Re-examination of passives and related aspects in Japanese syntax.

The passive construction has played an important role, in different ways, in various types of grammatical framework. It has motivated Chomsky to introduce transformations and the basic concept of the deep and surface structures. It has also contributed to the foundation of Relational Grammar and to that of Bresnan's realistic model (1978). In the literature of Japanese linguistics the passive construction is also one of the topics that has been discussed to a great extent. There have been two major contrasting theories proposed for Japanese passives within the standard transformational framework: Uniform and Nonuniform Theory. The main aim of this thesis is to propose a theory which can account for more facts about Japanese passives than those above. Revised Uniform Theory (R.U.T.) is introduced for this purpose. The proposal of a theory such as R.U.T. is not totally new in respect of the deep structure of passives, since Inoue (1976) has proposed a comparable theory in this respect. However, in this thesis a different passive rule is argued for with a correspondingly different analysis of the surface structure from Inoue's. In particular it is shown that certain passive sentences cannot be accounted for by the rule based on Inoue's (or by any other rule which derives a passive subject solely from an object of an active sentence in one way or another). As a result Passive- Raising is proposed. In the course of the discussion, it is shown that it is necessary to incorporate the interpretive approach of adverbs into the Extended Standard Theory. The rules are designed to apply according to Pullum's (1976) notion of the Universally Determined Rule Application principle. Two arguments concerning passives (by Kuroda 1965 and by Kuno 1976) are then re-considered from the point of view of R.U.T. In addition, the causative construction is discussed in relation to passives and Chomsky's (1973/ 75/76) conditions on transformations are examined on the basis of Passive-Raising. It is shown that his conditions do not hold in Japanese

Identification of the matricellular protein Fibulin-5 as a target molecule of glucokinase-mediated calcineurin/NFAT signaling in pancreatic islets

Glucokinase-mediated glucose signaling induces insulin secretion, proliferation, and apoptosis in pancreatic β-cells. However, the precise molecular mechanisms underlying these processes are not clearly understood. Here, we demonstrated that glucokinase activation using a glucokinase activator (GKA) significantly upregulated the expression of Fibulin-5 (Fbln5), a matricellular protein involved in matrix-cell signaling, in isolated mouse islets. The islet Fbln5 expression was induced by ambient glucose in a time- and dose-dependent manner and further enhanced by high-fat diet or the deletion of insulin receptor substrate 2 (IRS-2), whereas the GKA-induced increase in Fbln5 expression was diminished in Irs-2-deficient islets. GKA-induced Fbln5 upregulation in the islets was blunted by a glucokinase inhibitor, KATP channel opener, Ca2+ channel blocker and calcineurin inhibitor, while it was augmented by harmine, a dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) 1 A inhibitor. Although deletion of Fbln5 in mice had no significant effects on the glucose tolerance or β-cell functions, adenovirus-mediated Fbln5 overexpression increased glucose-stimulated insulin secretion in INS-1 rat insulinoma cells. Since the islet Fbln5 expression is regulated through a glucokinase/KATP channel/calcineurin/nuclear factor of activated T cells (NFAT) pathway crucial for the maintenance of β-cell functions, further investigation of Fbln5 functions in the islets is warranted

Advantage of Insulin Glulisine Over Regular Insulin in Patients With Type 2 Diabetes and Severe Renal Insufficiency

ObjectivesTo compare the efficacy and safety of insulin glulisine over regular insulin in patients with type 2 diabetes and severe renal insufficiency.SubjectsOur study included 18 patients with type 2 diabetes and a mean (range) estimated glomerular filtration rate of 13.2 mL/minute/1.73 m2 (5.8-27.6), which corresponds to stage 4-5 chronic kidney disease.DesignAfter titration of doses, regular insulin was administered thrice daily on Day 1, along with continuous glucose monitoring for 24 h starting at 7 am. Exactly equal doses of insulin glulisine were administered on Day 2. Area under the curve (AUC) for blood glucose level variation after breakfast (AUC-B 0-4), lunch (AUC-L 0-6), and dinner (AUC-D 0-6) were evaluated.ResultsAUC-B 0-4 and AUC-D 0-6 were significantly lower with insulin glulisine than with regular insulin (AUC-B 0-4: 3.3 ± 4.7 vs. 6.2 ± 5.4 × 102 mmol/L·minute, respectively, P = .028; AUC-D 0-6: 1.8 ± 7.3 vs. 6.5 ± 6.2 × 102 mmol/L·minute, respectively, P = .023). In contrast, AUC-L 0-6 was higher with insulin glulisine than with regular insulin (AUC-L 0-6: 7.6 ± 6.4 vs. 4.2 ± 8.7 × 102 mmol/L·minute, respectively, P = .099), suggesting a prolonged hypoglycemic action of regular insulin after lunch.ConclusionsInsulin glulisine effectively suppressed postprandial hyperglycemia, whereas regular insulin caused a prolonged hypoglycemic action. These findings support the effectiveness and safety of insulin glulisine in patients with type 2 diabetes and severe renal insufficiency