Biomedical subjects

A Kubota

Publications and source records attributed to A Kubota.

At least 37 records · Page 2Linked to original sources

PubMed2001

Evaluation of the peripheral visual field after foveal translocation.

PURPOSE: To evaluate the peripheral visual field after foveal translocation with scleral imbrication or 360-degree retinotomy. METHODS: Retrospective, single-center, nonrandomized study. We calculated the rate of preservation of the peripheral visual field using Goldmann perimetry by dividing the width of the postoperative V-4 isopter by the preoperative width and expressing the result as a percentage. RESULTS: In nine eyes that underwent scleral imbrication, the rate of preservation was 100.0% superiorly, 102.6% superotemporally, 99.9% temporally, 97.9% inferotemporally, 96.9% inferiorly, 82.3% inferonasally, 93.7% nasally, and 87.3% superonasally. In 33 eyes that underwent 360-degree retinotomy, it was 89.1%, 87.0%, 81.9%, 78.1%, 86.6%, 90.0%, 89.9%, and 86.8%, respectively. CONCLUSION: After foveal translocation with scleral imbrication, the peripheral visual field was preserved except for slight narrowing nasally; 360-degree retinotomy resulted in preservation of the visual field, except for slight narrowing in all meridians.

Aged↗

PubMed2001

Comparison of three techniques of foveal translocation in patients with subfoveal choroidal neovascularization resulting from age-related macular degeneration.

PURPOSE: To report the results of three methods of foveal translocation in the presence of subfoveal choroidal neovascular membrane resulting from age-related macular degeneration. METHODS: We treated 51 eyes of 51 consecutive patients with subfoveal choroidal neovascular membranes resulting from age-related macular degeneration with one of three techniques of foveal translocation surgery: foveal translocation with partial retinotomy (n = 6), limited translocation (n = 9), and translocation with 360-degree retinotomy (n = 36). All patients were followed for at least 6 months postoperatively. The size of the choroidal neovascular membrane and the amount of foveal displacement, the best-corrected visual acuity, and complications were recorded preoperatively and postoperatively. RESULTS: The mean distance of the foveal translocation was greater in the 360-degree retinotomy group (3340 microm) than in the partial retinotomy (1060 microm, P <.001) and the limited translocation groups (1120 microm, P <.001). A final visual acuity of 20/200 or better was achieved in two eyes (33%) in the partial retinotomy group, seven eyes (78%) in the limited translocation group, and 23 eyes (64%) in the 360-degree retinotomy group. The final visual acuity improved by 0.2 logarithm of minimal angle of resolution (logMAR) unit or more in one eye (17%), one eye (11%), and seven eyes (19%), respectively. The final visual acuity was maintained within 1 line in zero eyes, five eyes (56%), and 19 eyes (53%), respectively. A retinal detachment developed postoperatively in five eyes (83%), zero eyes (0%), and 15 eyes (42%), respectively. CONCLUSIONS: A significant number of patients improved or maintained best-corrected visual acuity after translocation with 360-degree retinotomy, and limited translocation, whereas translocation with 360-degree retinotomy is suitable for larger choroidal neovascular membranes because it resulted in the greatest foveal displacement among the three translocation procedures.

Aged↗

PubMed2001

Non-Hodgkin's malignant lymphoma of the sinonasal tract--treatment outcome for 53 patients according to REAL classification.

