Akiyo Yamauchi

Cyclin D1 activation through ATF-2 in Reg-induced pancreatic β-cell regeneration

Regenerating gene product (Reg) is induced in pancreatic β‐cells and acts as an autocrine/paracrine growth factor for regeneration via a cell surface Reg receptor. However, the manner by which Reg induces β‐cell regeneration was unknown. In the present study, we found that Reg increased phospho‐ATF‐2, which binds to −57 to −52 of the cyclin D1 gene to activate the promoter. The Reg/ATF‐2‐induced cyclin D1 promoter activation was attenuated by PI(3)K inhibitors such as LY294002 and wortmannin. In Reg knockout mouse islets, the levels of phospho‐ATF‐2, cyclin D1, and phospho‐Rb were greatly decreased. These results indicate that the Reg–Reg receptor system stimulates the PI(3)K/ATF‐2/cyclin D1 signaling pathway to induce β‐cell regeneration.

Microenvironments of 8-anilino-1-naphthalenesulfonate at the heptane-water interface: time-resolved total internal reflection fluorescence spectroscopy

Abstract Picosecond time-resolved total internal reflection fluorescence spectroscopy was applied to study the microenvironments of 8-anilino-1-naphthalenesulfonate molecules at the heptane-water interface. By analyzing the fluorescence decay profiles, it was found that the fluorophores in the vicinity of the interface are present in two different solvated structures. One of them is located up to a few nanometers from the interface, and the other is located in a relatively wide range toward the aqueous phase. The former solvated structure is the cause of a long fluorescence lifetime which reflects the low polarity or the extremely high viscosity of the microenvironments.

Autoantibodies to REG, a beta-cell regeneration factor, in diabetic patients

Background  Regenerating gene (Reg) product, Reg, acts as an autocrine/paracrine growth factor for beta‐cell regeneration. The presence of autoimmunity against REG may affect the operative of the regenerative mechanisms in beta cells of Type 1 and Type 2 diabetes patients. We screened sera from Type 1 and Type 2 diabetes subjects for anti‐REG autoantibodies, searched for correlations in the general characteristics of the subjects with the presence of anti‐REG autoimmunity, and tested the attenuation of REG‐induced beta‐cell proliferation by the autoanitibodies.

Thiazolidinediones inhibit REG Iα gene transcription in gastrointestinal cancer cells

REG (Regenerating gene) Ialpha protein functions as a growth factor for gastrointestinal cancer cells, and its mRNA expression is strongly associated with a poor prognosis in gastrointestinal cancer patients. We here demonstrated that PPARgamma-agonist thiazolidinediones (TZDs) inhibited cell proliferation and REG Ialpha protein/mRNA expression in gastrointestinal cancer cells. TZDs inhibited the REG Ialpha gene promoter activity, via its cis-acting element which lacked PPAR response element and could not bind to PPARgamma, in PPARgamma-expressing gastrointestinal cancer cells. The inhibition was reversed by co-treatment with a specific PPARgamma-antagonist GW9662. Although TZDs did not inhibit the REG Ialpha gene promoter activity in PPARgamma-non-expressing cells, PPARgamma overexpression in the cells recovered their inhibitory effect. Taken together, TZDs inhibit REG Ialpha gene transcription through a PPARgamma-dependent pathway. The TZD-induced REG Ialpha mRNA reduction was abolished by cycloheximide, indicating the necessity of novel protein(s) synthesis. TZDs may therefore be a candidate for novel anti-cancer drugs for patients with gastrointestinal cancer expressing both REG Ialpha and PPARgamma.

Saccharide recognition by Boronic Acid Fluorophore/Cyclodextrin Complexes in Water

Saccharides are important biological molecules because they are essential in such processes as nutrition and metabolism, and cell structure maintenance.1 Saccharides are also physiologically active and are involved in controlling an individual’s birth, differentiation and immunity. Because of these important properties, methods for in situ saccharide sensing in aqueous solution are very much required.1 In particular, continuous noninvasive monitoring of blood glucose is essential to the management of diabetes. Although biosensors using biological receptors (proteins) have been widely studied as tools for detecting saccharides in biological fluids, their poor stability limits their wide application in actual monitoring. Moreover, expected signals for biosensors are generally associated with changes in electrical current/potential, mass, and refractive index. These signals are not compatible with the imaging of intracellular events. To overcome the drawbacks of existing biosensors, an alternative method to detect saccharides must be developed without using biological receptors. For this purpose, two major strategies have been considered.1, 2 One is based on the use of multiple hydrogen bonding interactions mimicking the carbohydrate recognition by biological receptors.1–6 However, these synthetic receptors work only in organic solvents, since water interferes with the hydrogen-bonding interaction. Recently, Davis and coworkers have synthesized a water-soluble tricyclic poly amide receptor 1, which binds with saccharides in water, but whose affinity is low.7