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Yuichiro Yamada

Publications and source records attributed to Yuichiro Yamada.

65 records · Page 4Linked to original sources
PubMed2002

Inhibition of gastric inhibitory polypeptide signaling prevents obesity.

Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat. Here we describe a novel pathway of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with insulin resistance. In contrast, mice lacking the GIP receptor (Gipr(-/-)) fed a high-fat diet were clearly protected from both the obesity and the insulin resistance. Moreover, double-homozygous mice (Gipr(-/-), Lep(ob)/Lep(ob)) generated by crossbreeding Gipr(-/-) and obese ob/ob (Lep(ob)/Lep(ob)) mice gained less weight and had lower adiposity than Lep(ob)/Lep(ob) mice. The Gipr(-/-) mice had a lower respiratory quotient and used fat as the preferred energy substrate, and were thus resistant to obesity. Therefore, GIP directly links overnutrition to obesity and it is a potential target for anti-obesity drugs.

Adipose Tissue↗
PubMed2002

Treatment of streptozotocin-induced diabetes mellitus by transplantation of islet cells plus bone marrow cells via portal vein in rats.

BACKGROUND: We have established a new method for the transplantation of allogeneic pancreatic islets (PIs) using sublethal irradiation (9 Gy) plus simultaneous transplantation of PIs and bone marrow cells (BMCs) via the portal vein (PV) followed by intravenous (i.v.) injection of donor BMCs (9 Gy + PV + i.v.). METHODS: Approximately 600 PIs of Brown Norway (BN: RT1An, RT1Bn) rats were transplanted into the liver of streptozotocin-induced diabetic Fischer 344 (F344: RT1Al, RT1Bl) rats via the PV. BMCs (3x108) of BN rats were injected via the PV or i.v. into the recipients simultaneously. In some groups, additional i.v. injections of BMCs from BN rats were given 5 days after the PI transplantation. RESULTS: All the recipients (10 of 10) in the 9 Gy + PV + i.v. group showed normoglycemia for more than 1 year, whereas PIs were rejected within 30 days after transplantation in the group of 9 Gy + i.v. + i.v. CONCLUSIONS: These results suggest that simultaneous transplantation of PIs and BMCs via the PV is effective in inducing persistent tolerance.

Animals↗
PubMed2002

Mutation analysis in PKD1 of Japanese autosomal dominant polycystic kidney disease patients.

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal disorder (incidence, 1:1,000). The mutation of PKD1 is thought to account for 85% of ADPKD. Although a considerable number of studies on PKD1 mutation have been published recently, most of them concern Caucasian ADPKD patients. In the present study, we examined PKD1 mutations in Japanese ADPKD patients. Long-range polymerase chain reaction (LR-PCR) with PKD1-specific primers followed by nested PCR was used to analyze the duplicated region of PKD1. Six novel chain-terminating mutations were detected: three nonsense mutations (Q2014X transition in exon 15, Q2969X in exon 24, and E2810X in exon 23), two deletions (2132del29 in exon10 and 7024delAC in exon 15), and one splicing mutation (IVS21-2delAG). There was also one nonconservative missense mutation (T2083I). Two other potentially pathogenic missense mutations (G2814R and L2816P) were on the downstream site of one nonsense mutation. These three mutations and a following polymorphism (8662C>T) were probably the result of gene conversion from one of the homologous genes to PKD1. Six other polymorphisms were found. Most PKD1 mutations in Japanese ADPKD patients were novel and definitely pathogenic. One pedigree did not link to either PKD1 or PKD2.

Adolescent↗
PubMed2002

C-reactive protein and insulin resistance in non-obese Japanese type 2 diabetic patients.

The aim of the present study was to investigate the relationship between C-reactive protein (CRP) and insulin resistance in non-obese Japanese type 2 diabetic patients. A total of 135 non-obese Japanese type 2 diabetic patients (96 men and 39 women, aged 36 to 83 years, with a body mass index [BMI] of 16.2 to 26.8 kg/m2) were studied. BMI, glycosylated hemoglobin (HbA(1c)), fasting concentrations of plasma glucose, serum lipids (triglycerides, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol, and total cholesterol), CRP, and fibrinogen were measured. LDL cholesterol was calculated using the Friedewald formula. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Univariate regression analysis showed that CRP value was positively correlated to age (r = 0.218, P =.012), BMI (r = 0.239, P =.006), HOMA-IR (r = 0.397, P <.0001), triglycerides (r= 0.310, P <.005), LDL cholesterol (r= 0.179, P =.038), and fibrinogen (r = 0.371, P <.0001) levels and inversely correlated to HDL cholesterol (r = 0.174, P =.044) level in our diabetic patients. Multiple regression analysis showed that CRP was independently predicted by HOMA-IR (P<.0001, F = 11.6) and fibrinogen (P<.0001, F = 34.2), which explained 23.5% of the variability of CRP in our non-obese Japanese type 2 diabetic patients. These results indicate that insulin resistance and fibrinogen level are independent predictors of CRP in non-obese Japanese type 2 diabetic patients.

