA had an immunosuppressive effect on the allotransplanted lung in the rats.

Animals↗

PubMed1996

[Surgical outcome of aortic arch aneurysm in the institutes registered with Tokai Cardiovascular Surgeons Conference].

In aortic arch replacement, cerebral protection has been achieved by means of deep hypothermia associated with complete circulatory arrest, selective cerebral perfusion (SCP), or retrograde cerebral perfusion (RCP). We describe our results of the investigation with questionnaire to the institutes registered with the Tokai Cardiovascular Surgeons Conference in 1994. In 23 institute, surgical procedures of aortic arch were performed for 333 cases from 1989 to 1994, which were consisted of 126 cases of true atherosclerotic aneurysm and 206 cases of dissecting aneurysm. Cerebral disorders occurred in 11% (37/333). The incidence of cerebral disorders was significantly higher in patients with RCP methods (16%, 18/111), than SCP method (7%, 15/204, p < 0.05). In patients who had dissecting aneurysm, the incidence of cerebral disorders was 6% with SCP method (7/126) and 21% with RCP methods (14.66), respectively (p < 0.05). The cerebral disorders with RCP methods were most frequently caused by the malperfusion. In atherosclerotic cases, the causes of the cerebral disorders were mainly the embolic disorders.

Adult↗

PubMed1996

Evaluation of myocardial viability during simple cold storage with the use of electrical properties in broad frequencies.

BACKGROUND: The purpose of this study ws to determine whether myocardial viability during simple cold storage can be monitored from alteration of electrical properties of the preserved heart. METHODS: Twelve anesthetized dogs underwent rapid cardiac extirpation and were preserved in simple cold storage ( 4 degree C). They were divided into two groups according to preservation solutions. Groups S and U were preserved in saline and University of Wisconsin Solutions, respectively. The loss-tangent (Tan delta) in dielectric spectroscopy was analyzed on serial measurements of electrical properties of the preserved heart with an electrical impedance meter. Myocardial specimens were taken for myocardial adenosine triphosphate measurement with high-performance liquid chromatography and myocardial water content. We investigated the correlations among myocardial adenosine triphosphate, myocardial water content, and Tan delta. RESULTS: The maximum value of Tan delta corresponds to a frequency fT which ranged from 5 to 10 kHz in both groups and maximum Tan delta gradually decreased during preservation in both groups. Myocardial adenosine triphosphate in group U was significantly higher than that in group S. The ratio of measured adenosine triphosphate and maximum Tan delta to the preischemic values during preservation were expressed as percentage of adenosine triphosphate and percentage of maximum Tan delta. There was close correlation between myocardial percentage of adenosine triphosphate and percentage of maximum Tan delta during preservation in both groups. Myocardial water content in group S increased during preservation but did not increase in group U. There was no correlation between myocardial water content and percentage of maximum Tan delta during preservation. Tan delta function were used to characterize the electrical properties of biologic tissue and were clearly associated with ischemic histologic damage of tissues. CONCLUSIONS: Therefore measurement of electrical properties in broad frequencies of the preserved heart may be feasible as a monitor of graft viability in a minimally invasive method.

Adenosine↗

PubMed1996

Acoustic changes in voice after tonsillectomy.

UNLABELLED: The vocal tract from the glottis to the lips is considered to he a resonator and the voice is changeable depending upon the shape of the vocal tract. In this report, we examined the change in pharyngeal size and acoustic feature of voice after tonsillectomy. METHODS: Subjects were 20 patients. The distance between both anterior pillars (glossopalatine arches), and between both posterior pillars (pharyngopalatine arches) was measured weekly. For acoustic measurements, the five Japanese vowels and Japanese conversational sentences were recorded and analyzed. RESULTS: The distance between both anterior pillars became wider 2 weeks postoperatively, and tended to become narrower thereafter. The distance between both posterior pillars became wider even after 4 weeks postoperatively. No consistent changes in F0, F1 and F2 were found after surgery. Although there was a tendency for a decrease in F3, tonsillectomy did not appear to change the acoustical features of the Japanese vowels remarkably. It was assumed that the subject may adjust the shape of the vocal tract to produce consistent speech sounds after the surgery using auditory feedback.

Adult↗

PubMed1995

The role of endothelin and nitric oxide in modulation of normal and spastic cerebral vascular tone in the dog.

