A pilot study suggests that the G/G genotype of resistin single nucleotide polymorphism at -420 may be an independent predictor of a reduction in fasting plasma glucose and insulin resistance by pioglitazone in type 2 diabetes.

The aim of this study was to determine the relation between the G/G genotype of a resistin gene promoter single nucleotide polymorphism (SNP) at -420 (rs1862513) and glycemic control by pioglitazone in type 2 diabetes. In Study 1, 121 type 2 diabetic patients were treated with pioglitazone (15 or 30 mg/day) for 12 weeks, in addition to previous medication. In Study 2, 63 patients who had been treated with pioglitazone for 12 weeks were examined retrospectively. In Study 1, multiple regression analysis revealed that the G/G but not C/G genotype was correlated with a reduction in fasting plasma glucose (FPG) and homeostasis model assessment of insulin resistance (HOMA-IR) compared to C/C. When adjusted for age, gender, and BMI, the G/G genotype was an independent factor for the reduction of FPG (P=0.020) and HOMA-IR (P =0.012). When studies 1 and 2 were combined by adjusting the studies, age, gender, and BMI, the reduction of HbA1c was correlated with the G/G genotype (beta=-0.511, P=0.044). Therefore, this pilot study suggests that the G/G genotype of resistin SNP -420 may be an independent predictor of the reduction of fasting plasma glucose and HOMA-IR by pioglitazone.

Hyperresistinemia is associated with coexistence of hypertension and type 2 diabetes.

Numerous studies have demonstrated that high blood pressure substantially increases the risk of microvascular and macrovascular complications in patients with type 2 diabetes mellitus (T2DM). Currently, we found that serum resistin, an adipocyte- and monocyte-derived cytokine, was positively correlated with several components of the metabolic syndrome, including hypertension in T2DM. To investigate the association of resistin with an etiologic difference among subjects with hypertension with T2DM, hypertension without T2DM, and normotensive T2DM, we analyzed 210 subjects, including 91 with hypertension with T2DM, 55 with hypertension without T2DM, and 64 with normotensive T2DM. Serum resistin level was higher in subjects with hypertension with T2DM, followed by subjects with normotensive T2DM and hypertension without T2DM, irrespective of antihypertensive treatment status (20.9+/-17.6 and 14.0+/-8.9 versus 11.2+/-7.6 ng/mL, respectively; P<0.01). Simple regression analysis revealed that resistin positively correlated with blood pressure (systolic blood pressure: r=0.29, P<0.01; diastolic blood pressure: r=0.21, P<0.05) and intima-media thickness (r=0.27; P<0.05) in patients with T2DM but not in subjects with hypertension without T2DM. Multiple regression analysis, adjusted for age, gender, body mass index, fasting glucose, high-density lipoprotein cholesterol, white blood cell counts, and glomerular filtration rate, further revealed that resistin was an independent factor for high blood pressure in patients with T2DM (P<0.05). In vitro gene expression analysis in human coronary endothelial cells revealed that resistin induced fatty acid binding protein, a key molecule of insulin resistance, diabetes, and atherosclerosis. These results suggest that hyperresistinemia would contribute to the pathogenesis of hypertension in patients with T2DM, significantly linked to vascular complications and cardiovascular events.

Serum resistin is reduced by glucose and meal loading in healthy human subjects.