OBJECTIVE: Although the Working Formulation is commonly used to classify NHL in Japan, it has been recognized as imperfect for primary extranodal lymphoma, especially for patients with sinonasal disease because of their histological characteristics. The present study investigated the clinical characteristics and the prognosis of sinonasal lymphomas according to REAL classification. METHODS: Fifty-three patients with non-Hodgkin's malignant lymphoma (NHL) of the sinonasal tract were treated between 1981 and 1997. The age at clinical presentation was from 10 to 84 years (mean, 52.4 years). According to the Ann Arbor system, there were 30 patients with Stage IE, 13 with Stage IIE, 4 with Stage IIIE, and 6 with Stage IVE lymphomas. Twenty-two patients (41.5%) had B symptoms. The primary sites were the nasal cavity (67.8%), maxillary sinus (20.8%), ethmoidal sinus (9.4%), and frontal sinus (1.9%). The survival data was calculated by Kaplan-Meier method. Statistical analysis was performed with a generalized Wilcoxon method. RESULTS: All of the lymphomas showed a diffuse growth pattern. Based on the origin of the tumor cells, the authors classified NHL of the sinonasal tract into five groups with the REAL classification of Japan: diffuse large B-cell lymphoma (22.6%), peripheral T-cell lymphomas (15.1%), angiocentric lymphoma (35.9%), other lymphomas and unclassified types. Of 53 patients, 39 (73.6%) received chemotherapy and radiotherapy, eight patients received chemotherapy alone, and four patients received radiotherapy alone. The cumulative 5-year survival rates were 28.5% for all of the types, 55.0% for diffuse large B-cell lymphoma, 33.3% for peripheral T-cell lymphoma, and 19.7% for angiocentric lymphoma. Results suggest that conventional combined treatment (CHOP chemotherapy+radiotherapy) is ineffective for NHL of the sinonasal tract, and especially so for NHL in the nasal cavity, NHL with tumor cells with positive T-cell markers, NHL further than Stage IIE and NHL with B symptoms. CONCLUSION: (1) In light of this ineffectiveness, new therapies must be developed to improve patient outcome instead of the conventional combined treatment; (2) REAL classification is clear and useful for sinonasal lymphomas in Japan.

Adolescent↗

PubMed2001

Feline ubiquitin fusion protein genes.

Using cDNA from a CRFK cell line as a template, PCR amplification was performed with the Ub1S and poly(dT) primers to isolate feline ubiquitin genes. Sequencing of the 495 bp PCR fragment revealed that the putative amino acids induced by this fragment gave a fusion protein consisting of a ubiquitin polypeptide (76 amino acids) and an extension protein of ribosomal proteins L40 (52 amino acids). The putative amino acid sequence of ubiquitin was identical to those of humans, rats and pigs. The recombinant glutathione S-transferase (GST)-feline ubiquitin fusion proteins were produced in Escherichia coli and purified. The fusion proteins had a molecular weight of about 42 kDa and were detected by immunoblot assay with rabbit anti-ubiquitin antiserum. The mRNAs from heat-shocked and non-heat-shocked cells were subjected to RT-PCR (Ub1S and poly(dT) primers) analysis. The molecular weights of the ubiquitinated proteins in heat-shocked CFRK cells were between 18 kDa and 24 kDa by immunoblot assay. These results suggested that there were more ubiquinated proteins in the heat-shocked CRFK cells than in the pre-heat-shocked cells.

Amino Acid Sequence↗

PubMed2001

Effect of meropenem on disposition kinetics of valproate and its metabolites in rabbits.

PURPOSE: We investigated the effect of meropenem (MEPM) on the disposition kinetics of valproate (VPA) and its metabolites in rabbits. METHODS: Rabbits were given 75 mg/kg VPA intravenously with or without 300 mg/kg MEPM. RESULTS: The plamsa total clearance of VPA was significantly increased to about 1.5 times the control (6.09 mL/min/kg vs. 4.28 mL/min/kg) by MEPM (P < 0.05). The values of the area under the plasma concentration-time curve (AUC) of 2-en-VPA, a product of beta-oxidation, and VPA-glucuronide (VPA-G) were significantly decreased to about 55% and 78% of the control, respectively (P < 0.05). The cumulative urinary excretions of VPA in the control and MEPM-treated groups were 0.54% and 0.62% of the dose, respectively, whereas those of VPA-G were 45.6% and 62.5%, respectively. The urinary excretion of VPA-G was significantly increased by MEPM (P < 0.05). Further, in the case of 33.8 mg/kg VPA-G administered intravenously the AUC value of VPA-G was unchanged by MEPM, whereas that of the generated VPA was significantly decreased to about half of the control. CONCLUSIONS: The increase of the total clearance of VPA caused by MEPM appears to be a consequence of increased renal clearance of VPA-G, as well as suppression of VPA-G hydrolysis in the liver.

Animals↗

PubMed2001

An autopsy case of pancreatic and ectopic nesidioblastosis.

