Antibacterial activity and synergy of antibiotics with sanguisorbigenin isolated from Sanguisorba officinalis L. against methicillin-resistant Staphylococcus aureus.

The present study evaluated the antibacterial activity and the synergy of the sanguisorbigenin (SGB) from the dried root of Sanguisorba officinalis L. combined with ß-lactam antibiotics against methicillin-resistant Staphylococcus aureus. A total of six strains of reference strain and clinical isolates were used to determine the antibacterial activity using a broth microdilution assay, and the synergistic effects were determined using a checkerboard assay. To analyse the mechanism of synergy, we conducted the level of penicillin-binding protein 2a by western blot. In addition, quantitative RT-PCR was performed to analyse the mecA gene expression. The minimal inhibitory concentration values of SGB against six strains of S. aureus were in the range of 12·5-50 µg ml-1 , and there were synergy, or partial synergy effects when SGB was combined with antibiotics. Furthermore, when treated with SGB, the level of penicillin-binding protein 2a and the expression of the mecA gene was reduced significantly. In conclusion, this study demonstrated that SGB is a potential natural antibacterial agent against methicillin-resistant S. aureus that represents a considerable burden on the healthcare system worldwide, and may an exceptionally modulator of ß-lactam antibiotics.

Eleutheroside K isolated from Acanthopanax henryi (Oliv.) Harms suppresses methicillin resistance of Staphylococcus aureus.

Acanthopanax (A.) henryi (Oliv.) Harms contain many bioactive compounds commonly used in traditional Chinese medicine. The objective of the present study was to investigate the antibacterial activity of the single constituent, Eleutheroside K (ETSK) isolated from the leaves of A. henryi (Oliv.) Harms, against methicillin-resistant Staphylococcus (S.) aureus (MRSA). Broth microdilution assay was used to measure the minimal inhibitory concentration (MIC) and the MIC values of ETSK against eight clinical S. aureus strains were all 50 µg ml-1 . At sub-inhibitory concentrations, a synergistic effect between oxacillin (OXA) and ETSK was confirmed using checkerboard dilution assay and time-kill curve analysis. The bacteriostatic effect became more pronounced when ETSK was used in combination with detergent (Triton X-100) or ATPase inhibitor (N, N'-dicyclohexylcarbodiimide). According to western blot analysis, the down-regulated expression of Penicillin-binding protein 2a (PBP2a) further validated that the bacterial activity was inhibited when treated with ETSK in a dose-dependent manner. Results based on our study verified that ETSK significantly suppressed MRSA infections and emphasized the potential application of ETSK as a novel anti-MRSA natural drug.

Parkinson's disease and skin cancer risk: a nationwide population-based cohort study in Korea.

BACKGROUND: Previous studies have reported that patients with Parkinson's disease (PD) have a significantly lower risk of cancer. Studies reporting prevalence of skin cancers in Parkinson's disease mostly involve Caucasians. OBJECTIVE: A nationwide population-based study was conducted to determine the risk of skin cancer in patients diagnosed with PD in Korea. METHODS: Data obtained from National Health Insurance Claims records were used to retrieve information about 70 780 patients with newly diagnosed PD between January 2010 and December 2015. The control group included 353 900 sex- and age-matched patients without PD. In this nationwide population-based cohort study, we investigated the association between PD and skin cancer. RESULTS: The overall hazard ratio (HR) of skin cancers in patients with PD was 1.169 (95% CI, 1.005-1.359) compared with non-PD group. Among patients with PD, males aged above 65 had a 2.8-fold increase in the risk for melanoma development than the non-PD group (HR, 2.825; 95% CI, 1.395-5.721). In addition, female PD patients aged above 65 years showed a 1.3-fold increase in non-melanoma skin cancer risk than the non-PD group (HR, 1.305; 95% 1.073-1.589). CONCLUSION: Compared with the general population, Korean patients diagnosed with PD had a greater risk of skin cancer. Especially, male patients aged 65 years and above, and diagnosed with PD had a significant risk of melanoma development compared with control.

The impacts of the interaction of genetic variation, CYP11ß2 and NEDD4L, with sodium intake on pediatric obesity with gender difference: a 3-year panel study.