Resistin is an adipokine that induces insulin resistance in mice; serum concentrations are decreased by fasting and increased by feeding. Adiponectin, another adipokine, improves insulin sensitivity. The aims of this study were to determine the effects of glucose and meal loading on serum resistin and total and high-molecular weight (HMW) adiponectin in humans and to explore potential determinants of fasting serum resistin and of changes in resistin. Serum resistin and total and HMW adiponectin were measured by enzyme-linked immunosorbent assay in young, lean, nondiabetic subjects during 75-g oral glucose tolerance test (OGTT) and meal tolerance test (MTT). Resistin single nucleotide polymorphism (SNP) -420 was typed. Serum resistin was decreased at 60 and 120 minutes during OGTT compared with baseline (n = 36, 1-way repeated-measures analysis of variance, P < .0001; Scheffe, P = .0457 and P < .0001, respectively). Serum resistin was also reduced at 240 minutes during MTT (n = 33, 1-way repeated measures analysis of variance, P < .0001; Scheffe, P = .0002). Multiple regression analysis adjusted for age, sex, and body mass index revealed that the reductions in serum resistin were dependent on baseline resistin levels. Subjects with greater baseline concentrations of resistin experienced more pronounced declines in resistin (OGTT, unstandardized regression coefficient (beta) = -0.19, P = .0005; MTT, beta = -0.63, P < .0001). Serum total and HMW adiponectin was unchanged. Fasting serum resistin was positively correlated with the G allele number of SNP -420 (beta = 7.70, P = .01) and white blood cell count (beta = 0.007, P = .0001) adjusted for age, sex, and body mass index. Therefore, in young, lean, nondiabetic humans, serum resistin was reduced by glucose and meal loading; the reduction in resistin was greater in subjects with higher fasting resistin. Fasting resistin was correlated with SNP -420 and white blood cell count.

Serum resistin is positively correlated with the accumulation of metabolic syndrome factors in type 2 diabetes.

OBJECTIVE: Resistin, secreted from adipocytes, causes insulin resistance in rodents. We reported that the G/G genotype of a resistin gene promoter single nucleotide polymorphism (SNP) at -420 increases type 2 diabetes (T2DM) susceptibility by enhancing promoter activity. We also showed that serum resistin was positively correlated with G at SNP-420, the duration of T2DM, and HbA1c in T2DM. The aim of this study was to determine the relation between serum resistin and factors related to the metabolic syndrome (MetS) in T2DM. DESIGN, PATIENTS AND MEASUREMENTS: We analysed 238 Japanese T2DM subjects (124 males and 114 females, age 60.2 +/- 11.3 years, body mass index (BMI) 24.1 +/- 3.9) whose overnight fasting sera were available. Serum resistin was measured using ELISA. RESULTS: Serum resistin was higher in subjects with either obesity (P = 0.041), low HDL (P = 0.004), high triglycerides (TG) (P = 0.019), hypertension (HT) (P = 0.001) or atherosclerosis (P = 0.012). Simple regression analysis revealed that serum resistin was correlated with lower HDL, TG and high-sensitivity C-reactive protein (hsCRP). Multiple regression analysis (or logistic regression analysis for HT), adjusted for age, gender, BMI and the duration of T2DM, revealed that serum resistin was correlated with lower HDL (P = 0.008), TG (P = 0.041), HT (P = 0.031) and hsCRP (P = 0.004). Serum resistin was positively correlated with the number of MetS factors, independent of age, gender and the duration of T2DM (P < 0.001). Adjustment by either thiazolidinedione (TZD) treatment or hsCRP had no effects on these findings. CONCLUSIONS: Serum resistin was positively correlated with the accumulation of MetS factors in T2DM.

Comparison of clinical features and patient background in functional dyspepsia and peptic ulcer.

To elucidate the clinical features of functional dyspepsia (FD), patients with FD were compared with patients with peptic ulcer. Fifty-eight FD and fifty-nine peptic ulcer patients were compared with respect to clinical features and patient background. In the FD group, symptoms of dyspepsia, especially upper abdominal fullness and nausea, were more common than in the peptic ulcer group. The FD group complained greater distress (severity of the most distressing symptom; P < .001) and showed higher State-Trait Anxiety Inventory (STAI) scores (trait-anxiety score; P < .05). A higher proportion of FD patients had consulted another physician (P < .01). Even when subjects from the FD and peptic ulcer group in this study were matched for age and gender and compared with respect to these variables, almost the same characteristics were seen. These results indicate that FD markedly decreases quality of life in a variety of aspects.