To investigate the roles of endothelin and nitric oxide (NO) in the regulation of cerebral vascular tone under basal conditions and in cerebral vasospasm following subarachnoid hemorrhage in dogs, we used BQ-123 (cyclo(-D-Trp-D-Asp-L-Pro-D-Val-L-Leu-) sodium salt), an endothelin ETA receptor antagonist, L-arginine, a substrate for the formation of NO, and NG-nitro-L-arginine methyl ester, an NO synthesis inhibitor, and measured the angiographic diameter of the basilar artery in vivo. In normal dogs, intracisternal (i.c.) injection of BQ-123 (0.6 mg/kg) produced a 29.4 +/- 6.11% (P < 0.01) increase in the basal diameter 24 h after injection. NG-nitro-L-arginine methyl ester (0.6 mg/kg i.c.) produced a 19.3 +/- 2.93% (P < 0.05) decrease in the basal diameter 2 h after injection. This decrease was significantly attenuated by both BQ-123 (0.06-0.6 mg/kg i.c.) and L-arginine (6 mg/kg i.c.), but not by D-arginine. In the two-hemorrhage canine model, BQ-123 significantly inhibited the development of cerebral vasospasm (36.9 +/- 4.11% decrease on day 5 and 42.0 +/- 4.54% decrease on day 6 in controls vs 21.7 +/- 4.75% decrease (P < 0.05) on day 5 and 20.8 +/- 4.14% decrease (P < 0.05) on day 6 for 0.6 mg/kg i.c.) significantly attenuated the cerebral vasospasm on day 4 from a mg/kg i.c.). Furthermore, in this model, L-arginine (6 30.9 +/- 5.78% decrease (before)) to a 12.6 +/- 5.99% decrease (after). The immunoreactive endothelin-1 levels in the endothelial layer and the adventitia of the basilar artery were much higher on days 3 and 7 after the injection of autologous blood than on day 0 before blood injection. These results suggest that endogenous endothelin and NO both participate in regulating the basal tone of cerebral arteries, and, therefore, the development of cerebral vasospasm following subarachnoid hemorrhage may be at least partially attributed to an impairment of the balanced action of endothelin and NO. Furthermore, endothelin ETA antagonists or NO products may be useful in the treatment of cerebral vasospasm following subarachnoid hemorrhage.

Amino Acid Sequence↗

PubMed1995

Pancreatic beta-cells in obesity. Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids.

To elucidate the mechanism of the basal hyperinsulinemia of obesity, we perfused pancreata from obese Zucker and lean Wistar rats with substimulatory concentrations of glucose. Insulin secretion at 4.2 and 5.6 mM glucose was approximately 10 times that of controls, whereas beta-cell volume fraction was increased only 4-fold and DNA per islet 3.5-fold. We therefore compared glucose usage at 1.4, 2.8, and 5.6 mM. Usage was 8-11.4 times greater in Zucker islets at 1.4 and 2.8 mM and 4 times greater at 5.6 mM; glucose oxidation at 2.8 and 5.6 mM glucose was > 12 times lean controls. To determine if the high free fatty acid (FFA) levels of obesity induce these abnormalities, normal Wistar islets were cultured with 0, 1, or 2 mM long chain FFA for 7 days. Compared to islets cultured without FFA insulin secretion by FFA-cultured islets (2 mM) perifused with 1.4, 3, or 5.6 mM glucose was increased more than 2-fold, bromodeoxyuridine incorporation was increased 3-fold, and glucose usage at 2.8 and 5.6 mM glucose was increased approximately 2-fold (1 mM FFA) and 3-fold (2 mM FFA). We conclude that hypersecretion of insulin by islets of obese Zucker fatty rats is associated with, and probably caused by, enhanced low Km glucose metabolism and beta-cell hyperplasia, abnormalities that can be induced in normal islets by increased FFA.

Animals↗

PubMed1995

Neurotransmitters partially restore glucose sensitivity of insulin and glucagon secretion from perfused streptozotocin-induced diabetic rat pancreas.

To elucidate the mechanisms of insensitivity of hormone secretion to glucose in streptozotocin-induced diabetic rat islets, we investigated the effects of acetylcholine (ACh) and norepinephrine on insulin and glucagon secretion in response to changes in glucose concentration, using perfused pancreas preparations. Basal insulin secretion at a blood glucose level of 5.6 mmol/l was significantly higher and basal glucagon secretion significantly lower in streptozotocin-induced diabetic rats than in controls, and neither high (16.7 mmol/l) nor low (1.4 mmol/l) blood glucose concentrations influenced insulin or glucagon secretion. Addition of 10(-6) mol/l ACh to the perfusate increased glucose-stimulated insulin secretion. Also, 10(-6) mol/l ACh, 10(-7) mol/l norepinephrine, as well as a combination of both, induced marked glucagon secretion, this was suppressed by high blood glucose level. Although simultaneous addition of 10(-6) mol/l ACh and 10(-7) mol/l norepinephrine induced only a slight increase in glucagon secretion in response to glucopenia, there was a significant increase in glucagon secretion in conjunction with an ambient decrease in insulin. Histopathological examination revealed a marked decline in acetylcholinesterase and monoamine-oxidase activities in the islets of streptozotocin-induced diabetic rats. We speculate that reduction of the potentiating effects of ACh and norepinephrine lessens glucose sensitivity of islet beta and alpha cells in this rat model of diabetes.

