RESUMO
In the Kondo insulator samarium hexaboride (SmB6), strong correlation and band hybridization lead to an insulating gap and a diverging resistance at low temperature. The resistance divergence ends at about 3 kelvin, a behavior that may arise from surface conductance. We used torque magnetometry to resolve the Fermi surface topology in this material. The observed oscillation patterns reveal two Fermi surfaces on the (100) surface plane and one Fermi surface on the (101) surface plane. The measured Fermi surface cross sections scale as the inverse cosine function of the magnetic field tilt angles, which demonstrates the two-dimensional nature of the conducting electronic states of SmB6.
RESUMO
The glucose transporter GLUT4 is well known to facilitate the transport of blood glucose into insulin-sensitive muscle and adipose tissue. In this study, molecular, immunohistochemical, and Western blot investigations revealed evidence that GLUT4 is also located in the mouse, rat, and human endocrine pancreas. In addition, high glucose decreased and insulin elevated the GLUT4 expression in pancreatic α-cells. In contrast, high glucose increased GLUT4 expression, whereas insulin led to a reduced expression level of the glucose transporter in pancreatic ß-cells. In vivo experiments showed that in pancreatic tissue of type 2 diabetic rats as well as type 2 diabetic patients, the GLUT4 expression is significantly increased compared to the nondiabetic control group. Furthermore, type 1 diabetic rats exhibited reduced GLUT4 transcript levels in pancreatic tissue, whereas insulin treatment of type 1 diabetic animals enhanced the GLUT4 expression back to control levels. These data provide evidence for the existence of GLUT4 in the endocrine pancreas and indicate a physiological relevance of this glucose transporter as well as characteristic changes in diabetic disease.
Assuntos
Transportador de Glucose Tipo 4/metabolismo , Ilhotas Pancreáticas/patologia , Ilhotas Pancreáticas/fisiopatologia , Adulto , Idoso , Animais , Especificidade de Anticorpos/imunologia , Linhagem Celular , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Transportador de Glucose Tipo 2/genética , Transportador de Glucose Tipo 2/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/imunologia , Humanos , Insulina/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Masculino , Camundongos , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos WistarRESUMO
The objective of the present study was to examine the effects of melatonin on transcripts of isoforms of calcium/calmodulin-dependent protein kinases in rat insulinoma beta-cells INS-1. Investigations show that calcium/calmodulin-dependent kinase IV and calcium/calmodulin-dependent kinase 2d are expressed in human and rat pancreatic islets and INS-1 cells. By application of either forskolin or 3-isobutyl-1-methylxanthine for 6 hours, calcium spiking was evoked and the release of insulin was increased. The expression of the calcium/calmodulin-dependent kinase IV and calcium/calmodulin-dependent kinase 2d transcripts was significantly increased due to forskolin or 3-isobutyl-1-methylxanthine. Acute melatonin treatment (6 h) in the presence of either forskolin or 3-isobutyl-1-methylxanthine caused a significant decrease in insulin release and induced significant downregulation of calcium/calmodulin-dependent kinase IV and calcium/calmodulin-dependent kinase 2d transcripts in INS-1 batch cultures. The attenuating effect of melatonin on transcripts could be almost completely reversed by preincubation with the melatonin receptor antagonist luzindole. Thus, the insulin-inhibiting effect of melatonin in INS-1 cells is associated with significant changes in transcripts of calcium-signaling components suggesting that melatonin influences gene expression of components, which are known to be involved in insulin secretion or insulin gene expression.
Assuntos
1-Metil-3-Isobutilxantina/farmacologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Colforsina/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Insulinoma/enzimologia , Melatonina/farmacologia , Animais , Cálcio/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Linhagem Celular Tumoral , Humanos , Secreção de Insulina , Células Secretoras de Insulina/enzimologia , Células Secretoras de Insulina/metabolismo , Insulinoma/tratamento farmacológico , Insulinoma/genética , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Ratos , Ratos WistarRESUMO
Evidence has previously been presented that circadian rhythms play a role in islet hormone secretion. Here, RT-PCR was used to monitor the circadian expression of ether-a-go-go-related gene (Erg) potassium channel isoforms and Erg1 splice variants. Immunohistochemistry was used to identify the pancreatic distribution patterns of ERG1a and ERG1b, as well as ERG2 and ERG3. The influence of ERG on insulin secretion was monitored by perfusion of rat INS-1 beta-cells with the blockers E-4031 and rBeKm-1. We identified Erg1a, Erg1b, Erg2 and Erg3 transcripts in islets and INS-1 cells. Immunohistochemistry showed differential expression of ERG isoforms in the islet. Ca(2+) imaging and electrophysiological recordings of INS-1 cells during ERG blocking by E-4031 indicated functional ERG channels. Serum shock treatment of INS-1 cells elicited a time-dependent expression response for Erg transcripts. These results add to the current understanding of the function of ERG channels in beta-cells and the circadian secretion processes of insulin.
Assuntos
Ritmo Circadiano/fisiologia , Canais de Potássio Éter-A-Go-Go/genética , Regulação da Expressão Gênica , Células Secretoras de Insulina/metabolismo , Animais , Cálcio/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Eletrofisiologia , Canais de Potássio Éter-A-Go-Go/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Imuno-Histoquímica , Células Secretoras de Insulina/efeitos dos fármacos , Masculino , Especificidade de Órgãos/efeitos dos fármacos , Perfusão , Piperidinas/farmacologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Transporte Proteico/efeitos dos fármacos , Piridinas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The central circadian oscillator of the suprachiasmatic nucleus controls diurnal rhythmicity of the body with light as its dominant zeitgeber. Recently, peripheral oscillators have been detected in liver and heart, which follow as yet unidentified cues. In this study real-time reverse transcription-polymerase chain reaction (RT-PCR) was used in analysis of the expression of the major clock genes Per1, Per2, Bmal1, Cry1, Tim (timeless) and Clock, as well as of the output genes Dbp and Rev-erbalpha in the pancreatic tissue of rats. The results presented here indicate a robust circadian expression of clock genes (e.g. Per1 and Bmal1) and the probable existence of a peripheral oscillator in the pancreas. Whether this oscillator regulates the diverse functions of the islets of Langerhans remains to be elucidated.