Backgrounds/Objectives:This panel study was to predict the incidences of pediatric obesity by the interaction of sodium (Na) intake and nine single-nucleotide polymorphisms (SNPs) of salt-sensitive genes (SSGs), ACE(angiotensin-converting enzyme), ADD1 G460W,AGT M235T,CYP11ß2 (cytochrome P450 family 11-subfamily ß-2, -aldosterone synthase),GNB3 C285T,GRK4(A142V)(G-protein-coupled receptor kinases type 4),GRK4 (A486V),NEDD4L (neural precursor cell expressed developmentally downregulated 4 like; rs2288774) and SLC12A3 (solute carrier family 12 (Na/Cl transporters)-member 3), selected from genome-wide association study. SUBJECTS/METHODS: Non-obese (non-OB) Korean children of 9 years old were recruited from eight elementary schools in Seoul in 2007 and 2009, each. Follow-up subjects (total=798) in 2010 and 2012 were final participants. Participants were classified as OB group for those whose body mass index were over the 85th percentile using the 'Korean National Growth Charts', and others were classified as non-OB. With nine SNPs typing, the genetic interaction with the variation of Na intake for 3 years was evaluated as an obesity risk. RESULTS: The obesity incidence rate for non-OB children at baseline after 3 years was 10.31%. Na intake in non-OB after 3 years was significantly decreased compared with the baseline, whereas Na intake reduction was undetectable in OB. We found gender differences on association between the changes of Na intake and the obesity incidence for 3 years by the SSG variation. Odds ratio for the obesity risk was 5.75 times higher in girls having hetero/mutant types of NEDD4L with higher Na intakes (Q2+Q3+Q4 in quartiles) compared with that in the wild type with the lowest Na intake (Q1). Girls with hetero/mutant of CYP11ß2 tended to increase the obesity incidence as Na intake increased (Q1

Prenatal diagnosis of congenital syphilis presenting with transient pleural effusion in the fetus: a case report and rising incidence of congenital syphilis in South Korea.

Congenital syphilis is preventable and curable if maternal infection is detected early, and pregnant women in Korea are screened routinely for this disease. Nevertheless, the incidence of congenital syphilis is not decreasing. Prenatal diagnosis of congenital syphilis is difficult and treatment is usually based on maternal syphilis serology. Prenatal ultrasonographic examination may sometimes reveal abnormal features suggesting congenital infection. The authors report a case of congenital syphilis that was diagnosed in both fetus and asymptomatic mother following detection on prenatal ultrasonography of transient fetal pleural effusion. The case is noteworthy for its sonographic presentation as fetal pleural effusion rapidly resolved spontaneously.

Mini-Mental Status Examination as predictors of mortality in the elderly.

OBJECTIVE: Because the number of elderly is increasing worldwide, cognitive dysfunction becomes important health care issue. This study investigated the association between cognitive dysfunction and mortality in the elderly. METHOD: Data were analyzed from a longitudinal mortality follow-up study of 2712 Korean elderly aged 60 and over, examined in 2002 with complete data followed an average 6.03 years. Measurements included socio-demographic and clinical factors and Mini-Mental State Examination (MMSE). MMSE was categorized into groups with no, mild, or moderate cognitive dysfunction, and the subscores of MMSE domains were categorized into no dysfunction or dysfunction. The Cox proportional hazards models were conducted to examine the association between MMSE score and mortality, after adjusting for age, gender, education and other socio-demographic factors. RESULTS: Death during follow-up occurred in 318 subjects. The mortality risk was significantly associated with the elderly with mild cognitive dysfunction [hazard ratio (HR) = 1.93] and with moderate cognitive dysfunction (HR = 2.66). 'Orientation-to-time' (HR = 1.39) and 'Attention' (HR = 1.48) domains of MMSE were independently associated with mortality. CONCLUSION: This study showed that cognitive dysfunction independently predicted mortality in the elderly. Cognitive dysfunction should be considered part of identifying the elderly at high risk for mortality.

Curcumin decreases oleic acid-induced lipid accumulation via AMPK phosphorylation in hepatocarcinoma cells.

