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Early postoperative hyperglycemia in non-diabetic patients is an important risk factor affecting postoperative complications and mortality. This study aimed at investigating the effects of early postoperative hyperglycemia on postoperative complications, hospital costs, and length of hospital stay in non-diabetic patients with gastrointestinal malignancies; data of 1,015 non-diabetic patients with gastrointestinal malignancies, who underwent surgical intervention between January 2010 and January 2012, were retrospectively evaluated. Records on fasting plasma glucose (FPG), liver function, and kidney function were collected before and one day after surgery. Correlation of early postoperative FPG levels with postoperative complications, hospital costs, and length of hospital stay was further assessed in non-diabetic patients with gastrointestinal malignancies. One day after surgery, FPG results were significantly increased compared to preoperative values. FPG levels greater than or equal to 9.13 mmol/L (or 164.34 mg/dL) were associated with significant increases in the incidence of postoperative complications, length of hospital stay, and hospital costs. An association is shown between FPG and postoperative hyperglycemia in non-diabetic patients undergoing surgery for gastrointestinal malignancies. Significant increases in postoperative complications among these patients suggest that measurement of early postoperative FPG levels is critical to identify patients with postoperative hyperglycemia.

Chemerin is a newly discovered adipokine which has been found closely associated with obesity, metabolic syndrome (MetS), and inflammatory status. This study will investigate whether serum chemerin levels are associated with coronary artery disease (CAD) independently of other cardiovascular risk factors. This study included a total of 430 subjects (239 with CAD and 191 with non-CAD) who underwent coronary angiography. Anthropometric measurements were performed and chemerin, glucose, lipid profiles, and other biochemical characteristics were measured. The severity of coronary atherosclerosis was estimated by the total number of diseased vessels and Gensini score. Serum chemerin levels were significantly higher in the CAD group than in the non-CAD group (P = 0.011). The odds ratios (95% CI) of CAD across increasing quartiles of serum chemerin were 1.04 (0.61–1.78), 1.08 (0.63–1.83), and 1.87 (1.07–3.24), (P = 0.386, 0.508, and 0.012, respectively). Adjusting for age, sex, and other conventional risk factors for CAD did not appreciably alter the results. Serum chemerin levels were significantly increased with an increasing of number of diseased vessels (P = 0.024). In conditional linear regression models, chemerin levels were positively related to Gensini score even after established cardiovascular risk factors (β = 0.13, P = 0.019). Correlation analysis showed serum chemerin levels were significantly associated with TG levels, TC levels, fasting serum insulin, HOMA-IR and MetS (all P < 0.05). Higher serum chemerin levels were associated with increased risk of CAD and metabolic parameters in Chinese adults. Chemerin may represent a novel link between metabolic signals and atherosclerosis.

The aim of this article is to prospectively investigate the association of the liver enzyme γ-glutamyltransferase (GGT) with the development of diabetes and impaired glucose regulation (IGR) in a Chinese population. Seven hundred and sixty normoglycaemic subjects aged 40 years or older randomly selected from an urban community of Shanghai received a baseline investigation in May 2005. The participants were invited to receive a standard 75-g oral glucose tolerance test (OGTT) in November 2008. Incident diabetes and IGR were determined according to the 1999 WHO criteria. Serum GGT levels were significantly associated with incident diabetes or combined diabetes and IGR prospectively. After extensive adjustment, the diabetes risk was significantly increased with incrementing serum GGT quartiles (P value for trend = 0.0027). As compared with the lowest quartile of GGT, the highest quartile had an adjusted hazard ratio of 1.30 (95% CI 1.03-1.65) for developing combined diabetes and IGR. Furthermore, a high serum GGT level at baseline was independently associated with an increase in the index of homeostasis model assessment of insulin resistance (HOMA-IR) at follow-up. Serum GGT concentration, even within its normal range, is a risk marker for developing impaired glucose metabolism in middle-aged and elderly Chinese.

