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1.
Mol Cell Endocrinol ; 527: 111240, 2021 05 01.
Article in English | MEDLINE | ID: mdl-33676985

ABSTRACT

Chronic hyperglycemia causes pancreatic ß-cell dysfunction, impaired insulin secretion and the suppression of insulin gene expression. This phenomenon is referred to as glucotoxicity, and is a critical component of the pathogenesis of type 2 diabetes. We previously reported that the expression of candidate plasticity gene 16 (CPG16) was higher in rat pancreatic INS-1 ß-cells under glucotoxic conditions and CPG16 suppressed insulin promoter activity. However, the molecular mechanisms of the CPG16-mediated suppression of insulin gene expression are unclear. In this study, we found that CPG16 directly bound and phosphorylated jun dimerization protein 2 (JDP2), an AP-1 family transcription factor. CPG16 co-localized with JDP2 in the nucleus of INS-1 cells. JDP2 bound to the G1 element of the insulin promoter and up-regulated promoter activity. Finally, CPG16 suppressed the up-regulation of insulin promoter activity by JDP2 in a kinase activity-dependent manner. These results suggest that CPG16 suppresses insulin promoter activity by phosphorylating JDP2.


Subject(s)
Gene Expression Regulation , Insulin-Secreting Cells/metabolism , Insulin/biosynthesis , Protein Serine-Threonine Kinases/metabolism , Repressor Proteins/metabolism , Response Elements , Animals , Cell Line , Doublecortin-Like Kinases , Female , Insulin/genetics , Male , Mice , Mice, Inbred BALB C , Phosphorylation , Protein Serine-Threonine Kinases/genetics , Rats, Wistar , Repressor Proteins/genetics
2.
J Am Chem Soc ; 139(23): 7713-7716, 2017 06 14.
Article in English | MEDLINE | ID: mdl-28570064

ABSTRACT

A unique tandem reaction of sequence-controlled cationic copolymerization and site-specific hetero-Diels-Alder (DA) reaction is demonstrated. In the controlled cationic copolymerization of furfural and 2-acetoxyethyl vinyl ether (AcOVE), only the furan ring adjacent to the propagating carbocation underwent the hetero-DA reaction with the aldehyde moiety of another furfural molecule. A further and equally important feature of the copolymerization is that the obtained copolymers had unprecedented 2:(1 + 1)-type alternating structures of repeating sequences of two VE and one furfural units in the main chain and one furfural unit in the side chain. The specific DA reaction is attributed to the delocalization of the positive charge to the side furan ring.

3.
ACS Macro Lett ; 3(1): 80-85, 2014 Jan 21.
Article in English | MEDLINE | ID: mdl-35651114

ABSTRACT

Specifically designed alternating cationic copolymerization produced well-defined thermo- or pH-responsive polymers with complete acid-degradability. For example, a thermosensitive alternating copolymer with acid-labile acetal linkages in the main chain was obtained from the controlled cationic copolymerization of p-methoxybenzaldehyde (pMeOBzA) and a vinyl ether (VE) with an oxyethylenic side chain. The resulting copolymer exhibited a sharp thermosensitive phase transition in water. The same strategy but using different VEs with esters and benzaldehyde (BzA) yielded pH-responsive copolymers with nearly alternating sequences and narrow molecular weight distributions (MWDs). The alternately arranged acetal bonds in the copolymers allowed complete facile and rapid degradation under acidic conditions, which selectively produced low-molecular-weight compounds (MW ∼ 1-2 × 102).

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