Asian People↗
PubMed2002

Effect of high dietary fat on insulin secretion in genetically diabetic Goto-Kakizaki rats.

INTRODUCTION AND AIM: To clarify the effects of a high fat-diet on insulin secretion from genetically diabetic beta cells, Goto-Kakizaki rats and Wistar rats were subjected to oral glucose tolerance test (OGTT) after 12-week high-fat feeding. METHODOLOGY: We compared Wistar and Goto-Kakizaki (GK) rats fed a high-fat diet (45% fat content) for 12 weeks, measuring insulin secretion and insulin release. RESULTS: Insulin secretion during oral glucose tolerance test (OGTT) was enhanced in high-fat diet-fed Wistar rats (WF) with normal glucose tolerance. Insulin secretion in high-fat diet-fed GK rats (GF) during OGTT also was enhanced together with deteriorated glucose tolerance. Basal insulin release from the isolated perfused pancreas at 3.3 m glucose in WF was comparable to that in normal chow-fed Wistar rats (WN), but basal insulin release in GF was remarkably higher than in normal chow-fed GK rats (GN). Stimulated insulin release induced by 16.7 m glucose was remarkably increased in WF compared with WN. Total insulin release at 16.7 m glucose in both GK rat groups was similar and minimal. CONCLUSION: These results indicate that normal pancreatic beta-cells have the ability to secrete sufficient insulin to compensate for the insulin resistance induced by a high-fat diet. In contrast, glucose metabolism in diabetic rats after high-fat diet deteriorated partly because of insufficient insulin secretion caused by genetic defects and lipotoxicity due to chronically high FFA levels.

Animals↗
PubMed2002

Prior exposure to high glucose augments depolarization-induced insulin release by mitigating the decline of ATP level in rat islets.

A brief exposure to elevated glucose augments the insulin secretory response of islets to subsequent stimulation. The site of this priming effect of glucose in the mechanism of the regulation of insulin secretion is not completely known, however. Insulin release triggered by a depolarizing concentration of K+ in the presence of basal glucose is markedly enhanced in primed rat islets. To clarify the role of priming on Ca(2+) and ATP efficacy in the exocytotic apparatus, islets were electrically permeabilized to vary the intracellular Ca(2+) and ATP concentrations according to the extracellular medium, and insulin release was evaluated. Ca(2+) and ATP efficacy in Ca(2+)- and ATP-dependent insulin secretion was not affected by priming, and alteration of the intracellular Ca(2+) concentration after depolarization cannot account for the phenomenon. There was no difference in ATP content before depolarization between nonprimed and primed islets. Moreover, the decline in ATP level after depolarization with basal glucose was observed in both primed and nonprimed islets. However, a reduced decline in ATP level in the early phase was observed in primed islets. In addition, oligomycin, a mitochondrial metabolism inhibitor, abolished the difference in ATP level between primed and nonprimed islets, suggesting that mitochondrial ATP production may be linked to the phenomenon.

Adenosine Triphosphate↗
PubMed2002

Effect of low-dose amiodarone on atrial fibrillation or flutter in Japanese patients with heart failure.

The efficacy and safety of amiodarone in the management of atrial fibrillation (AF) or flutter in 108 Japanese patients with heart failure was retrospectively examined. Thirty-four (41%) of the 82 patients who were in sinus rhythm after 1 month of amiodarone administration had their first recurrence, 70% of cases occurring within 1 year of initiation. The cumulative rates of maintenance of sinus rhythm were 0.68, 0.55, and 0.47 at 1, 3, and 5 years, respectively. Amiodarone was more effective in maintaining sinus rhythm in patients with paroxysmal AF or flutter than in those with the persistent form (p<0.05). The cumulative rates for cases that remained in permanent AF were 0.04, 0.11, and 0.14 at 1, 3, and 5 years, respectively. Apart from suppressing AF, the mean heart rate during Holter monitoring was significantly decreased with amiodarone therapy in cases of permanent AF. Adverse effects requiring the discontinuation of amiodarone therapy occurred in 16% of patients. Low-dose amiodarone therapy may prevent AF or flutter in Japanese patients with heart failure.

