Chromosome-level genome assembly and functional characterization of terpene synthases provide insights into the volatile terpenoid biosynthesis of Wurfbainia villosa.

Wurfbainia villosa is a well-known medicinal and edible plant that is widely cultivated in the Lingnan region of China. Its dried fruits (called Fructus Amomi) are broadly used in traditional Chinese medicine for curing gastrointestinal diseases and are rich in volatile terpenoids. Here, we report a high-quality chromosome-level genome assembly of W. villosa with a total size of approximately 2.80 Gb, 42 588 protein-coding genes, and a very high percentage of repetitive sequences (87.23%). Genome analysis showed that W. villosa likely experienced a recent whole-genome duplication event prior to the W. villosa-Zingiber officinale divergence (approximately 11 million years ago), and a recent burst of long terminal repeat insertions afterward. The W. villosa genome enabled the identification of 17 genes involved in the terpenoid skeleton biosynthesis pathway and 66 terpene synthase (TPS) genes. We found that tandem duplication events have an important contribution to the expansion of WvTPSs, which likely drove the production of volatile terpenoids. In addition, functional characterization of 18 WvTPSs, focusing on the TPS-a and TPS-b subfamilies, showed that most of these WvTPSs are multi-product TPS and are predominantly expressed in seeds. The present study provides insights into the genome evolution and the molecular basis of the volatile terpenoids diversity in W. villosa. The genome sequence also represents valuable resources for the functional gene research and molecular breeding of W. villosa.

Obesity-associated secondary hypogonadism in young and middle-aged men in Guangzhou: A single-centre cross-sectional study.

AIM: Male obesity-associated secondary hypogonadism (MOSH) is becoming a public health issue. We aimed to know MOSH among young and middle-aged men in our hospital, to analyse their sex hormones and other index, and to determine leptin as a risk factor for MOSH. METHODS: In total, 258 men (ages ranging from 20 to 60, mean 38 ± 15) were enrolled in this study, and 242 of these men had their complete data, body mass index (BMI), waist circumference and sex hormones retrospectively investigated. The leptin and lipid levels were also evaluated, and comparisons were made between young (20-39 years old) and middle-aged (40-60 years old) men. RESULTS: Among all the participants, 7 were thin, with a BMI < 18.5 kg/m2 , 95 had a normal BMI (18.5 ≤ BMI < 23.9 kg/m2 ), 87 (35.9%) were overweight (24 ≤ BMI ≤ 27.9 kg/m2 ) and 53 (21.9%) were obese (BMI ≥ 28 kg/m2 ), 173 (71.5%) had a waist sized ≥ 85 cm. Among the 242 men, 104 (43%) had hypogonadism (TT ≤ 331.412 ng/dL). Compared with the men of normal weight, the level of testosterone of the obese men decreased (P = .006), while the level of serum lipids (including total cholesterol, TG and low-density lipoprotein cholesterol, P < .05) was elevated, higher UA, FSH and leptin were also present in the obese men. There were 83 (34.2%) men with MOSH. Compared with middle-aged men with MOSH, the FSH in young men was significantly reduced (P < .05); no significant increase in estradiol was observed in the MOSH group. The leptin levels in the MOSH group were significantly higher than those in the hypogonadism only group (P < .001). CONCLUSION: Obesity increases the prevalence of hypogonadism. The decrease in testosterone levels in young men maybe due to inhibition of the hypothalamic pituitary gonadal axis. Leptin is an independent risk factor for MOSH.

Theoretical study on the regioselective photoisomerization of asymmetric N,C-chelate organoboron compounds.

Herein, the complete active space self-consistent field (CASSCF) and its second-order perturbation (CASPT2) methods combined with time-dependent density functional theory (TD-DFT) calculations were employed to investigate the isomerization reaction mechanisms of an asymmetric N,C-chelate organoboron compound, B(ppy)MesPh, in the ground (S0) state and the first singlet excited (S1) state. Our calculations show that isomerizations proceed via different pathways in the S0 and S1 states,; however, the energy barriers for mesityl isomerization are higher than those for phenyl isomerization in both states; this is in good agreement with the experimentally observed regioselectivity (S. Wang, et al. Angew. Chem., Int. Ed., 2017, 56, 6093-6097). Photoisomerization is motivated by charge transfer from two phenyl rings to the pyridyl moiety and initiated by the cleavage of the B-Cppy bond, followed by the formation of a boracyclopropane ring via an (S1/S0)X conical intersection and a biradical intermediate. Both steric and electronic features were found to be important for regioselective photoisomerization. Our results not only shed light on the experimental observations, but also provide valuable details on the excited state dynamics of organoboron compounds and can facilitate further syntheses and applications.