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic syndromes and is characterized by the accumulation of hepatic triglycerides (TG), which result from an imbalance between uptake, synthesis, export, and oxidation of fatty acids. Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric, was found to prevent obesity and diabetes in mouse models. However, a hypolipidemic effect of curcumin in oleic acid- induced hepatocarcinoma cells has not been reported. In this study, we examined the effect of curcumin on reducing lipid accumulation in hepatic cells. MATERIALS AND METHODS: Hepatocytes were treated with oleic acid (OA) containing with or without curcumin to observe the lipid accumulation by Oil Red O stain. We also tested the effects of curcumin on triglycerides (TG) and total cholesterol (TC) in HepG2 cells. Western blot and reverse transcription polymerase chain reaction (RT-PCR) was used to measure sterol regulatory element binding proteins-1 (SREBP-1), fatty acid synthase (FAS), peroxisome proliferator-activated receptor (PPAR)-α, and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) expression. RESULTS: Curcumin suppressed OA-induced lipid accumulation and TG and TC levels. Also, curcumin decreased hepatic lipogenesis such as SREBP-1, and FAS. Besides, we also found out the antioxidative effect of curcumin by increasing the expression of PPARα. Curcumin increased AMPK phosphorylation in hepatocytes. CONCLUSIONS: These results indicated that curcumin has the same ability to activate AMPK and then reduce SREBP-1, and FAS expression, finally leading to inhibit hepatic lipogenesis and hepatic antioxidative ability. In this report, we found curcumin exerted a regulatory effect on lipid accumulation by decreasing lipogenesis in hepatocyte. Therefore, curcumin extract may be active in the prevention of fatty liver.

Anti-inflammatory effects of Hylomecon hylomeconoides in RAW 264.7 cells.

BACKGROUND AND OBJECTIVES: Papaveraceae serve as a rich source of various alkaloids which have anti-inflammatory effect. MATERIALS AND METHODS: In this study, we investigated the effect of Hylomecon hylomeconoides ethanol extract (HHE) on lipopolysaccharide (LPS)-induced NO and interleukin-6 (IL-6) production in RAW 264.7 cells. RESULTS: HHE inhibited LPS-induced NO and IL-6 production. Moreover, HHE suppressed the phosphorylation of ERK1/2 and p38 in LPS-induced RAW 264.7 in a dose-dependent manner. Furthermore, major constituents, dihydrosanguinarine and 6-methoxydihydrosanguinarine, of the chloroform-soluble extract were analyzed. CONCLUSIONS: Taken together, the results of this study indicate that the anti-inflammatory effects of HHE may occur via the inhibition of NO and IL-6 expression through the down-regulation of MAP kinase (ERK1/2, p38) phosphorylation in RAW 264.7 cells.

Antibacterial activity of bark of Alnus pendula against methicillin-resistant Staphylococcus aureus.

BACKGROUND AND OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) infections are a rapidly growing health problem around the globe. Recently, there has been considerable interest in the use of plant materials as an alternative method to control pathogenic microorganisms. In this study we evaluated the antibacterial activity of bark of Alnus pendula against MRSA. MATERIALS AND METHODS: The MIC determination was done using the microdilution broth method and bacterial growth was determined by measuring optical density using spectrophotometer. RESULTS: Alnus pendula bark EtOH extract and fractions (F-1, -2, -3 and -4) were investigated against MRSA. The most active fractions (F-3 and F-4) led to the isolation of oregonin (ORE) and hirsutanone (HIR). These compounds were active against MRSA strains with minimum inhibitory concentrations (MICs) ranging from 31.25 to 250 microg/ml MIC and 2 MIC of HIR completely inhibited the growth of MRSA. CONCLUSIONS: The bark EtOH extract of Alnus Pendula has potent antibacterial activity against MRSA.

Anti-inflammatory effect of sinomenine by inhibition of pro-inflammatory mediators in PMA plus A23187-stimulated HMC-1 Cells.