We report an autopsy case of pancreatic and ectopic nesidioblastosis. A five-month-old Japanese girl was born at 35 weeks gestation, and showed clinical symptoms of hyper-insulinemic hypoglycemia before death. At autopsy a tumorous nodule was observed at the portion of the jejunum, 90 cm from Treitz's ligament. The nodule measured 30 x 20 x 20 mm. The ectopic pancreas, also revealed nesidioblastosis histologically. Immunohistologically, both nesidioblastoses were stained positive for chromogranin A, insulin, glucagon and somatostatin. The proliferating cell nuclear antigen (PCNA) and Ki-67 indices were less than 4% in the nesidioblastosis. To our knowledge, this is the first reported case of nesidioblastosis demonstrating proliferating activity with PCNA and Ki-67, and is the third reported case of nesidioblastosis arising in the pancreas and ectopic pancreas.

Choristoma↗

PubMed2001

Increased expression of cyclooxygenase-2 in human salivary gland tumors.

We examined the immunohistochemical localization of cyclooxygenase (COX)-2 in human salivary gland tumors. Thirty salivary gland adenomas (SGA), 40 salivary gland carcinomas (SGC) and 15 normal salivary glands (NSG) were studied. NSG showed restricted COX-2 staining only in the epithelial cells of salivary ducts. In contrast, COX-2 protein was detected in 27 cases of SGA (90%), except for three myoepitheliomas, and in all cases of SGC (100%) at various intensities and in various fashions. Thirteen SGA (43%) and 36 SGC (90%) cases showed strong COX-2 staining predominantly in tumor cells containing ductal components, as did serous and mucous acinic components of acinic cell carcinomas, mucoepidermoid carcinomas and mucinous carcinomas. These findings may suggest that COX-2 in salivary gland tumors is expressed in tumor cells derived from pluripotential ductal epithelium that can histologically develop into either serous or mucinous acinar cells.

Adenoma↗

PubMed2001

Operative management for sacrococcygeal teratoma diagnosed in utero.

BACKGROUND/PURPOSE: Sacrococcygeal teratomas (SCT) diagnosed in utero have been reported to be large and associated with high perinatal mortality rate. However, operative management including timing of operation after birth, combined abdominal approach for devascularization, and the position of the patients during resection is not well established. METHODS: A retrospective review of 14 patients with SCT between 1978 and 1999 was performed. To prevent massive bleeding during surgery, the authors used an abdominoperineal resection in the supine position after devascularization. The patients' clinical and sonographic characteristics, prenatal outcome, operative management, and postnatal outcomes were examined. RESULTS: One fetus died in utero. Two patients died within a week, but no late death and no malignant degeneration were noted. A staged operation with devascularization was performed in 2 patients, and 1 death occurred. Surgical management was analyzed between survivors without massive bleeding at surgery (n = 9) and others (n = 4). A significant difference was observed in the subgroup of tumor resection with devascularization or supine position and that of early resection with devascularization or supine position. CONCLUSIONS: Early resection using the abdominoperineal approach supported by close antenatal sonography may be preferable for a favorable outcome. Resection in the supine position after devascularization may have advantages of respiratory management, cardiac resuscitation, and bleeding prevention. J Pediatr Surg 36:545-548.

Female↗

PubMed2001

Clinicopathologic relationship of hypoganglionosis.

BACKGROUND/PURPOSE: Congenital motor dysfunction of the intestine associated with a morphologically abnormal myenteric nervous plexus (MP) is known as Hirschsprung's disease allied disorder (HAD). However, the clinicopathologic features of HAD are not well understood, partially because a standardized method of histologic evaluation of MP has not been established. To elucidate the clinicopathologic relationship of HAD the authors reviewed 6 cases of HAD using a newly devised histologic evaluation method. METHODS: Flat-mounted frozen sections of the ileum were stained for S-100 protein by fluorescent immunohistochemistry. Quantitative evaluation of MP was performed by measuring the fluorescence-positive area (MP ratio), and the results were compared with those of age-matched normal controls. RESULTS: All of 6 patients required laparotomy within 1 month after birth and enterostomy between 23 days and 10 months. Three died of intractable enteritis by the age of 2.2 years and were totally dependent on parenteral nutrition (PN) throughout their lives. The other 3 have survived for 6 to 10 years but have required PN occasionally. MP ratio in controls was more than 0.34 at all ages, whereas that in HAD was significantly lower than that in controls according to the clinical severity. CONCLUSION: MP size measured on 2-dimensional demonstration is suggested to be an indicator of clinical severity of HAD. J Pediatr Surg 36:898-900.

