RESUMO
Type 2 Diabetes is closely associated with our daily diets and has become a global health problem with an increasing number of patients. Recent observational and randomized studies on vitamin D3 suggested that higher plasma 25-hydroxyvitamin D3 [25(OH)D3] concentrations and more vitamin D3 intake are associated with lower risk of type 2 diabetes, which is characterized by postprandial hyperglycemia due to inappropriate glucose stimulated insulin secretion (GSIS) and its age-dependent increase of onset. However, rapid action of dietary vitamin D3 on the postprandial glucose profile has not been analyzed. When vitamin D3 is orally ingested in mice aged 12-14 weeks during an oral glucose tolerance test (OGTT), the serum glucose profile was not changed. In contrast, when OGTT was performed with old mice aged 30-34 weeks, the glucose profile was dramatically improved with increased insulin secretion, suggesting that orally ingested vitamin D3 potentiated GSIS in aged mice. Interestingly, there was also a significant increase in plasma GLP-1 in these aged mice. Our results suggest that orally ingested dietary vitamin D3 in aged mice improves glucose metabolism as a GLP-1 enhancer.
Assuntos
Envelhecimento/metabolismo , Glicemia/metabolismo , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Células Enteroendócrinas/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Insulina/metabolismo , Administração Oral , Animais , Linhagem Celular , Células Enteroendócrinas/efeitos dos fármacos , Humanos , Hiperglicemia , Secreção de Insulina , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Resultado do TratamentoRESUMO
Smad2 is a critical mediator of TGF-ß signals that are known to play an important role in a wide range of biological processes in various cell types. Its role in the development of the CNS, however, is largely unknown. Mice lacking Smad2 in the CNS (Smad2-CNS-KO) were generated by a Cre-loxP approach. These mice exhibited behavioral abnormalities in motor coordination from an early postnatal stage and mortality at approximately 3 weeks of age, suggestive of severe cerebellar dysfunction. Gross observation of Smad2-CNS-KO cerebella demonstrated aberrant foliations in lobule IX and X. Further analyses revealed increased apoptotic cell death, delayed migration and maturation of granule cells, and retardation of dendritic arborization of Purkinje cells. These findings indicate that Smad2 plays a key role in cerebellar development and motor function control.
Assuntos
Apoptose , Comportamento Animal , Movimento Celular , Ataxia Cerebelar/metabolismo , Células de Purkinje/metabolismo , Proteína Smad2/metabolismo , Animais , Ataxia Cerebelar/genética , Ataxia Cerebelar/patologia , Humanos , Camundongos , Camundongos Knockout , Células de Purkinje/patologia , Proteína Smad2/genéticaRESUMO
Taste cells are chemosensory epithelial cells that sense distinct taste quality such as umami, sweet, bitter, sour and salty. Taste cells utilize G protein-coupled receptors to detect umami, sweet and bitter taste whereas ion channels are responsible for detecting salty and sour taste. Among these taste receptors, taste receptor type 2, T1R2 (or Tas1r2), has been identified as a sole sweet taste receptor in mammals that mediates sweet signals upon dimerization with T1R3. However, because of limited availability of reliable antibodies and low expression level of G protein-coupled receptors, it is uneasy to identify the cell-types that express these receptors in non-taste tissues. In this study, we have generated a T1R2-LacZ reporter knock-in mouse to investigate tissue distribution of T1R2 at a single-cell level. We found that the LacZ gene expression in these mice was faithful to the expression of T1R2 in the taste tissue and in the gastrointestinal tract where T1R3 expression has been reported. Surprisingly, T1R2 expression was also found in the testis. Mice homozygous for T1R2 deletion lacked T1R2 protein analyzed by the antibody raised against T1R2 peptide sequences. In summary, the T1R2 knock-in mouse is a powerful tool to analyze the putative targets for sweeteners as well as to study the physiological roles of T1R2 in detecting sugars.