[Diagnostic criteria for late-onset hypogonadism: A preliminary study].

OBJECTIVE: To determine the stability of androgen indexes by analyzing the relationship of androgen indexes with the results of late-onset hypogonadism (LOH) questionnaire investigations, and offer some reference for the application of the diagnostic criteria for LOH released by The Chinese Society of Andrology in 2009. METHODS: This study included 1 003 males aged 40 years or older who had accomplished the questionnaires of Androgen Deficiency in Aging Males (ADAM), Aging Males' Symptoms Scale (AMS), and International Index of Erectile Function-5 (IIEF-5). We evaluated the correlation of androgen indexes with the results of the questionnaire investigation, repeated the examination of androgen indexes for the subjects with total testosterone (TT) ≤11.5 nmol/L after an average of 1.5 years, and analyzed the factors inducing changes of androgen indexes. RESULTS: Free testosterone index (FTI) ≤ 0.42 (OR, 1.369) and calculated free testosterone (cFT) ≤ 0.3 nmol/L (OR, 1.302) were considered as the risk factors of LOH in AMS, and so were testosterone secretion index (TSI) ≤ 2.8 nmol/IU (OR, 1.679) and cFT ≤ 0.3 nmol/L (OR, 1.371) in IIEF-5. Paired t-test on the results of the examination performed twice showed significant differences in the levels of TT, TSI, cFT, and FT (P<0.05). CONCLUSIONS: Decreased testosterone may cause the diversity of LOH symptoms and hence the fluctuation of androgens. Therefore, the diagnosis of LOH depends on androgen indexes, varied symptoms in the questionnaires, and relief of the symptoms after testosterone therapy.

[Association of serum testosterone with atherosclerosis in middle-aged and elderly men].

OBJECTIVE: To investigate the association between the level of serum testosterone and atherosclerosis in middle-aged and elderly men. METHODS: We conducted a population-based study of 413 males aged 40-75 years in a community in Guangzhou. We obtained the sociodemographic characteristics, clinical data, physical measurements, and laboratory results of sex hormones, blood glucose, and blood lipid of the subjects. We also measured the carotid intima media thickness (CIMT) by color Doppler ultrasonography. RESULTS: The subjects were divided into a carotid atherosclerosis (CAS) group (CIMT ≥ 0.9 mm) and a non-CAS group (CIMT < 0.9 mm). The medians of free testosterone (FT) were 57.41 and 59.72 pmol/L in the CAS and non-CAS groups, respectively (P = 0.005), and no significant difference was found between the two groups in total testosterone (TT). The levels of serum FT and TT were negatively correlated to CIMT, with Spearman's rank correlation coefficients of -0.126 (P = 0.011) and -0.188 (P < 0.001), respectively. The incidence rates of CAS were 23.30, 13.46, 17.48, and 7.77% in the Q1, Q2, Q3, and Q4 groups, respectively according to the quartile of FT (P for trend = 0.008) and 17.48, 18.27, 16.50, and 9.71% respectively according to the quartile of TT (P for trend = 0.116). Based on the quartile of FT and after adjustment for age, waist circumference, systolic blood pressure, and HbAlc, the risk of CAS was significantly increased in the Q1 group as compared with Q4 (OR = 2.491, 95% CI 1.01-6.149), but no statistically significant differences were observed according to the quartile of TT. CONCLUSION: A low serum FT level may be a risk factor of atherosclerosis in Chinese men aged 40 years or older.

Elastin-Derived VGVAPG Fragment Decorated Cell-Penetrating Peptide with Improved Gene Delivery Efficacy.

Cell-penetrating peptides (CPPs) are attractive non-viral gene delivery vectors due to their high transfection capacity and safety. Previously, we have shown that cell-penetrating peptide RALA can be a promising gene delivery vector for chronic wound regeneration application. In this study, we engineered a novel peptide called RALA-E by introducing elastin-derived VGVAPG fragment into RALA, in order to target the elastin-binding protein on the cell surface and thus improve delivery efficacy of RALA. The transfection efficiency of RALA-E was evaluated by transfecting the HEK-293T and HeLa cell lines cells with RALA-E/pDNA complexes and the flow-cytometry results showed that RALA-E significantly increased the transfection efficiency by nearly 20% in both cell lines compared to RALA. Inhibition of pDNA transfection on HEK-293T cells via chlorpromazine, genistein and mßCD showed that the inhibition extent in transfection efficiency was much less for RALA-E group compared to RALA group. In addition, RALA-E/miR-146a complexes showed up to 90% uptake efficiency in macrophages, and can escape from the endosome and enter the nucleus to inhibit the expression of inflammation genes. Therefore, the developed RALA-E peptide has high potential as a safe and efficient vector for gene therapy application.