Acetylcholine↗

PubMed1995

Exogenous insulin dose-dependently suppresses glucopenia-induced glucagon secretion from perfused rat pancreas.

To clarify the role of insulin in modulating the glucagon response to glucose concentration changes, we investigated the effects of exogenous insulin (10 mU/mL, 100 mU/mL, and 3.3 U/mL) on responses to high glucose (5.6-->16.7 mmol/L), low glucose (5.6-->1.4 mmol/L), and arginine (10 mmol/L) stimulation using the perfused rat pancreas. Although glucagon levels were slightly suppressed by all of the exogenous insulin concentrations tested for the initial few minutes at 5.6 mmol/L glucose, baseline levels were maintained thereafter. Glucagon responses to high or normal glucose concentrations were not altered, but glucopenia-induced glucagon secretion was significantly suppressed as compared with that of controls (0.77 +/- 0.14 ng/min [10 mU/mL, n = 5], 0.55 +/- 0.14 ng/min [100 mU/mL, n = 5], 0.27 +/- 0.13 ng/min [3.3 U/mL, n = 5] v 1.38 +/- 0.20 ng/min [controls, n = 9], P < 0.05, respectively). The first phase of the glucagon response to arginine was potentiated (2.03 +/- 0.24 v 1.17 +/- 0.22 ng/min, P < .05) by 10 mU/mL exogenous insulin. The second phase of the glucagon response to arginine was significantly suppressed in the presence of higher concentrations of exogenous insulin (1.16 +/- 0.23 ng/min [100 mU/mL], 0.96 +/- 0.08 ng/min [3.3 U/mL] v 1.57 +/- 0.17 ng/min, P < .05, respectively). These results suggest that glucagon secretion is modified by the combined suppressive effects of glucose and insulin, although it is mainly glucose that mediates glucagon secretion in the physiological glucose range. Glucopenia- or arginine-induced glucagon secretion is suppressed by insulin.

Animals↗

PubMed1995

Adrenoceptor antagonists, but not guanethidine, reduce glucopenia-induced glucagon secretion from perfused rat pancreas.

This study was designed to investigate (1) whether norepinephrine is released in response to glucopenia in vitro, thereby stimulating glucagon secretion and, (2) the modulating effects of norepinephrine on insulin and glucagon secretion, using isolated perfused rat pancreas preparations. Simultaneous addition of the adrenergic receptor antagonists yohimbine, prazosin and propranolol, each at a concentration of 10-(5) mol/l, significantly potentiated glucose-stimulated insulin secretion (6.23 +/- 0.76 vs. 2.11 +/- 0.72 (control) nmol/min, P < 0.01), and suppressed glucopenia-induced glucagon secretion (0.59 +/- 0.10 vs. 1.34 + 0.18 (control) ng/min, P < 0.05). Also, 10-(5) mol/l yohimbine alone significantly potentiated glucose-stimulated insulin secretion (4.86 +/- 0.50 nmol/min, P < 0.05). The norepinephrine release inhibitor, guanethidine, significantly inhibited tyramine-induced secretion of both norepinephrine (7.86 +/- 0.77 vs. 49.7 +/- 2.3 nmol/min, P < 0.01) and glucagon (0.31 +/- 0.08 vs. 1.21 +/- 0.15 ng/min, P < 0.01), but exerted no effects on glucopenia-induced secretion of either norepinephrine or glucagon. We conclude that these results further support the concept that the neurotransmitter norepinephrine is released in response to glucopenia in vitro, and modulates insulin and glucagon secretion. Our data do not, however, provide evidence indicating that glucopenia-induced glucagon secretion is mainly mediated by activation of sympathetic nerve terminals around the alpha-cells in the isolated perfused rat pancreas.

Adrenergic Agents↗

PubMed1995

Prediction of pulmonary function after resection of primary lung cancer. Utility of inhalation-perfusion SPECT imaging.