This study is to clarify whether C-reactive protein (CRP) and white blood cell (WBC) count influence insulin homeostasis to the same degree. Serum CRP and peripheral WBC were measured in 739 subjects with normal glucose regulation, 512 with impaired glucose regulation, and 502 newly diagnosed diabetic patients. Levels of insulin resistance (IR) were assessed using the index of homeostasis model (HOMA-IR). Serum CRP and WBC were significantly correlated with HOMA-IR and risk factors of IR. Relative risks of IR for each 1-SD increase of Ln (CRP) and Ln (WBC) were 1.28 (1.10-1.47) and 1.15 (1.01-1.31), respectively after adjustment for age, sex, obesity measurements, and other traditional risk factors. Additional adjustment for WBC slightly attenuated the association between CRP and IR [1.25 (1.08-1.45); P = 0.003] whereas adjustment for CRP substantially attenuated the association of WBC with IR toward null (P = 0.134). Moreover, individuals with both high levels of CRP and WBC were at higher risks of IR than those with high CRP or WBC alone. Both CRP and WBC were significantly associated with risks of IR. CRP might be a more effective biomarker in terms of the association with IR.

Adipokines produced from adipose tissues participate in regulation of reproduction, energy homeostasis, food intake, and neuroendocrine function in the hypothalamus. We have previously reported that adiponectin significantly reduced GnRH secretion from GT1-7 hypothalamic GnRH neuron cells. In this study, we further investigated the inhibition of GnRH secretion by adiponectin in vivo and found that extracellular signal-regulated kinase (ERK) was inhibited and AMPK activated. Furthermore, we found that activated AMPK by adiponectin reduced ERK phosphorylation, which possibly impaired GnRH secretion in GT1-7 cells.

Classical congenital adrenal hyperplasia (CAH) is characterized by the defects in cortisol and aldosterone secretion, and accompanied with adrenal hyperandrogenism. It is likely that the impaired adrenocortical function and intermittent treatment-related hypercortisolism may predispose patients to the development of metabolic syndrome in adulthood. Our aim was to assess the impact of hyperandrogenism on metabolic profiles in CAH women without glucocorticosteroid treatment. We evaluated the clinical characteristics and metabolic profiles in 30 untreated Chinese female adults with simple virilizing congenital adrenal hyperplasia (SV-CAH). Mutation analysis was performed by sequencing the entire 21-hydroxylase gene (CYP21A2). As compared with the controls, CAH patients had higher BMI (BMI, 21.5±2.1 vs. 20.0±1.8 kg/m2, P

An emerging concept suggests that an aberrant distributed body fat is closely linked to the occurrence of metabolic abnormalities. Mice deficient in steroid receptor coactivator-3 (SRC-3) are shown to be protected against high-fat diet (HFD) induced obesity but little is known about whether visceral (VAT) and subcutaneous adipose tissue (SCAT) distribute differently in SRC-3(-/-) mice versus SRC-3(+/+) mice. Here we reported that under HFD, fat redistributed between VAT and subcutaneous area of SRC-3(-/-) mice. When VAT/SCAT weight ratio (VAT/SCAT ratio) was calculated, SRC-3(-/-) mice had significantly elevated VAT/SCAT ratio in HFD versus normal diet (ND), while VAT/SCAT ratio was similar in SRC-3(+/+) mice under ND and HFD. Serological changes in SRC-3(-/-) mice paralleled the altered fat distribution. In SRC-3(-/-) mice, assays on gene expression revealed an increase in adipogenesis in VAT versus SCAT and an elevation in thermogenesis and lipolysis in SCAT versus VAT, which could explain the preferential fat accumulation in SRC-3(-/-) VAT. Our results presented in vivo evidence that SRC-3 deficiency could lead to fat redistribution under HFD in mice and provided new clues to researches on the pathogenesis of fat redistribution.