Serum resistin is associated with the severity of microangiopathies in type 2 diabetes.

Resistin, secreted from adipocytes, causes insulin resistance and diabetes in rodents. To determine the relation between serum resistin and diabetic microangiopathies in humans, we analyzed 238 Japanese T2DM subjects. Mean serum resistin was higher in subjects with either advanced retinopathy (preproliferative or proliferative) (P=0.0130), advanced nephropathy (stage III or IV) (P=0.0151), or neuropathy (P=0.0013). Simple regression analysis showed that serum resistin was positively correlated with retinopathy stage (P=0.0212), nephropathy stage (P=0.0052), and neuropathy (P=0.0013). Multiple regression analysis adjusted for age, gender, and BMI, revealed that serum resistin was correlated with retinopathy stage (P=0.0144), nephropathy stage (P=0.0111), and neuropathy (P=0.0053). Serum resistin was positively correlated with the number of advanced microangiopathies, independent of age, gender, BMI, and either the duration of T2DM (P=0.0318) or serum creatinine (P=0.0092). Therefore, serum resistin was positively correlated with the severity of microangiopathies in T2DM.

Resistin SNP-420 determines its monocyte mRNA and serum levels inducing type 2 diabetes.

Resistin, secreted from adipocytes, causes insulin resistance in rodents. Its roles and main source in humans remain unknown. The G/G genotype of resistin single nucleotide polymorphism, SNP-420, induces type 2 diabetes mellitus (T2DM) by increasing promoter activity. We elucidated factors correlated with serum resistin and effects of SNP-420 on monocyte resistin mRNA. In 198 T2DM and 157 controls, fasting serum resistin was higher in T2DM. Multiple regression analysis revealed that SNP-420 genotype was the strongest determinant of serum resistin. In T2DM, 1-year duration of T2DM and 1% HbA1c was also correlated with 0.19 and 0.54 ng/ml serum resistin, respectively. Logistic regression analysis revealed that serum resistin was an independent factor for T2DM. In 23 healthy volunteers, monocyte resistin mRNA was positively correlated with its simultaneous serum levels and was higher in G/G genotype. Thus, SNP-420 determines monocyte mRNA and serum levels of resistin, which could induce T2DM.

cAMP-pKA signaling regulates multiple steps of fungal infection cooperatively with Cmk1 MAP kinase in Colletotrichum lagenarium.

In Colletotrichum lagenarium, RPK1 encoding the regulatory subunit of PKA is required for pathogenicity. From the rpkl mutant that forms small colonies, we isolated three growth-suppressor mutants. All rpk1-suppressor mutants are nonpathogenic and contain amino acid changes in the PKA catalytic subunit Cpkl. To assess the roles of cyclic AMP (cAMP) signaling in detail, we generated knockout mutants of CPK1 and the adenylate cyclase gene CAC1. The cpk1 and cac1 mutants are nonpathogenic on cucumber. Interestingly, both of the mutants germinated poorly, suggesting involvement of cAMP signaling in germination. Germination defect in the cpk1 and cac1 mutants is partially rescued by incubation of the conidia at lower concentrations. Germinating conidia of the cpk1 and cac1 mutants can form appressoria, but the appressoria formed by them are nonfunctional, like those of the rpk1 mutant. Cytological analysis indicates that the appressoria of the cpk1 mutant contain larger numbers of lipid bodies compared with the wild type, whereas lipid levels in the rpk1 mutants are lower, suggesting cAMP-mediated regulation of lipid metabolism for appressorium functionality. Furthermore, the cpk1 and cacl mutants have a defect in infectious growth in plant. In C. lagenarium, Cmkl mitogen-activated protein kinase (MAPK) regulates germination, appressorium formation, and infectious growth. These results suggest that cAMP signaling controls multiple steps of fungal infection in cooperative regulation with Cmkl MAPK in C. lagenarium.