BACKGROUND AND OBJECTIVES: Sinomenine is an alkaloid compound and a prominent anti-inflammatory agent found in the root of the climbing plant Sinomenium acutum. However, its effects on the mechanism of human mast cell line (HMC)-1-mediated inflammation remained unknown. MATERIALS AND METHODS: To provide insight into the biological effects of sinomenine, we examined its influence on the pro-inflammatory cytokine production in HMC-1 cells stimulated by phorbol 12-myristate-13-acetate (PMA) plus A23187 by evaluating the stimulated cells in the presence or absence of sinomenine. In the present study, the pro-inflammatory cytokine production was measured using ELISA, Reverse Transcription-polymerase chain reaction (RT-PCR) and nuclear factor (NF)-kappaB, mitogen-activated protein kinases (MAPKs) pathway activation, as determined by Western blot analysis. Also, cyclooxygenase (COX)-2 expression was measured through Western blot and RT-PCR analysis. RESULTS: Sinomenine inhibited the pro-inflammatory cytokine production induced by PMA plus A23187 in a dose-dependent manner. Furthermore, sinomenine inhibited the phosphorylations of extracellular signal-regulated kinase (ERK) and p38 MAPKs as well as the translocation of NF-kappaB p65 through reduced IkappaBalpha degradation. In addition, sinomenine suppressed COX-2 protein and mRNA expression dose-dependently. CONCLUSIONS: Taken together, the results of this study indicate that the anti-inflammatory effects of sinomenine may occur via the inhibition of pro-inflammatory cytokine and COX-2 production through the inhibition of MAPKs and NF-kappaB pathway activation by PMA plus A23187 stimulation in HMC-1 cells.

Antimicrobial activity of the constituents of Smallanthus sonchifolius leaves against methicillin-resistant Staphylococcus aureus.

BACKGROUND AND OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) has been a serious problem as its infection is associated with higher mortality and increase cost worldwide. In the present study, the antibacterial activity of enhydrin, polymatin B, allo-schkuhriolide from the leaves of Smallanthus sonchifolius was investigated. MATERIAL AND METHODS: Enhydrin, polymatin B, allo-schkuhriolide from the leaves of Smallanthus sonchifolius were tested for antimicrobial activity using micro dilution broth method against 2 strains of ATCC 33591, ATCC 25923 and 15 strains of clinical isolates MRSA. RESULTS: The antibacterial activity of Smallanthus sonchifolius can safely be attributed to enhydrin as polymatin B, and allo-schkuhriolide are not showing any activity against Staphylococcus aureus strains. The enhydrin showed good antibacterial activity against all tested strains (MIC = 125-500 microg/ml). DISCUSSION: These results suggest that only enhydrin can be considered as an antibacterial drug against MRSA.

3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitory effect of Vitis vinifera.

Activity-guided fractionation of the methanol extract of Vitis vinifera bark led to the isolation of epsilon-viniferin, ampelopcin A, vitisin A and vitisin B. Vitisin A and vitisin B showed a remarkable inhibitory activity against 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase with IC50 value of 42.1 microM and 23.9 microM, respectively.

An extract of Polygonum multiflorum protects against free radical damage induced by ultraviolet B irradiation of the skin.

Over the last decades, the incidence of ultraviolet B (UVB)-related skin problems has been increasing. Damages induced by UVB radiation are related to mutations that occur as a result of direct DNA damage and/or the production of reactive oxygen species. We investigated the anti-oxidant effects of a Polygonum multiflorum thumb extract against skin damage induced by UVB irradiation. Female SKH-1 hairless mice were divided into three groups: control (N = 7), distilled water- (N = 10), and P. multiflorum extract-treated (PM, N = 10) groups. The PM (10 g) was extracted with 100 mL distilled water, cryo-dried and 9.8 g was obtained. The animals received a topical application of 500 microL distilled water or PM extract (1, 2, 4, 8, and 16%, w/v, dissolved in distilled water) for 30 min after UVB irradiation (wavelength 280-320 nm, 300 mJ/cm(2); 3 min) of the dorsal kin for 14 days, and skin immunohistochemistry and Cu,Zn-superoxide dismutase (SOD1) activity were determined. SOD1 immunoreactivity, its protein levels and activities in the skin were significantly reduced by 70% in the distilled water-treated group after UVB irradiation compared to control. However, in the PM extract-treated groups, SOD1 immunoreactivity and its protein and activity levels increased in a dose-dependent manner (1-16%, w/v, PM extract) compared to the distilled water-treated group. SOD1 protein levels and activities in the groups treated with 8 and 16%, w/v, PM extract recovered to 80-90% of the control group levels after UVB. These results suggest that PM extract strongly inhibits the destruction of SOD1 by UV radiation and probably contains anti-skin photoaging agents.

Settling characteristics of problem algae in the water treatment process.

