Hiroshi Iwakura

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To investigate the precise role of Notch/Rbp-j signaling in the pancreas, we inactivated Rbp-j by crossing Rbp-j floxed mice with Pdx.cre or Rip.cre transgenic mice. The loss of Rbp-j at the initial stage of pancreatic development induced accelerated alpha and PP cell differentiation and a concomitant decrease in the number of Neurogenin3 (Ngn3)-positive(More)
Ghrelin, a 28-amino acid acylated peptide, displays strong GH-releasing activity in concert with GHRH. The fatty acid modification of ghrelin is essential for the actions, and des-acyl ghrelin, which lacks the modification, has been assumed to be devoid of biological effects. Some recent reports, however, indicate that des-acyl ghrelin has effects on cell(More)
Ghrelin is a recently identified endogenous ligand for the GH secretagogue receptor and is involved in a novel system for regulating GH release. However, little is known about its GH-releasing activity and other endocrine effects in humans. To address this issue, we studied the GH, ACTH, cortisol, PRL, LH, FSH, and TSH responses to synthetic human ghrelin.(More)
G protein-coupled receptor 40 (GPR40) is abundantly expressed in pancreatic beta cells in rodents, where it facilitates glucose-induced insulin secretion in response to mid- to long-chain fatty acids in vitro. However, GPR40 gene expression in humans has not been fully investigated, and little is known about the physiological and pathophysiological roles of(More)
Notch signaling regulates cell fate determination in various tissues. We have reported the generation of mice with a pancreas-specific knockout of Rbp-j using Pdx.cre mice. Those mice exhibited premature endocrine and ductal differentiation. We now generated mice in which the Rbp-j gene was inactivated in Ptf1a-expressing cells using Ptf1a.cre mice. The(More)
Ghrelin is an acylated peptide, whose lipid modification is essential for its biological activities. Previous studies demonstrated that it strongly stimulates GH release and has a potent orexigenic action. Meanwhile, there is enough evidence showing that feeding states influence plasma ghrelin levels. Fasting stimulates ghrelin secretion, and feeding(More)
Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In(More)
Uncoupling protein 3 (UCP3), which uncouples electron transport from ATP synthesis, is expressed at high levels in the skeletal muscle, an important organ in glucose and lipid metabolism. Because several reports proposed that fatty acids induced UCP3 gene expression in skeletal muscle in vivo, in the present study we examined the regulation of UCP3 gene(More)
We developed and analyzed two types of transgenic mice: rat insulin II promoter-ghrelin transgenic (RIP-G Tg) and rat glucagon promoter-ghrelin transgenic mice (RGP-G Tg). The pancreatic tissue ghrelin concentration measured by C-terminal radioimmunoassay (RIA) and plasma desacyl ghrelin concentration of RIP-G Tg were about 1000 and 3.4 times higher than(More)
A new method is proposed for designing IIR digital allpass filters with an equiripple phase response that can be proven to be optimal in the Chebyshev sense. The proposed procedure is based on the formulation of an eigenvalue problem by using the Remez exchange algorithm. Since there exists more than one eigenvalue in the general eigenvalue problem, we(More)