Thymic carcinoid is an important component of the tumor spectrum causing Ectopic ACTH Syndrome (EAS) and usually carries a poor prognosis. Efforts have been focused on exploring the mechanism of the excessive ACTH production in non-pituitary tumors, whereas few studies have reported the molecular events underlying the tumor progression. In this study, seven patients with ACTH producing thymic carcinoids were enrolled. Of note is that five of them showed either lymph node metastasis, local invasion or distant metastasis. By using cDNA profiling approach, we evaluated the expression of cell adhesion pathway genes and found a remarkable overexpression of p21-activated kinase 3 (PAK3) in all thymic carcinoids which was further confirmed at both transcriptional and translational level. RAC1, an upstream activator of PAK3, was also overexpressed in thymic carcinoids. Overexpression of PAK3 in NIH3T3 cell enhanced cell migration and invasion. Importantly, we observed c-Jun NH(2)-terminal kinase (JNK) was activated in PAK3 transfected cells, and inhibition of JNK activity by SP600125, a JNK pathway inhibitor, abolished PAK3 mediated cell migration. Activation of JNK pathway was also detected in thymic carcinoid with high level of PAK3 expression. Our findings suggested a potential role of PAK3 in the progression of ACTH-producing thymic carcinoid.

The purpose of this study is to find out whether the −607 C/A polymorphism in IL-18 gene promoter will affect serum IL-18 concentrations and glucose metabolism in Chinese subjects. In 232 patients with impaired glucose regulation (IGR) or type 2 diabetes and 212 subjects of normal glucose regulation (NGR), −607 C/A polymorphism was analyzed by polymerase chain reaction with sequence specific primers. Serum IL-18 concentrations were determined by ELISA in 200 subjects. Compared with subjects with NGR, those with type 2 diabetes and IGR had significant higher IL-18 concentrations [114.4 (92.9–149.2) and 102.1 (67.5–138.2) vs. 77.3 (53.8–107.8) pg/ml, P = 0.0026 and P

The objective is to evaluate the association of arterial stiffness [brachial-ankle pulse wave velocity (ba-PWV)] with glycemic control and duration of type 2 diabetes in diabetic subjects with or without hypertension. One thousand Chinese diabetic patients (562 with hypertension, 438 without hypertension) were included in this study. All patients underwent ba-PWV and biochemical measurements. Ba-PWV was significantly higher in diabetic subjects with hypertension than those without hypertension (1779 +/- 341 vs. 1691 +/- 342 cm/s, P0.0001), and these subjects were under similar glycemic control (6.9 +/- 1.5 vs. 6.9 +/- 1.3, P = 0.86). In diabetic and hypertensive subjects, ba-PWV was positively associated with HbA1c (1715 +/- 314 vs. 1851 +/- 335 cm/s, in subjects with HbA1c6.5% and with HbA1c7.0%, respectively, P0.0001), as well as duration of diabetes (1671 +/- 342 vs. 1791 +/- 313 vs. 1861 +/- 338 cm/s, in subjects with duration of diabetes5 years, 5-10 years, and10 years, respectively, P all0.05). In diabetic subjects without hypertension, ba-PWV was not associated with HbA1c (P = 0.47), but associated with duration of diabetes (1503 +/- 272 vs. 1692 +/- 354 cm/s, in subjects with duration of diabetes5 years and10 years, respectively, P = 0.0013). Ba-PWV was higher in diabetic subjects with hypertension than in diabetic subjects without hypertension, suggesting the independent effect of hypertension on arterial stiffness in diabetic subjects. Ba-PWV positively correlated with HbA1c and duration of diabetes in subjects with diabetes and hypertension, suggesting the importance of early glycemic control in the prevention of arterial stiffness and vascular complications.

Prader-Willi syndrome (PWS) is a complex, genetic, multisystem disorder. Its major clinical features include neonatal hypotonia and failure to thrive, mental retardation, hypogonadism, short hands and feet, hyperphagia-caused obesity, and characteristic appearance. The genetic basis of PWS is also complex. It is caused by the absence of expression of the active paternal genes such as the SNRPN, NDN, and possibly others in the PWS critical region on 15q11-13. PWS is in effect a contiguous gene syndrome resulting from deletion of the paternal copies of the imprinted. Consensus in clinical diagnostic criteria was established in 1993. However, identifying relevant patients for tests remains a challenge for most practitioners, as many features of the disorder are nonspecific, and others can be subtle or evolved over time. Consequently, molecular genetic tests can be used to diagnose PWS accurately, allowing early diagnosis of the syndrome. High resolution G-banding, high resolution cytogenetic methylation-specific PCR (MS-PCR), and fluorescence in situ hybridization (FISH) are routinely used to diagnose PWS. In this study, four Chinese patients, with typical PWS features, were detected by MS-PCR and FISH. Three were cytogenetically normal, but lacked paternal expression of proximal chromosome 15q because of maternal uniparental disomy (UPD). The other one, however, demonstrated an unbalanced de novo translocation 46, XX, t (7; 15).