Effects of Leonurine on L-type calcium channel in rat ventricular myocytes.

Leonurine (Leo) is a special alkaloid principle of Herba leonuri that has recently been suggested to improve cardiovascular functions. To date, there is no direct ionic evidence of Leo on regulating calcium channels in the heart. In the present study, we examined the effects of Leo on action potentials and membrane currents recorded from isolated rat ventricular myocytes with the whole-cell patch clamp technique. Leo 100 µM shortened the action potential duration in a dose-dependent manner. Leo up to 200 µM had no significant effect on the Na+ current (INa) and K+ current (IK). However, Leo depressed the L-type Ca2+ current (ICa,L). In the presence of 20 and 100 µM Leo, the current density was decreased and the voltage at half maximal inactivation V0.5 shift to more negative potential. The recovery time constant was also delayed. In addition, the transcription and protein expression levels of L-type calcium channel (Cav1.2) in primary cultured neonatal myocytes from Sprague-Dawley rats were reduced by Leo treatment in a dose-dependent fashion as assessed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assays. We conclude that Leo inhibits L-type calcium channels in cardiomyocytes.

[Etiologic factors of erectile dysfunction in men with type 2 diabetes mellitus].

OBJECTIVE: To investigate the relationship of erectile dysfunction (ED) with blood vessel-, nerve- and androgen-related factors in young and middle-aged men with type 2 diabetes mellitus (T2DM) in order to provide some clinical evidence for early prevention and treatment of ED. METHODS: We divided 53 male T2DM patients under 50 years into an ED group (IIEF-5 score < or = 21, n = 28) and a non-ED (NED) group (IIEF-5 score > or = 22, n = 25). We detected the levels of blood lipid, glucose, total testosterone (TT), sex hormone-binding globulin (SHBG), sulfate dehydroepiandrosterone (DHEA-S), calculated free testosterone (cFT), and examined the complications of macroangiopathy (MA), diabetic retinopathy (DR) and diabetic peripheral neuropathy (DPN), and compared the above indicators between the two groups. RESULTS: There were no significant differences between the two groups in age, diabetes duration, body mass index, blood pressure, and blood lipid and glucose levels (P > 0.05). The incidence rate of DR was significantly higher in the ED than in the NED group (39.3% vs 4.0%, P < 0.05), but no statistically significant differences were found in the levels of TT, cFT, SHBG and DHEA-S and the incidence rates of MA and DPN between the two groups (P > 0.05). CONCLUSION: The incidence of ED is closely related to DR in young and middle-aged men with T2DM. Therefore particular attention should be paid to the erectile function of T2DM patients with DR as early as possible.

Body composition and risk of major gynecologic malignancies: Results from the UK Biobank prospective cohort.

OBJECTIVE: To evaluate the association between body composition and subsequent risk of the major gynecologic malignancies. METHODS: This is a prospective analysis of participants from the UK Biobank. We measured baseline body composition and confirmed cancer diagnosis through linkage to cancer and death registries. We evaluated hazard ratios (HRs) and confidence interval (CIs) with COX models adjusting for potential confounders. RESULTS: We document 1430 cases of the top three gynecologic malignancies (uterine corpus cancer 847 cases, ovarian cancer 514 cases, and cervical cancer 69 cases) from 245,084 female participants (75,307 were premenopausal and 169,777 were postmenopausal). For premenopausal women, whole body fat-free mass (WBFFM) was associated with an increased risk of uterine corpus cancer (Adjusted HR per unit increase 1.04, 95% CI 1.02-1.06). For postmenopausal women, compared with the first quartile, the fourth quartile of WBFFM and whole body fat mass(WBFM) was associated with 2.16 (95% CI 1.49-3.13) times and 1.89 (95% CI 1.31-2.72) times of increased uterine corpus cancer risk, respectively. Regarding the distribution of body fat mass (FM)/fat-free mass (FFM), FFM distributed in the trunk was associate with increased uterine corpus cancer risk in premenopausal (HR 1.18,95% CI 1.07-1.31) and postmenopausal women (HR 1.13,95% CI 1.09-1.18). Meanwhile, FM/FFM distributed in the limbs present an U-shaped associations with uterine corpus cancer risk. We did not observe any association between aforementioned body composition indices with ovarian or cervical cancer. CONCLUSION: FM is associated with an increased risk of uterine corpus cancer in postmenopausal women. Meanwhile, FFM is found to be a risk factor for uterine corpus cancer in both premenopausal and postmenopausal women. No association of body composition with ovarian or cervical cancer was observed.