Amiodarone↗
PubMed2002

Hepatocyte nuclear factor-1alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter.

Mutations in the hepatocyte nuclear factor (HNF)-1alpha gene have been linked to subtype 3 of maturity-onset diabetes of the young (MODY), a disease characterized by a primary defect in insulin secretion. Here we show that the human GLUT2 gene is closely regulated by HNF-1alpha via sequences downstream of the transcriptional start site by interaction with transcriptional co-activator p300. The promoter region of the human GLUT2 gene was subcloned into luciferase expression plasmids that were transfected together with HNF-1alpha expression plasmid into a pancreatic beta-cell line, HIT-T15, to evaluate transcriptional activities. HNF-1alpha enhanced human GLUT2 promoter activity sixfold. Site-direct mutagenesis and footprint analyses showed that the HNF-1alpha binding site (+200 to +218) is critical in human GLUT2 gene expression. Furthermore, mammalian two-hybrid and immunoprecipitation studies revealed the transactivation domain of HNF-1alpha (amino acids 391-540) to interact with both the NH(2)-terminal region (amino acids 180-662) and the COOH-terminal region (amino acids 1,818-2,079) of p300. These findings demonstrated that HNF-1alpha binds to the 5'-untranslated region of GLUT2 and that p300 acts as a transcriptional co-activator for HNF-1alpha. In addition, these results provided new insight into the regulatory function of HNF-1alpha by suggesting a molecular basis for human GLUT2 gene expression.

5' Untranslated Regions↗
PubMed2002

Ouabain suppresses glucose-induced mitochondrial ATP production and insulin release by generating reactive oxygen species in pancreatic islets.

We examined the effects of reduced Na(+)/K(+)-ATPase activity on mitochondrial ATP production and insulin release from rat islets. Ouabain, an inhibitor of Na(+)/K(+)-ATPase, augmented 16.7 mmol/l glucose-induced insulin release in the early period but suppressed it after a delay of 20-30 min. Unexpectedly, the ATP content in an islet decreases in the presence of 16.7 mmol/l glucose when Na(+)/K(+)-ATPase activity is diminished by ouabain, despite the reduced consumption of ATP by the enzyme. Ouabain also suppressed the increment of ATP content produced by glucose even in Ca(2+)-depleted or Na(+)-depleted conditions. That mitochondrial membrane hyperpolarization and O(2) consumption in islets exposed to 16.7 mmol/l glucose were suppressed by ouabain indicates that the glycoside inhibits mitochondrial respiration but does not produce uncoupling. Ouabain induced mitochondrial reactive oxygen species (ROS) production that was blocked by myxothiazol, an inhibitor of site III of the mitochondrial respiratory chain. An antioxidant, alpha-tocopherol, also blocked ouabain-induced ROS production as well as the suppressive effect of ouabain on ATP production and insulin release. However, ouabain did not directly affect the mitochondrial ATP production originating from succinate and ADP. These results indicate that ouabain suppresses mitochondrial ATP production by generating ROS via transduction, independently of the intracellular cationic alternation that may account in part for the suppressive effect on insulin secretion.

Adenosine Triphosphate↗
PubMedDate not supplied

Insulin independence after living-donor distal pancreatectomy and islet allotransplantation.

Rising demand for islet transplantation will lead to severe donor shortage in the near future, especially in countries where cadaveric organ donation is scarce. We undertook a successful transplantation of living-donor islets for unstable diabetes. The recipient was a 27-year-old woman who had had brittle, insulin-dependent diabetes mellitus for 12 years. The donor, who was a healthy 56-year-old woman and mother of the recipient, underwent a distal pancreatectomy. After isolation, 408 114 islet equivalents were transplanted immediately. The transplants functioned immediately and the recipient became insulin-independent 22 days after the operation. The donor had no complications and both women showed healthy glucose tolerance. Transplantation of living-donor islets from the distal pancreas can be sufficient to reverse brittle diabetes.

Adult↗