Case-Control Studies↗

PubMed2001

Motor abnormality in the gastroduodenal junction in patients with infantile hypertrophic pyloric stenosis.

BACKGROUND/PURPOSE: Periodic clusters of phasic pressure waves in the gastroduodenal junction (GDJ) have been seen in patients with infantile hypertrophic pyloric stenosis (IHPS). This study investigated the details of these pressure waves in relation to disturbed transpyloric flow in IHPS. METHODS: Manometric study was performed in 11 IHPS patients before and after atropine therapy and 2 non-IHPS infants. Pressure changes in the GDJ were measured with an 8-channel sleeve or a 9-channel sidehole micromanometric assembly under fluoroscopic control for 2 hours. RESULTS: Clusters of phasic pressure waves (365 +/- 42 mm Hg) associated with an increase in basal pressure (10 +/- 3 mm Hg) were intermittently observed in the GDJ in all IHPS patients. Similar observations were not made in the non-IHPS infants. Most antral pressure waves occurred simultaneously with those pressure waves in the GDJ in the IHPS patients. Atropine (0.01 mg/kg) transiently abolished the phasic and tonic pressure waves for 19 +/- 10 minutes. Significantly fewer phasic pressure waves were observed after atropine therapy. CONCLUSIONS: Characteristic phasic and tonic contractile activity in the GDJ is uncoordinated with the antral contractions in IHPS patients. Such incoordination may be an important factor in the disturbed transpyloric flow in IHPS.

Atropine↗

PubMed2001

Clinical characteristics of congenital esophageal stenosis distal to associated esophageal atresia.

BACKGROUND: Congenital esophageal stenosis (CES) has been reported to be a rare association in patients with esophageal atresia or tracheoesophageal fistula, or both (EA-TEF). This study investigates the clinical characteristics of this association with special reference to its treatment. METHODS: A retrospective review of medical and radiographic records of 81 patients who underwent primary repair of EA-TEF was performed. An association of CES was diagnosed when they showed histologic evidence or persistent radiographic images of esophageal narrowing since the neonatal period. RESULTS: Eleven of 81 EA-TEF patients (14%) were identified with CES. Their symptoms were difficulty in swallowing solid food, food impaction, emesis, stridor, repeated respiratory infection, and failure to thrive. Two patients had a recurrence of TEF. Three patients were diagnosed with CES in the neonatal period-2 at the time of primary repair of EA-TEF and 1 on the initial postoperative esophagram. The remaining 8 patients were diagnosed between the ages of 2 months and 3 years. Although esophageal dilatation was attempted in 9 patients, its effectiveness was temporary in all except 2 patients and esophageal laceration occurred in 4 patients. Surgical repair including myotomy and resection of the narrow segment was performed in 7 patients, in 6 of whom Nissen/Collis-Nissen fundoplication was added. A histologic examination was performed in 5 patients, revealing that their CES was due to fibro-muscular hypertrophy (2) or tracheobronchial remnants (3). The long-term outcome was satisfactory in all patients except one who showed wrap herniation. CONCLUSIONS: The association between CES and EA-TEF is not rare. Esophageal dilatation was not universally effective and carried with it a considerable incidence of esophageal leakage. An antireflux operation concomitant with repair of CES may be useful to prevent postoperative gastroesophageal reflux in patients with a narrowing close to the esophagogastric junction.

Child, Preschool↗

PubMed2001

The non-classical MHC class I molecule Qa-1(b) inhibits classical MHC class I-restricted cytotoxicity of cytotoxic T lymphocytes.

The CD94/NKG2A heterodimer is an inhibitory receptor expressed on a subset of mouse NK cells. CD94/NKG2A recognizes the non-classical MHC class I (class Ib) molecule Qa-1(b) and inhibits NK cytotoxicity. Qa-1(b) presents a peptide derived from the leader sequence of classical MHC class I molecules. Here, we examined the role of CD94/NKG2A in T cell-mediated cytotoxicity. Soluble tetrameric Qa-1(b) bound to almost all CD8(+), but not CD4(+), T cells. This binding seems to be mediated by CD8, because COS cells transfected with CD8 also bound Qa-1(b) tetramer. Therefore, the expression of CD94/NKG2 in T cells was further examined by single-cell RT-PCR. Most murine CD8(+) T cells constitutively expressed CD94 and NKG2A transcripts, whereas they were not detected in CD4(+) T cells. Co-expression of Qa-1(b) and D(k) on target cells significantly inhibited cytotoxicity of D(k)-specific cytotoxic T lymphocytes generated by mixed lymphocyte reaction, indicating that Qa-1(b) on antigen-presenting cells interacts with CD94/NKG2A on CD8 T cells and regulates classical MHC class I-restricted cytotoxic T cells. These results suggest a significant role of CD94/NKG2A as an inhibitory receptor on CD8(+) T cells.