The settling velocity or removal rates of problem algae in the water treatment process and their flocculants were measured with settling column (SETCOL) and fluorometric method. Our research who were centred on the algal density and shape affecting the settling. The settling velocities of large algae ranged from 0.1 cm/h to 2.6 cm/h, whereas those of small algae were below 1.0 cm/h. The settlings of algae in the stationary growth phase significantly increased and dead algae corresponded with the declining algae. The extent of deformation, which was expressed as the coefficient of form resistance of the algae had the great influences upon the settling. The most extreme deformed algae were needle-shaped ones like Synedra acus, which was known to be a problem in water treatment processes in Korea. Changes in the settling velocity of algae were correlated with algal volume and morphology rather than cell density.

Uteroglobin gene polymorphisms affect the progression of immunoglobulin A nephropathy by modulating the level of uteroglobin expression.

Uteroglobin (UG) is an anti-inflammatory/immunomodulatory protein. Targeted disruption of UG rendered mouse glomerulonephritis resembling immunoglobulin (Ig)A nephropathy (IgAN). Sequence analysis on exon 1 of UG showed several putative binding sites for transcription factors, and polymorphisms in this site might influence the expression level of UG as a competitive protein. We speculated that the single nucleotide polymorphism at the 38th nucleotide (A to G) from the transcription initiation site of UG exon 1 would impact the progression of IgA nephropathy (IgAN). Polymerase chain reaction-restriction fragment length polymorphism and single-strand conformation polymorphism were instituted to determine the genetic polymorphism. Luciferase assay was performed using the gene constructs containing a region 404-bp long located upstream of UG exon 1 initiation site to analyse whether this polymorphism would affect the expression level. UG polymorphism was distributed no differently in patients with IgAN (n = 111) compared to 60 healthy control subjects. An excess of A genotype was found in one patient having progressive disease (P = 0.03) and the risk for the disease progression increased as the number of A alleles increased (P for trend = 0.03) after follow-up for 116 months. The odds ratio for progression with the AA genotype was 4.9 (95% Cl = 1.0-23.9) compared to patients having the GG genotype. Significant interactive effects of hypertension and genetic polymorphisms of UG on the disease progression were observed (P for interaction = 0.001). In the luciferase assay, the gene construct with A at the 38th site showed a decreased activity of 74 +/- 8.4% compared to that showed by G gene construct. Our results suggest that polymorphism at the 5' UTR region of UG exon 1 is an important marker for the progression of IgAN and may modulate the level of protein expression.

Serum melanotransferrin, p97 as a biochemical marker of Alzheimer's disease.

The protein melanotransferrin (p97) is associated with the brain lesions of Alzheimer's disease (AD) and is a potential marker of the disorder. We measured serum p97 concentrations in 211 subjects: 71 patients with AD, 56 patients with non-AD-type dementia, and 84 normal control subjects. Serum p97 concentrations were elevated 3- to 4-fold in AD (median 15.00 pg/microl, interquartile range 10.20-17.00 pg/microl) as compared to non AD dementia (2.85 pg/microl, 1.93-7.15 pg/microl) and normal controls (3.20 pg/microl, 2.55-3.95 pg/microl). The mean elevation was significant at 13.54 +/- 3.72 pg/microl, even in the 38 subjects with mild AD (CDR stage 0.5-1). Receiver operating characteristic analyses confirmed an optimal diagnostic threshold of 10.0 pg/microl, which yielded over-all accuracy of 0.882 to 0.915. Serum p97 is a candidate marker of AD, even in the early stage when clinical diagnosis is most uncertain.

Rapid purification, partial characterization, and antimicrobial spectrum of the bacteriocin, Pediocin AcM, from Pediococcus acidilactici M.

The bacteriocin from Pediococcus acidilactici M, designated as Pediocin AcM, was rapidly purified to homogeneity by the pH mediated cell adsorption-desorption method and semi-preparative reversed-phase HPLC. The purification yield was 40.4% and the specific activity was increased by 2450-fold. It gave a single band and a single peak on SDS-PAGE and HPLC analysis, respectively. When subjected to electrospray LC-MS analysis, the protein was found to be highly pure and the molecular weight was determined as 4,618 Da. High concentration of the bacteriocin (> 50 micrograms/ml) showed good resistance to extremes of pH (1-12) and temperature (121 degrees C). Pediocin AcM was deduced to be a monomer with an intra-peptide disulfide bond from the results of reversed-phase analytical HPLC analyses after reduction, oxidation and trypsin digestion. P. acidilactici M inhibited a large number of bacteria, including Staphylococcus aureus, Listeria monocytogenes, Clostridium perfringens, Bacillus coagulans, B. cereus, and Aeromonas hydrophila.