Gut microbiota as a target for prevention and treatment of type 2 diabetes: Mechanisms and dietary natural products.

Type 2 diabetes mellitus (T2DM) is among the most remarkable public health concerns globally. Accumulating research evidence documents that alteration of gut microbiota has an indispensable role in the onset and progression of obesity and T2DM. A reduced microbial diversity is linked to insulin resistance and energy metabolism, especially for the rise of the Firmicutes/Bacteroidetes ratio. Changes in metabolites followed by the gut dysbacteriosis are linked to the presence of T2DM. Moreover, endotoxin leakage and gut permeability caused by gut dysbacteriosis is more of a trigger for the onset and progression of T2DM. Research documents that natural products are remarkable arsenals of bioactive agents for the discovery of anti-T2DM drugs. Many studies have elucidated that the possible mechanisms of the anti-T2DM effects of natural products are remarkably linked to its regulation on the composition of gut microflora and the successive changes in metabolites directly or indirectly. This review presents a brief overview of the gut microbiota in T2DM and several relevant mechanisms, including short-chain fatty acids, biosynthesis and metabolism of branched-chain fatty acids, trimethylamine N-oxide, bile acid signaling, endotoxin leakage, and gut permeability, and describes how dietary natural products can improve T2DM via the gut microbiota.

[The effects of glucose fluctuation on resistin].

OBJECTIVE: To explore the effect of glucose fluctuation on resistin. METHODS: The phorbol-12-myristate-13-acetate(PMA)-activated and differentiated U937 cells were exposed to experimental condition for 3 days, three groups of cells were formed, each one receiving the following fresh medium every 6 hours, respectively: (1) continuous 11.1 mmol/L glucose concentration medium (Con group), (2) continuous 22.2 mmol/L glucose concentration medium (CHG group), (3) alternating 11.1 mmol/L glucose concentration and 22.2 mmol/L glucose concentration medium every 6 hours (IHG group). The supernatants of cell median at the last 6 hours were collected to test resistin concentration. Besides, 92 subjects were selected and classified into three groups according to the results of oral glucose tolerance test: normal glucose tolerance group (NGT group, n=30), impaired glucose tolerance patients (IGT group, n=31) and newly diagnosed type 2 diabetes patients (T2DM group, n=31). Blood glucose and serum resistin levels were measured at 0 h and 1 h during oral glucose tolerance test (OGTT) to compare the glucose fluctuation (ΔGlu1-0) and the change of serum resistin level (ΔlnRes1-0) among the three groups. RESULTS: Resistin concentration in the Con, CHG and IHG group was (73.62±5.07) ng/L, (97.78±7.00) ng/L and (212.49±28.81) ng/L respectively and in IHG group it was higher as compared with the other two groups (P<0.05). ΔGlu1-0 in NGT, IGT and T2DM group was (2.31±2.30) mmol/L, (5.70±2.08) mmol/L and (8.41±2.63) mmol/L respectively; ΔGlu1-0 increased gradually in all the three groups (P<0.05). Serum resistin level from 0 h to 1 h in the NGT group was 6.41 (1.52-15.76) µg/L to 6.96 (1.52-22.70) µg/L, in the IGT group 5.47 (1.49-24.09) µg/L to 9.12 (1.27-21.94) µg/L and in the T2DM group 5.77 (1.11-30.10) µg/L to 9.27(1.02-48.15) µg/L. In the IGT and T2DM group serum resistin level increased from 0 h to 1 h (P<0.05), but no difference was observed in the NGT group (P>0.05). ΔlnRes1-0 in these 3 groups was (0.05±0.05) µg/L, (0.25±0.04) µg/L and (0.37±0.03) µg/L respectively and the change in the T2DM group was significant as compared with that in the NGT group, ΔlnRes1-0 was positively correlated with ΔGlu1-0 (r=0.23, P=0.02). CONCLUSION: Glucose fluctuation induced monocyte/macrophage to secrete resistin, greater the glucose fluctuation, greater the change of amplitude of serum resistin.