To help determine whether preoperative perfusion and inhalation SPECT imagings are useful in predicting postoperative lung function, Tc-99m MAA perfusion SPECT imaging, CT scans, and pulmonary function tests were prospectively performed in 33 patients with primary lung cancer before and after lobectomy or pneumonectomy. Tc-99m Technegas inhalation SPECT imaging was performed in 6 of 33 patients as well. The authors also studied changes in radioactivity on the operated and nonoperated sides before and after surgery, examined the lowest limit value for adaptability to the operation, and made a comparison of both perfusion and inhalation SPECT imaging. The predicted postoperative values obtained from the preoperative Tc-99m MAA SPECT images correlated more closely with the measured 6-month postoperative values than with the measured 3-month postoperative values. The highest correlation coefficient (r = 0.86) was observed between the predicted forced vital capacity (FVC) value and the measured 6-month postoperative FVC value. In many cases, there was not a great difference between the 6-month and 3-month radioactivity on the operated side obtained from Tc-99m MAA SPECT images. This appears to indicate that pulmonary blood flow on the operated side has completely recovered by 3 months after surgery. However, radioactivity in both the upper and lower lobes of the nonoperated side increased soon after surgery compared with that before the operation, and had not returned to preoperative levels 6 months after surgery. The radioactivity in the right middle lobe did not change before and after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

PubMed1995

Defective insulin and glucagon secretion in isolated perfused pancreata of diabetic WBN/Kob rats.

To elucidate the pathophysiology of diabetes mellitus in male WBN/Kob rats, we performed pancreatic perfusion experiments and histopathological studies. Intraperitoneal glucose tolerance tests showed a diabetic pattern in 12-month-old WBN/Kob rats. In perfused pancreata of WBN/Kob rats, both the first and the second phases of insulin secretion in response to a 16.7 mM glucose challenge were markedly reduced compared with those in age-matched Wistar rats (p < 0.01, respectively). Furthermore, the insulin secretion rate in response to glucopenia (1.4 mM) was significantly higher (p < 0.05) and the decrement in insulin secretion was significantly lower (p < 0.05) in WBN/Kob rats. The decrement in glucagon secretion with 16.7 mM glucose was significantly blunted (p < 0.001), and the glucagon secretion rate in response to glucopenia was also significantly lower in WBN/Kob rats than in controls (p < 0.01). Although insulin secretion in response to 10 mM arginine was also moderately reduced in WBN/Kob rats (p < 0.05), the glucagon secretion rates in response to 10 mM arginine were similar in the two groups. Histopathological examination revealed widespread disappearance of acinar cells and islets, inflammatory changes, and marked fibrosis in the pancreata of WBN/Kob rats. Immunohistochemical studies showed decreased numbers of B cells in the islets of WBN/Kob rats. These findings suggest that this WBN/Kob rat strain is a useful model for studying not only pathogenesis, but also pathophysiology, i.e., defective hormonal secretion, in some types of human diabetes mellitus.

Animals↗

PubMed1995

Effects of D-phenylalanine-derivative hypoglycemic agent A-4166 on pancreatic alpha- and beta-cells: comparative study with glibenclamide.

We have reported that N-[(trans-4-isopropyl-cyclohexyl)-carbonyl]-D-phenylalanine (A-4166) stimulates insulin secretion in animal studies. To further elucidate the mechanisms underlying the actions of this agent, we investigated the effects of A-4166 on insulin and glucagon secretion with or without diazoxide, an ATP-sensitive potassium channel opener, using isolated perfused rat pancreas preparations, and compared the results with those of glibenclamide. Both 30 mumol/l A-4166 and 3 mumol/l glibenclamide significantly stimulated insulin secretion and reduced glucagon secretion to similar levels at a glucose concentration of 5.6 mmol/l (p < 0.01 for both vs. basal levels). After infusion of A-4166 was stopped, insulin levels promptly returned to the basal values, while insulin levels increased further even after discontinuation of glibenclamide. Furthermore, 100 mumol/l diazoxide significantly inhibited the insulin-stimulatory effects of both 30 mumol/l A-4166 and 3 mumol/l glibenclamide (p < 0.05 and p < 0.01, respectively). However, the effects of diazoxide on glucagon secretion differed between the two groups; 30 mumol/l A-4166 produced a transient increase in glucagon secretion (p < 0.05 vs. basal levels) but 3 mumol/l glibenclamide suppressed glucagon secretion further (p < 0.01 vs. without diazoxide) with concomitant administration of 100 mumol/l diazoxide. These findings suggest that A-4166 directly stimulates insulin secretion, at least in part, through mechanisms resembling those of sulfonylurea, but exerts different effect on glucagon secretion in isolated perfused rat pancreas.

Analysis of Variance↗