Microalbuminuria is associated with higher cardiovascular mortality, especially in diabetics. But the direct association between microalbuminuria and vascular wall properties is still not clear. We investigated quantitative carotid stiffness (QCS) index in relation to microalbuminuria in 260 Chinese diabetic patients. In categorical analyses, patients with elevated urinary albumin-to-creatinine ratio (uACR) had higher QCS than those with normal uACR (P < 0.001). The corresponding values for QCS values were 4.4 and 5.9, respectively. In multiple stepwise regression analyses, QCS was significantly associated with age, uACR, plasma glycosylated hemoglobin A(1C) (HbA(1C)), and current smoking (P < 0.05 for all). In conclusion, carotid stiffness as measured by QCS, a local functional measurement of the arterial wall, is increased in type 2 diabetes with microalbuminuria.

Glucagon-like peptide-1 (7-36) amide (GLP-1) is an insulin secretagogue. Recently, many studies have shown GLP-1 can improve insulin resistance in peripheral tissues. In the present study, we investigated glucose uptake in 3T3-L1 adipocytes in either basal or insulin resistant state and dissected insulin signaling pathway in order to elucidate the molecular mechanisms of GLP-1 mediated improvement of insulin resistance. We found GLP-1 and its long lasting analogue, exendin 4 up-regulated basal IR, IRS-1 and Glut 4 expressions although they did not increase basal glucose uptake alone. However, GLP-1 and exendin-4 increased insulin mediated glucose uptake in intact and TNF-alpha treated 3T3-L1 adipocytes by up-regulation of phophorylated IRbeta, IRS-1, Akt and GSK-3beta. These results indicate that GLP-1 and its analogue exendin-4 can amplify insulin signaling in 3T3-L1 adipocytes by up-regulation of some crucial insulin signaling molecules.

Type 2 diabetes mellitus (T2DM) is a heterogeneous disorder characterized by defects in insulin secretion and action and obesity plays an important role in the deterioration of glucose metabolism. In the present study we evaluated the degree of insulin resistance and first-phase insulin secretion of beta-cell in obese subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM in Chinese. A total of 220 subjects underwent standard 75 g oral glucose tolerance test (OGTT) and insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity index (S I) was assessed by the reduced sample number (n = 12) of Bergman's minimal model method with FSIGT. Insulin secretion capacities were determined by the insulinogenic index (I 30 min - I 0 min)/(G 30 min - G 0 min) in OGTT and the acute insulin response to glucose (AIR) in FSIGT. The disposition index (DI), the product of AIR and S I was used to determine whether AIR was adequate to compensate for insulin resistance. The S I in healthy lean control group was significantly higher than that in NGT, IGT, and T2DM group, but there was no significant difference among NGT, IGT, and T2DM group. The AIR in NGT group was significantly greater than that in control group, but then it was progressively decreased in IGT and T2DM group. The value of DI in control group was significantly higher than that in those three abnormal groups, and was decreased from NGT to IGT and T2DM group with significant difference. It indicates that obese subjects with different glucose tolerances have a similar degree of insulin resistance but differ in insulin secretion in Chinese Han population.