Sodium butyrate and dexamethasone promote exocrine pancreatic gene expression in mouse embryonic stem cells.

AIM: The feasibility of inducing endocrine pancreatic differentiation of embryonic stem (ES) cells has been well documented. However, whether ES cells possess the potential for exocrine pancreatic differentiation requires further exploration. Here, we investigated whether sodium butyrate and glucocorticoids were conducive to the exocrine pancreatic differentiation of ES cells. METHODS: E14 mouse ES cells were cultured in suspension to form embryoid bodies (EBs). These EBs were cultured in differentiating medium containing varying concentrations of sodium butyrate. The effects of activinA and dexamethasone (Dex) on exocrine differentiation were also explored. Finally, the combination of sodium butyrate, activinA, and Dex was used to promote the differentiation of exocrine pancreatic cells. Specific exocrine pancreatic gene expression was detected by reverse transcription polymerase chain reaction (RT-PCR) and amylase expression was examined by immunofluorescence staining. Flow cytometry analysis was also performed to determine the percentage of amylase-positive cells after the treatment with activinA, sodium butyrate, and Dex. RESULTS: Exposure of ES cells to 1 mmol/L sodium butyrate for 5 days promoted exocrine pancreatic gene expression. Further combination with Dex and other pancreatic-inducing factors, such as activinA, significantly enhanced the mRNA and protein levels of exocrine pancreatic markers. Additionally, flow cytometry revealed that approximately 17% of the final differentiated cells were amylase-positive. CONCLUSION: These data indicate that the exocrine pancreatic differentiation of ES cells can be induced by activinA, sodium butyrate, and Dex, providing a potential tool for studying pancreatic differentiation and pancreas-related diseases.

[Insulin resistance and islet beta cell function in type 2 diabetes mellitus and non alcoholic fatty liver disease.].

OBJECTIVE: To investigate insulin resistance and islet beta cell function in type 2 diabetes mellitus (T2DM) and non alcoholic fatty liver disease (NAFLD). METHODS: Two hundred and six study subjects were classified into 4 groups. Hepatic insulin resistance index (HIR), HOMA insulin resistance index (HOMA-IR) and Matsuda index (MSI) were used to assess insulin resistance. HOMA-beta, early and late phase indexes of insulin secretion were used to evaluate islet beta cell function. RESULTS: HIR in the NAFLD group and T2DM with NAFLD group were significantly higher than that in the control group and T2DM group (4.13 +/- 0.64, 4.03 +/- 0.69 vs 3.52 +/- 0.78, 3.53 +/- 0.64, P < 0.05), HOMA-IR in the T2DM with NAFLD group was significantly higher than that in the NAFLD group and T2DM group (3.35 +/- 2.69 vs 2.31 +/- 1.39, 2.40 +/- 1.55, P < 0.05). Early phase insulin secretion index in the NAFLD group was lower than that in the control group significantly (2.13 +/- 0.17 vs 2.61 +/- 0.13, P < 0.05), but there was no significant difference of HOMA-beta and late phase insulin secretion index between the NAFLD group and control group, HOMA-beta, early and late phase indexes of insulin secretion in the T2DM group and T2DM with NAFLD group were significantly lower than those in the control group. CONCLUSIONS: Normal glucose tolerance NAFLD patients may present with insulin resistance, mainly hepatic insulin resistance. Islet beta cell function in the NAFLD patients show damage of early phase insulin secretion. Newly diagnosed T2DM with or without NAFLD patients generally present with insulin resistance, early and later phase insulin secretion dysfunction. Insulin resistance in patients with T2DM and NAFLD is more severe.

Multicenter clinical study on the efficacy and safety of inhalable insulin aerosol in the treatment of type 2 diabetes.