Animals↗

PubMed2001

Human TSC-22 gene: no association with type 2 diabetes.

OBJECTIVE: In order to elucidate whether or not genetic variations of TSC-22 (TGF [transforming growth factor]-beta-stimulated clone 22), which was originally identified as a TGF-beta-responsive leucine zipper protein in murine osteoblastic cells, are associated with type 2 diabetes, the genomic organization of the human TSC-22 gene was determined and the association between its polymorphisms and type 2 diabetes was examined. RESULTS: The human TSC-22 gene spans approximately 5 kilobase pairs and is encoded in three exons. Two single nucleotide polymorphisms (SNPs) were identified in the coding region of the first exon, two other SNPs in the first intron, and one SNP in the putative promoter region. There were, however, no significant differences in the frequency of these polymorphisms between patients with type 2 diabetes and non-diabetic control subjects. CONCLUSION: It is unlikely that the TSC-22 gene is a locus responsible for type 2 diabetes.

Aged↗

PubMed2001

Laparoscopic ovarian cystectomy using a single umbilical puncture method.

To establish a minimally invasive technique to perform ovarian cystectomy, the authors applied a single umbilical puncture method. A 2-month old female infant was admitted to the hospital because of an ovarian cyst that showed no spontaneous shrinkage after her birth. An umbilical semicircular incision was made to insert a 10-mm trocar, into which a 3-mm laparoscope was inserted. The ovarian cyst was grasped using forceps inserted through an operating channel of the scope, and the cyst was removed through the incision. After aspiration of the cyst, the free cyst wall was resected, leaving the intact ovarian tissue. The operation was performed without difficulty or complication. The postoperative course was uneventful. The wound was inconspicuous, and the result was cosmetically excellent. The case demonstrated the feasibility of the minimally invasive technique using a single umbilical puncture for ovarian cystectomy in an infant.

Female↗

PubMed2000

Increased expression of c-erbB-3 protein and proliferating cell nuclear antigen during development of verrucous carcinoma of the oral mucosa.

BACKGROUND: The roles of c-erbB-3 gene and protein in the pathogenesis, progression, and outcome of oral carcinoma remain unknown. To determine whether c-erbB-3 expression could serve as an indicator of progression from premalignant to malignant transformation and of prognoses in patients with oral carcinoma, the authors examined the relation between the expression of c-erbB-3 protein and cell proliferation activity during the development of oral verrucous carcinoma (VC). METHODS: Immunohistochemical techniques were used to evaluate c-erbB-3 protein and proliferative cell nuclear antigen (PCNA). Sixty-one samples (36 patients) of verrucous hyperplasia (VH), VC, and well differentiated squamous cell carcinoma arising from verrucous carcinoma (V-WSCC) in the oral mucosa were examined. RESULTS: Normal human oral mucosa showed weak c-erbB-3 immunostaining, predominantly on the epithelial surface. In contrast, 7 (39%) of 18 VHs, 25 (84%) of 31 VCs, and all (100%) of 12 V-WSCCs demonstrated overexpression of c-erbB-3 protein with increased expression of PCNA in some premalignant epithelial cells and many tumor cells. This finding suggested the involvement of c-erbB-3 gene in the progression from VH to VC and V-WSCC. CONCLUSIONS: Overexpression of c-erbB-3 protein correlated with increased PCNA labeling index, indicating that c-erbB-3 may contribute to malignant transformation and tumor growth. Further, patients with high expression of both c-erbB-3 and PCNA had a poor outcome. Study results suggested that c-erbB-3 expression was an index of malignancy during progression from VH to VC and V-WSCC and might have been involved in the outcome of oral carcinoma patients.

Carcinoma, Verrucous↗

PubMed2000

Sustained enhancement of Ca(2+) influx by glibenclamide induces apoptosis in RINm5F cells.