Beta cell replication is the major component for maintenance of beta cell mass in adult rodents; however, little is known about what is the earliest signals that initiate rodent beta cell proliferation. The mTORC1 pathway integrates signals from growth factors and nutrients and regulates cell growth and survival. Here, we used normoglycemic 60 % partial-pancreatectomy (60 % Px) mouse model to determine whether mTORC1 pathway was required for compensatory beta cell proliferation. C57BL/6 J male mice were subjected to 60 % Px or sham operation, and subsequently treated with either rapamycin or vehicle for 7 days. Metabolic profile, pancreatic beta cell mass, and proliferation were examined, and expression levels of cell cycle regulators were determined. Beta cell proliferation was increased by 2.5-fold, and mTORC1 signaling was activated in islets post-Px. Rapamycin treatment impaired glucose tolerance and glucose stimulating insulin secretion in 60 % Px mice, but did not affect their insulin sensitivity in peripheral tissue. Rapamycin inhibited mTORC1 activity in beta cells, suppressed compensatory beta cell proliferation and growth, and reduced beta cell mass and insulin content in 60 % Px mice. Px caused an increase of the cyclin D2 at protein level and promoted cyclin D2 nuclear localization in an mTOR-dependent manner. Disrupting mTORC1 signaling suppressed cell proliferation and simultaneously diminished cyclin D2 protein abundance in RINm5F cells. Our data demonstrated that mTORC1 plays an essential role in beta cell adaption to significant beta cell mass loss in 60 % Px model and in early compensatory beta cell proliferation via cyclin D2 pathway.

Liddle's syndrome has been known as a disorder associated with abnormal sodium reabsorption in the distal tubule and transmitted as a rare autosomal dominant trait. It is caused by mutations in the SCNN1B or SCNN1C gene, which truncate the cytoplasmic carboxyl terminus of the beta and gamma subunit of the epithelial sodium channel (ENaC). Genetic analysis of ENaC in a Chinese family with Liddle's syndrome revealed P616H of SCNN1B coaggregated with the phenotype, while this variant was not detected in 100 unrelated subjects. No mutation at gamma ENaC could be detected in all members of the family. P616H is located in the conserved proline-rich PY motif of the betaENaC. The PY motif can interact with the WW domain in Nedd4 and affect the activity of ENaC. Structural bioinformatics analysis confirmed that the functional interaction between Nedd4 and ENaC reduces in Liddle-ENaC (P616H) when compared with wild-type ENaC. In summary, P616H may be an underlying mechanism for the signs and symptoms of this family.

This study is to prospectively investigate the association between serum uric acid and the incidence of type 2 diabetes in middle-aged and elderly Chinese. This study consisted of 924 non-diabetic adults aged 40 years or older at baseline. Subjects who received antidiabetic therapies and those who responded positively to the 75-g oral glucose tolerance test according to the 1999 World Health Organization criteria were diagnosed as having type 2 diabetes. Ninety-eight subjects developed type 2 diabetes during the 3.5-year follow-up. The hazard ratio (HR) for incident diabetes was 1.50 [95% confidence interval (CI) 1.18–1.92] for the highest sex-specific quartile of serum uric acid compared with the lowest after controlling for confounders. Participants with hyperuricemia had an HR of 1.95 (95% CI 1.11–3.44) for incident diabetes compared with those without hyperuricemia. Compared with the lowest quartile, the highest quartile had an HR for incident diabetes of 2.45 (95% CI 1.39–4.33) in men and 1.39 (95% CI 1.04–1.84) in women after fully adjustment. Adding serum uric acid to a model of conventional risk factors for diabetes improved the area under the curve for prediction of type 2 diabetes by 5%. Serum uric acid was an independent predictor of incident type 2 diabetes in middle-aged and elderly Chinese.