BACKGROUND: A new inhalable insulin aerosol (Inh-Ins) was developed in China. The aim of this multicenter clinical study was to evaluate the efficacy and safety of this new Inh-Ins as a treatment of type 2 diabetes. Regular porcine insulin (RI) was used as a control. METHODS: This study is a prospective, randomized, open-label, parallel-group multicenter clinical trial in which 253 qualified patients with type 2 diabetes received the insulin Glargine daily at bedtime plus either a pre-meal Inh-Ins or a pre-meal subcutaneous RI for 12 weeks. HbA1c, fasting plasma glucose (FPG), the 1-hour-postprandial blood glucose (1hPBG) and the 2-hour-postprandial blood glucose (2hPBG) were measured. Events were monitored for adverse effects. RESULTS: After 12 weeks, the HbA1c decreased significantly from baseline in both treatment groups, with no significant difference between the two regimens. In the Inh-Ins group, FPG, both 1hPBG and 2hPBG significantly declined from baseline after the 8th- and 12th-weeks of treatment. The reduced values of FPG or 1hPBG between the two groups showed a more significant hypoglycemic effect with the Inh-Ins than the RI. After 12 weeks, the pulmonary carbon monoxide diffusing capacity (DLco) was significantly lower in Inh-Ins group than in the RI. The main side effects of Inh-Ins were coughing, excessive sputum, and hypoglycemia. CONCLUSIONS: Inh-Ins was effective in decreasing HbA1c like the RI. It was better in lowering the FPG and the 1hPBG than the RI. Its main side effects were coughing, excessive sputum, and hypoglycemia. Also, Inh-Ins slightly impaired DLco.

[The finite element analysis of stress distribution in different size of MO cavities restored with composite resin inlays].

PURPOSE: To explore the effect of different depth and width of meiso-occlusal (Class II) cavity type on the tooth tissue resistance stress after restoration with composite resin inlays. METHODS: The 3-D finite element model of mandibular first molar with meiso-occlusal (Class II) cavity restored with composite resin inlay was established by using CBCT scanning and reverse engineering software Mimics, Geomagic Studio, and finite element analysis software ANSYS. Comparative analysis of restoration with different depth and width meiso-occlusal (Class II) cavity under the same load of perpendicular and 45° deviation was explored, and finally the main stress and Von-mises stress changed as well as stress distribution were analyzed. RESULTS: The main stress was located in the gingival wall opposite to the inlay, while the major stress concentration area of the tooth was distributed near the canal at the bottom of the cavity. With the increase of the depth and width, the main stress and Von-mises stress distribution areas of tooth were getting larger. The Von-mises stress of tooth was influenced by the width variation of the cavity, while that depth change of cavity was affected by Von Mises stress of the inlay. CONCLUSIONS: With the increase of the depth and width of the cavity as well as lateral loading force, the peak stress of tooth with inlays increased and the distribution of stress concentration is modified after meiso-occlusal (Class II) cavity being inlayed with composite resin.

Effects of resistin on skeletal glucose metabolism.

Resistin is an adipokine highly related to insulin resistance (IR). The purpose of our research was to investigate how resistin influences skeletal glucose metabolism and explore its mechanisms. We constructed the recombinant plasmid pcDNA3.1 expressing resistin and then transfected it into C2C12 myocytes. The expression of resistin in C2C12 myocytes was detected by Western blotting. Glucose uptake was measured by 3H labeled glucose; glucose oxidation and glycogen synthesis was detected with 14C-labeled glucose. GLUT4 mRNA was measured by reverse transcription polymerase chain reaction (RT-PCR). We observed that resistin was expressed in transfected myocytes, and resistin decreased insulin induced glucose uptake rate by 28%-31% and inhibited the expression of GLUT4 mRNA. However, there was no significant difference in basal glucose uptake, and glucose oxidation and glycogen synthesis remained unchanged in all groups. It is concluded that resistin inhibits insulin induced glucose uptake in myocytes by downregulating the expression of GLUT4 and it has no effects on glucose oxidation and glycogen synthesis. Our findings may provide a clue to understand the roles of resistin in the pathogenesis of skeletal IR.

Effects of resistin expression on glucose metabolism and hepatic insulin resistance.

In order to observe the effect of increased serum resistin on glucose metabolism, insulin sensitivity, and hepatic insulin resistance (IR), mice were intravenously injected with recombinant adenovirus carrying the resistin gene (Adv-resistin-EGFP). Changes in hepatic glucose metabolism were observed using the Periodic Acid-Schiff method. Hepatic AMP-activated protein kinase (AMPK) activation was assessed by Western blot analysis, and glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was determined using real-time RT-PCR. Although no effect on fasting blood glucose was detected, increased fasting insulin levels, decreased glucose tolerance and insulin sensitivity, and reduced hepatic glycogen levels and AMPK activation were seen in the Adv-resistin-EGFP mice. Finally, elevated G6Pase and PEPCK mRNA expression levels were detected upon overexpression of resistin. Resistin may inhibit hepatic AMPK activity, which results in elevated expression of gluconeogenic enzymes thereby affecting glucose metabolism and leading to decreased glycogen storage that contributes to the development of hepatic IR.