Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4 alpha expression and glucokinase activity

Abstract

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 μmol/L) of berberine or 1 μmol/L Glibenclamide (GB) for 24 h. Glucose-stimulated insulin secretion (GSIS) assay was conducted and insulin was determined by radioimmunoassay. 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate cytotoxicity. The mRNA level of hepatic nuclear factor 4 alpha (HNF4α ) was determined by reverse transcription polymerase chain reaction (RT-PCR). Indirect immunofluorescence staining and Western blot analysis were employed to detect protein expression of HNF4α 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 μmol/L. Both mRNA and protein expressions of HNF4α were up-regulated by berberine in a dose-dependent manner, and GK activity was also increased accordingly. However, GB demonstrated no regulatory effects on HNF4α expression or GK activity. CONCLUSION: Berberine can enhance GSIS in rat islets, and probably exerts the insulinotropic effect via a pathway involving HNF4α and GK, which is distinct from sulphonylureas (SUs).

Berberine protects against high fat diet-induced dysfunction in muscle mitochondria by inducing SIRT1-dependent mitochondrial biogenesis

“…This is in agreement with several other studies that have demonstrated a role for BBR in the protection against HFD-induced insulin resistance and diabetes [25,30,46]. Notably, BBR not only acts in the insulin resistant tissues, but has also been shown to protect pancreatic beta cells function in high caloric and streptozotocin-induce diabetic models [51–53]. Several studies have shown that BBR needs to be administrated in high doses (380–560 mg/kg/day) in order to have a beneficial effect [25,27].…”

Protective effect of berberine on serum glucose levels in non-obese diabetic mice

“…In our previous studies, berberine showed potent antiinflammation potential [5], inhibited streptozotocin-induced apoptosis in mouse pancreatic islets through down-regulating Bax/Bcl-2 gene expression ratio in vitro [19], and protected pancreatic islets in NOD mice in vivo [15]. Dietary berberine at appropriate doses can be easily absorbed and reflected in sera in a dose-dependent manner [15], then enter pancreatic islet β-cells [20], and exert its anti-apoptotic effects possibly using its potent anti-inflammatory [5,21,22], and antioxidant activities [23], as well as down-regulating the Bax/Bcl-2 gene expression ratio [19]. In this study we assumed that berberine in vivo inhibited pancreatic islets apoptosis particularly through its potent anti-inflammation potential [5].…”

Antidiabetic Properties of Berberine: From Cellular Pharmacology to Clinical Effects

“…This has been demonstrated in diabetic rats, in which this effect is comparable with that of the sulfonylurea glibenclamide. 21 In the study by Wang et al, 21 berberine enhanced glucose-stimulated insulin secretion in a dose-dependent manner, increasing both mRNA expression of hepatic nuclear factor 4 α and glycokinase activity, thus providing an insulinotropic effect that was different from sulfonylureas. A dose-dependent insulin secretory effect has been described by other investigators, who also reported a favorable impact on plasma lipid levels.…”