Variations in the fat mass and obesity-associated (FTO) gene have recently been associated with obesity and type 2 diabetes mellitus among different ethnic populations. Given that the phenotype of polycystic ovary syndrome (PCOS) overlaps with obesity and type 2 diabetes, we hypothesize that the common rs9939609 variant of FTO gene is related to PCOS susceptibility. We performed a case–control association study on 215 women with PCOS, using 227 healthy women as the control. We examined the association between rs9939609 variant and PCOS susceptibility, as well as between PCOS and obesity-related parameters in Chinese women. We observed significant differences in the allelic and genotypic distributions between PCOS patients and the control group. The A allele was significantly more frequent among PCOS patients than in the control population (15.1% vs. 9.9%; A allele vs. T allele, OR = 1.62, P = 0.019). The A allele carrier genotype (AA and AT) frequencies were also significantly greater in PCOS patients than in the controls (28% vs. 19%; AT and TT vs. TT genotype, OR = 1·61, P = 0.035). In logistic regression, the strength of this association was attenuated after adjustment for body mass index (BMI) (A allele vs. T allele, OR = 1.39, P = 0.286; AT and TT genotypes vs. TT genotype, OR = 1.40, P = 0.312). However, we did not find any significant associations of rs9939609 variant with obesity-related traits. In conclusions, the rs9939609 variant in the FTO gene is associated with PCOS susceptibility in the Chinese population, probably because of its effect on BMI.

The clinical use of criteria for metabolic syndrome (MetS) and its individual components with respect to risk prediction of coronary heart disease (CHD) remains uncertain. In this study, we investigated whether and to what extent MetS and its individual components were related to risk for CHD. A total of 1,028 subjects, who had undergone coronary angiography or were diagnosed as acute myocardial infarction, were selected according to inclusion criteria. MetS was diagnosed with National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) criteria. CHD was diagnosed with clinical data and confirmed by coronary angiography. The severity of coronary atherosclerosis was estimated by CHD Gensini cumulative index. All the patients were aged 33-87 years. The results showed that the age- and sex-adjusted odds ratios (ORs) for CHD in different individual components of MetS were as follows: low-high density lipoprotein (low-HDL), 3.15 (1.94-5.12); high-fasting plasma glucose (high-FPG), 2.26 (1.63-3.69); high-blood pressure (high-BP), 2.13 (1.38-3.29); high-triglycerides (high-TG), 1.55 (1.13-2.11); all P0.05, whereas high-body mass index (high-BMI), 0.75 (0.55-1.03) and high-waist circumference, 0.75 (0.51-1.10), both P0.05. Among all the components, the triad of low-HDL, high-FPG, and high-BP had the highest OR for CHD: 4.28 (3.12-5.87) (P0.001). MetS subjects had significant increases in number of disease vessel and CHD Gensini index (P0.001). When individual components of MetS were considered separately, groups with low-HDL, or high-FPG, or high-BP had significant increases in number of disease vessel and Gensini index (all P0.001). In conclusion, our present results demonstrated that individual components of MetS and their various combinations may have different contributions to CHD and the severity of coronary artery stenosis. Clinical focus should remain on establishing optimum-risk algorithms for CHD.

Pseudohypoparathyroidism (PHP) is a heterogeneous group of diseases characterized by hormone resistance to receptors that stimulate adenylate cyclase. PHP-Ia patients show specific Gs-alpha protein deficiency, PTH/TSH/gonadotropin resistance, and a phenotype characterized by Albright hereditary osteodystrophy (AHO). Many heterozygous mutations in the GNAS gene encoding the Gs protein have been identified in PHP-Ia. We describe two boys with hypocalcemia and elevated serum levels of PTH in a Chinese family. The 13 exons of the GNAS gene were amplified using 15 pairs of GNAS-specific primers and analyzed by direct sequencing. We found a novel frame shift mutation in exon 11 of the GNAS gene identified in both of the two boys and their mother. This report provides another example of a Gs-alpha mutation leading to PHP.

