RESUMO
This research is to explore the effects of traditional Chinese medicine Ginseng-spikenard heart-nourishing capsule on the inactivation of c-type Kv1.4 channels (Kv1.4∆N) in Xenopus laevis oocytes with two-electrode voltageclamp technique. Defolliculated oocytes (stage V-VI) were injected with transcribed cRNAs of ferret Kv1.4δN channels. During recording, oocytes were continuously perfused with ND96 solution (control group) and solution prepared from Ginseng-spikenard heart-nourishing capsule (experimental group). Results found that, at the command potential of +50 mV, the current of experimental group was reduced to 48.33±4.0% of that in control group. The inactivation time constants in control and experimental groups were 2962.56±175.35 ms and 304.13±36.22ms, respectively (P<0.05, n=7). The recovery time of fKv1.4∆N channel after inactivation in control group and experimental groups was 987±68.39 ms and 1734.15±98.45 ms, respectively (P<0.05, n=5). Ginseng-spikenard heart-nourishing capsule can inhibit the Kv1.4δN channel, which may be one of the mechanisms of underlying antiarrhythmia.
Assuntos
Antiarrítmicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Canal de Potássio Kv1.4/antagonistas & inibidores , Bloqueadores dos Canais de Potássio/farmacologia , Animais , Feminino , Furões , Técnicas de Transferência de Genes , Cinética , Canal de Potássio Kv1.4/genética , Canal de Potássio Kv1.4/metabolismo , Potenciais da Membrana , Oócitos , Xenopus laevisRESUMO
Adipokines such as leptin play important roles in the regulation of energy metabolism, particularly in the control of appetite. Here, we describe a hormone, mimecan, which is abundantly expressed in adipose tissue. Mimecan was observed to inhibit food intake and reduce body weight in mice. Intraperitoneal injection of a mimecan-maltose binding protein (-MBP) complex inhibited food intake in C57BL/6J mice, which was attenuated by pretreatment with polyclonal antibody against mimecan. Notably, mimecan-MBP also induced anorexia in A(y)/a and db/db mice. Furthermore, the expression of interleukin (IL)-1ß and IL-6 was up-regulated in the hypothalamus by mimecan-MBP, as well as in N9 microglia cells by recombinant mouse mimecan. Taken together, the results suggest that mimecan is a satiety hormone in adipose tissue, and that mimecan inhibits food intake independently of leptin signaling by inducing IL-1ß and IL-6 expression in the hypothalamus.
Assuntos
Tecido Adiposo/metabolismo , Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Leptina/metabolismo , Transdução de Sinais , Animais , Peso Corporal , Ingestão de Alimentos , Humanos , Hipotálamo/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Leptina/genética , Camundongos , Camundongos Knockout , Microglia/metabolismo , RatosRESUMO
AIM: To observe the effect of berberine on insulin secretion in rat pancreatic islets and to explore its possible molecular mechanism. METHODS: Primary rat islets were isolated from male Sprague-Dawley rats by collagenase digestion and treated with different concentrations (1, 3, 10 and 30 micromol/L) of berberine or 1 micromol/L Glibenclamide (GB) for 24 h. Glucose-stimulated insulin secretion (GSIS) assay was conducted and insulin was determined by radioimmunoassay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate cytotoxicity. The mRNA level of hepatic nuclear factor 4 alpha (HNF4alpha) was determined by reverse transcription polymerase chain reaction (RT-PCR). Indirect immunofluorescence staining and Western blot analysis were employed to detect protein expression of HNF4alpha in the islets. Glucokinase (GK) activity was measured by spectrophotometric method. RESULTS: Berberine enhanced GSIS rather than basal insulin secretion dose-dependently in rat islets and showed no significant cytotoxicity on islet cells at the concentration of 10 mumol/L. Both mRNA and protein expressions of HNF4alpha were up-regulated by berberine in a dose-dependent manner, and GK activity was also increased accordingly. However, GB demonstrated no regulatory effects on HNF4alpha expression or GK activity. CONCLUSION: Berberine can enhance GSIS in rat islets, and probably exerts the insulinotropic effect via a pathway involving HNF4alpha and GK, which is distinct from sulphonylureas (SUs).