Enantiomeric synthesis of (S)-2-methylbutanoic acid methyl ester, apple flavor, using lipases in organic solvent.

Enantiomeric selective synthesis of (S)-2-methylbutanoic acid methyl ester, which is known as a major apple and strawberry flavor, was performed from racemic 2-methylbutanoic acid using lipases in organic solvent. Among 20 lipases, lipase IM 20 (immobilized lipase of Rhizomucor miehei), lipase AP (Aspergillus niger), and lipase FAP-15 (Aspergillus javanicus) exhibited higher enzymatic activities and enantioselectivities and were selected for the synthesis of (S)-2-methylbutanoic acid methyl ester. Using these enzymes, the reaction conditions such as temperature and lyophilizing pH were optimized, and kinetic parameters were determined. All of the reactions were performed in isooctane, which was identified as the best reaction media for nonaqueous systems. At 20 degrees C maximum enantiomeric excess was observed, while synthetic activity increased as the temperature increased. Only lipases lyophilized at pH 5.5, 6. 0, 6.5, and 7.0 showed synthetic activity. In this pH range, enantioselectivities were not influenced by the lyophilizing pH. The K(M,S) and K(M,R) values for ester synthetic activity of lipase were 1120 and 1240 mM, respectively. Enzyme activity was inhibited by (S)-2-methylbutanoic amide, and its K(i) was calculated as 84 mM. (S)-2-Methylbutanoic amide acted as a competitive inhibitor.

Effects of organic solvents on lipase for fat splitting.

The effect of organic solvents on the stability and catalytic activity of the microbial lipase from Candida rugosa for hydrolysis of triglyceride (fat splitting) has been examined. The solvents examined were 5 hydrocarbons (n-hexane, n-heptane, n-octane, iso-octane and cyclohexane) and 3 ethers (diethyl-ether, diisopropylether and di-n-butylether). The results revealed that iso-octane and cyclohexane are superior to the other solvents examined for enzymatic fat splitting in organic solvent systems.

Long-term central infusion of adiponectin improves energy and glucose homeostasis by decreasing fat storage and suppressing hepatic gluconeogenesis without changing food intake.

Adiponectin is known to be an anti-diabetic adipocytokine. However, the action mechanism by which it produces this effect remains controversial. In the present study, we investigated the long-term central effect of adiponectin on energy homeostasis, peripheral insulin resistance, ß-cell function and mass in rats and aimed to determine the mechanism by which its effect was achieved. Intracerebroventricular infusion of adiponectin (50 ng/h) and artificial cerebrospinal fluid (CSF) was conducted by means of an osmotic pump for 4 weeks on nondiabetic rats and 90% pancreatectomised diabetic rats that were both fed 45% energy fat diets. After 4-weeks of treatment, i.c.v. adiponectin improved hypothalamic insulin/leptin signalling in nondiabetic and diabetic rats compared to i.c.v. CSF but it did not change the phosphorylation of AMP kinase (AMPK) in the hypothalamus. Adiponectin infusion decreased epididymal fats, representing visceral fat, by increasing energy expenditure and fat oxidation. During the euglycaemic hyperinsulinaemic clamp, i.c.v. adiponectin improved whole body insulin sensitivity and decreased hepatic glucose output in the hyperinsulinaemic state by attenuating hepatic insulin resistance. Central infusion of adiponectin did not modulate glucose-stimulated insulin secretion during the hyperglycaemic clamp compared to i.c.v. CSF infusion but it enhanced insulin sensitivity at a hyperglycaemic state. Although there were no changes in insulin secretion capacity, central adiponectin increased pancreatic ß-cell mass in nondiabetic and diabetic rats as a result of decreasing ß-cell death. In conclusion, long-term central infusion of adiponectin enhanced energy homeostasis by increasing energy expenditure via activating hypothalamic leptin and insulin signalling pathways but without potentiating AMPK signalling; it also improved glucose homeostasis by attenuating insulin resistance.