The purpose of this study was to investigate insulin sensitivity and first-phase insulin secretion in obesity with hyperglycemia in 30 and/or 60 min during oral glucose tolerance (OGTT, glucoseor = 11.1 mmol/l, post-loading hyperglycemia, PLH) in Chinese population. A total of 196 nondiabetic subjects were included in the present study, among them 99 had normal glucose tolerance (NGT, subdivided into 32 lean NGT and 67 obese NGT), 74 had obesity with impaired glucose tolerance (IGT) and 23 had obesity with PLH. A standard 75-g oral glucose tolerance test was performed after fasting and at 30 min, 1, 2 and 3 h. Insulin sensitivity index (S(I)) was assessed by the Bergman's minimal model method with frequently sampled intravenous glucose tolerance test (FSIGTT), insulin secretion was determined by acute insulin response to glucose (AIRg). The disposition index (DI), the product of AIRg and S(I) was used to determine whether AIRg was adequate to compensate for insulin resistance. S(I) was significantly equally lower in three obese subgroups. AIRg was significantly increased in obese NGT as compared with lean NGT controls, and reduced to the same extent in IGT and PLH subjects. There was no significant difference among lean NGT, IGT and PLH subjects. DI value was reduced from obese NGT individuals, IGT and PLH subjects had a similar lower level of DI. In conclusion, our present results demonstrated that the pathophysiological basis of obese subjects with PLH were clearly insulin resistance and defective in first-phase insulin secretion as that in IGT subjects in Chinese population.

In order to characterize the potential causative effects of interleukin-18 (IL-18) on insulin resistance, we measured glucose uptake in 3T3-L1 adipocytes treated with mouse recombinant IL-18. IL-18 surprisingly enhanced, rather than reduced insulin-mediated glucose uptake in adipocytes. Moreover IL-18 could counteract the glucose uptake suppression caused by tumor necrosis factor alpha in 3T3-L1 adipocytes. The mechanism dissection showed that the IL-18 upregulated phosphorylated Akt and downregulated phosphorylated P38 MAPK. These findings indicated that the elevated serum IL-18 levels in obesity and diabetes might be a compensatory response to insulin resistance.

Hereditary fructose intolerance (HFI) is an inheritable disorder of fructose metabolism, inherited as an autosomal recessive disorder and caused by catalytic deficiency of aldolase B, which is critical for gluconeogenesis and fructose metabolism. The affected individuals develop severe hypoglycemia after taking foods containing fructose and cognate sugars. The exons 2–9 of the aldolase B (gene symbol ALDOB) gene from one Chinese HFI patient were amplified by the polymerase chain reaction (PCR), and direct sequence determination was applied to the amplified fragments. The mutation of a 4-bp (AACA) deletion (479_482 del) in exon 4 of ALDOB gene was identified in the patient, which had been reported to cause a frameshift at codon 118 and a truncated protein of 132 amino acids in the previous study. Then, the second case with the same homozygote deletion and eight cases with heterozygotes had been found through screening for the mutation c.479_482 del AACA in the whole family. This is the first report of HFI with the mutation c.479_482 del AACA in the ALDOB gene in a Chinese family.

We investigated carotid intima-media thickness (IMT) and quantitative carotid stiffness (QCS) index in relation to plasma glycosylated hemoglobin A(1C) (HbA(1C)) and duration of diabetes mellitus in 337 Chinese diabetic patients. In categorical analyses, carotid IMT was 710 mum in subjects with a duration of diabetes mellitusor = 2 years, 760 micorm in subjects with a duration of diabetes mellitus more than two years and with plasma HbA(1C)6.5% (P0.05), and 790 microm in subjects with a duration of diabetes mellitus more than two years but with plasma HbA(1C)or = 6.5% (P0.01). The corresponding values for QCS values were 4.5, 4.6 and 5.1 (P0.05), respectively. In multiple stepwise regression analyses carotid IMT was significantly associated with the duration of diabetes mellitus, systolic blood pressure and serum concentration of total cholesterol, whereas QCS was significantly associated with age, HbA(1C), systolic and diastolic blood pressure (P0.05). In conclusion, carotid IMT as a structural measure of arterial wall is increased in patients with a longer history of diabetes mellitus, whereas QCS as functional index is mainly influenced by the quality of blood glucose control.