Cytosolic Ca(2+) elevations are known to be involved in triggering apoptosis in many tissues, but the effect of sustained enhancement of Ca(2+) influx on apoptosis in beta cells remains unknown. We have found that the viability of RINm5F cells is decreased dose-dependently by continuous exposure to glibenclamide at concentrations from 10(-7) to 10(-4) M, and that this effect is partially ameliorated by pretreatment with cycloheximide. Electrophoresis of the cells exposed to glibenclamide revealed ladder-like fragmentation characteristic of apoptosis, and which also is suppressed by cycloheximide pretreatment. By using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, we detected increased DNA fragmentation in the nuclei of the cells exposed to glibenclamide, and staining with Hoechst 33342 and propidium iodide showed a dose-dependent increase in the number of cells with the chromatin condensation and fragmentation in their nuclei that is characteristic of apoptosis. The effects of glibenclamide on cell viability and apoptotic cell death were partially inhibited by treatment with Ca(2+) channel blocker, and by reducing the extracellular Ca(2+) concentration during glibenclamide exposure, suggesting that they may be derived from increased Ca(2+) influx. Furthermore, only the percentage of apoptotic cells, and not that of necrotic cells, increased with the increasing intracellular Ca(2+) concentration during glibenclamide exposure. In conclusion, we have demonstrated that the sustained enhancement of Ca(2+) influx caused by glibenclamide exposure can induce apoptotic cell death in a pure beta cell line.

Animals↗

PubMed2000

Antioxidant alpha-tocopherol ameliorates glycemic control of GK rats, a model of type 2 diabetes.

We have shown recently that oxidative stress by chronic hyperglycemia damages the pancreatic beta-cells of GK rats, a model of non-obese type 2 diabetes, which may worsen diabetic condition and suggested the administration of antioxidants as a supportive therapy. To determine if natural antioxidant alpha-tocopherol (vitamin E) has beneficial effects on the glycemic control of type 2 diabetes, GK rats were fed a diet containing 0, 20 or 500 mg/kg diet alpha-tocopherol. Intraperitoneal glucose tolerance test revealed a significant increment of insulin secretion at 30 min and a significant decrement of blood glucose levels at 30 and 120 min after glucose loading in the GK rats fed with high alpha-tocopherol diet. The levels of glycated hemoglobin A1c, an indicator of glycemic control, were also reduced. Vitamin E supplementation clearly ameliorated diabetic control of GK rats, suggesting the importance of not only dietary supplementation of natural antioxidants but also other antioxidative intervention as a supportive therapy of type 2 diabetic patients.

Animals↗

PubMed2000

Wortmannin, a PI3-kinase inhibitor: promoting effect on insulin secretion from pancreatic beta cells through a cAMP-dependent pathway.

To determine the role of phosphatidylinositol 3-kinase (PI3-kinase) in the regulation of insulin secretion, we examined the effect of wortmannin, a PI3-kinase inhibitor, on insulin secretion using the isolated perfused rat pancreas and freshly isolated islets. In the perfused pancreas, 10(-8) M wortmannin significantly enhanced the insulin secretion induced by the combination of 8.3 mM glucose and 10(-5) M forskolin. In isolated islets, cyclic AMP (cAMP) content was significantly increased by wortmannin in the presence of 3.3 mM, 8.3 mM, and 16.7 mM glucose with or without forskolin. In the presence of 16.7 mM glucose with or without forskolin, wortmannin promoted insulin secretion significantly. On the other hand, in the presence of 8.3 mM glucose with forskolin, wortmannin augmented insulin secretion significantly; although wortmannin tended to promote insulin secretion in the presence of glucose alone, it was not significant. To determine if wortmannin increases cAMP content by promoting cAMP production or by inhibiting cAMP reduction, we examined the effects of wortmannin on 10(-4) M 3-isobutyl-1-methylxantine (IBMX)-induced insulin secretion and cAMP content. In contrast to the effect on forskolin-induced secretion, wortmannin had no effect on IBMX-induced insulin secretion or cAMP content. Moreover, wortmannin had no effect on nonhydrolyzable cAMP analog-induced insulin secretion in the perfusion study. These data indicate that wortmannin induces insulin secretion by inhibiting phosphodiesterase to increase cAMP content, and suggest that PI3-kinase inhibits insulin secretion by activating phosphodiesterase to reduce cAMP content.

1-Methyl-3-isobutylxanthine↗