Adiponectin plays an important role in improving insulin resistance and preventing atherosclerosis. However it has been rarely reported that adiponectin influences insulin secretion because its receptor was identified in human islet beta cells. In order to investigate the direct effect of adiponectin on pancreatic islet beta cells, we performed an insulin secretion test in purified rat islets, which were incubated with adiponectin (100 ng/mL) at low (3.3 mM) and high (16.7 mM) glucose concentrations. Furthermore, cell lysates were extracted from the adiponectin-treated islets for p-AMPKalpha assay. RTPCR and immunohistochemical examination showed both adiponectin receptor 1 (AdipoR1) and receptor 2 (AdipoR2) were expressed in islet cells and AdipoR1 was predominantly expressed. Insulin secretion was significantly increased in the presence of adiponectin for 6 h at high glucose concentration. Meanwhile, the levels of phosphorylated AMPK increased with adiponectin treatment at high glucose concentrations. It is concluded that adiponectin augments insulin secretion from pancreatic islet beta cells at high glucose concentration through AMPK activation.

Overproduction of proinflammatory factors is associated with obesity and diabetes. Interleukin (IL)-18 as a member of IL-1 cytokine family is increased in obese, in diabetic, and even in polycystic ovary syndrome (PCOS) patients. In the present study we evaluated the association of serum IL-18 levels with insulin resistance in PCOS women. Forty-two PCOS women and 38 control subjects were enrolled in this study and matched with respect to age and body mass index (BMI). Serum IL-18 levels and hormones were measured for all subjects. Furthermore, euglycemic hyperinsulinemic clamp test was performed in selected 30 PCOS women and 11 control subjects. Serum IL-18 levels were elevated in PCOS women compared with the control (p = 0.033). IL-18 levels were positively correlated with homeostasis model assessment index (HOMA) beta index, which assesses beta cell function (p = 0.035), but were inversely correlated with clamp indices, which best represent insulin resistance status: M, Clamp ISI*100, and MCRg values (p = 0.006, 0.010, and 0.009 respectively). No correlation was found between IL-18 and age, BMI, waist-to-hip ratio (WHR), lipid profile, dehydroepiandrosterone-sulfate (DHEAS), sex hormone- binding globulin (SHBG), or fasting insulin levels. In conclusion, in the present study, serum IL-18 levels were significantly increased in PCOS women and firmly associated with insulin resistance displayed by euglycemic hyperinsulinemic clamp test. It indicates that IL-18 may be a contributing factor linking inflammation and insulin resistance in PCOS women.

Our previous work has described the gene expression patterns of human visceral adipose tissue (VAT) at the transcriptome level and reported that the strongly expressed genes in VAT showed an uneven distribution throughout the genome. The aim of the present work was to focus on the unclassified genes and known expressed sequence tags (ESTs) strongly expressed in VAT and analyze their structure and function with bioinformatics. Among the 400 ESTs strongly expressed in the VAT, 340 clones were classified into known genes through searching the latest Genbank database. Functional classification showed that 85 clones were unclassified known genes, and approx 90% of them were found to be expressed in adipose tissue for the first time. Among the 85 unclassified genes, only two share similarities in the coding sequences with all species examined, and six genes had so far no obvious similarity to any genes across different species. The protein products of 7 genes had putative signal peptide and 11 had transmembrane domains. The protein products of 39 genes had relative specific motifs or prosites on primary structure. In silico Northern blot showed that 21 known ESTs were abundantly specifically expressed in adipose tissue, which may provide clues to identify novel genes closely related to adipocyte function with potential pathophysiological implications.

McCune-Albright syndrome (MAS) is a sporadic disorder characterized by the classic triad of polyostotic fibrous dysplasia, café-au-lait' skin pigmentation, and hyperfunctional endocrinopathy. It is caused by embryonic somatic mutations leading to the substitution of His or Cys for Arg at amino acid 201 of the alpha-subunit of the signal transduction protein Gs (Gsalpha). A 32-year-old man was diagnosed as McCune-Albright syndrome with the following findings: polyostotic fibrous dysplasia, café-au-lait' spots and acromegaly. An ultrasonic examination showed that he had left-pleural effusion, which disappeared after almost a year without special treatment. Genomic DNA was isolated from the peripheral blood, bone tissue, skin lesion and pleura samples of the patient. Then PCR and direct sequencing were performed. An activating mutation of the Gsalpha gene (Arg201Cys) was found in the genomic DNA isolated from the peripheral blood and the bone tissue, but not in genomic DNA isolated from the skin and pleura samples.