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• The pH dependence of the casein micelle was investigated using SAXS and USAXS. • SAXS profiles were analyzed using a structure model including water domains. • The size of a micelle and CCP were changed in response to changes in pH. • pH affected the voluminosity and other physical properties in a micelle. • The structure of the casein micelles varied sensitively with pH changes. Changes in milk pH significantly influence the behavior and physical properties of casein micelles; however, the effects of these changes on casein micelle structures are still unclear. The aim of this study was to elucidate the effect of changes in pH range from 5.9 to 7.1 on the structure of casein micelles in milk using small-angle X-ray scattering (SAXS) and ultra small-angle X-ray scattering (USAXS). The casein micelles formed one-dimensional aggregates. The micelle radius decreased with decreasing pH, whereas the size of the water domain increased. The distance between colloidal calcium phosphates (CCP) remained unchanged, whereas the CCP radius decreased with decreasing pH. Voluminosity, which was calculated from scattering intensities, increased at increased pH. In conclusion, the micelle structure changed significantly in response to changes in pH. Our findings help to understand the changes in the physical properties of milk at various pH levels in terms of the microscopic structure. [ABSTRACT FROM AUTHOR]

• The temperature-dependence of the casein micelle was investigated by in-situ SAXS. • SAXS profiles were analyzed using a structure model including water domains. • Inner structure of casein micelles varied sensitively with temperature changes. • The structure changes were thermoreversible. Milk is used and processed under various environmental temperature, and its physicochemical properties are also strongly affected by temperature. Therefore, it is important to reveal the structure of milk at variable temperatures. In this study, the temperature dependence of the inner structure of bovine casein micelles in the temperature range of 10–40 °C was investigated by in-situ small-angle X-ray scattering (SAXS) method. The micelle size calculated from the SAXS profiles using a micelle model including water domains was almost independent of temperature. The water domain expanded and the distance between the colloidal calcium phosphates (CCP) decreased with increasing temperature. The number of CCPs in a micelle increased, because CCPs were newly formed by the transfer of calcium and inorganic phosphate from serum into the micelle. These structural changes occurred during the cooling process. Therefore, in the temperature range of 10–40 °C, the structure of the casein micelle varied sensitively with the temperature, and these structural changes were thermoreversible in nature. [ABSTRACT FROM AUTHOR]

Low serum adiponectin is associated with a high incidence of type 2 diabetes or coronary artery disease in the general population. Paradoxically, serum adiponectin is elevated in patients with chronic kidney disease (CKD), such as overt diabetic nephropathy. The current study aimed to investigate whether anemia was independently associated with the serum level of high-molecular-weight (HMW) adiponectin in patients with type 2 diabetes. We studied 207 type 2 diabetic patients (92 women and 115 men). Anemia was defined as a hemoglobin (Hb) <13.0g/dL in men and <12.0g/dL in women according to the guidelines of the World Health Organization (WHO). Overt nephropathy (CKD) was defined as clinical proteinuria and /or estimated glomerular filtration rate (eGFR) lower than 60mL/min for more than 3 months. The diabetic patients were divided into 4 groups according to the presence or absence of anemia and/or CKD. Serum HMW adiponectin levels were measured by a sandwich enzyme-linked immunosorbent assay. In all 207 patients with type 2 diabetes, serum total and HMW adiponectin levels were correlated positively with age, the duration of diabetes, high-density lipoprotein (HDL) cholesterol, urinary albumin, and serum erythropoietin, whereas negative correlations were found with body mass index, triglyceride, eGFR, Hb, hematocrit, and high sensitivity C-reactive protein. A stepwise regression analysis demonstrated that among several significant variables, Hb had the strongest independent influence on HMW adiponectin (β =−0.487, P < 0.001). Diabetic patients of both sexes with anemia and CKD had the highest serum levels of HMW adiponectin among the 4 groups. In conclusion, anemia is associated with marked elevation of serum HMW adiponectin levels in diabetic patients who have CKD, and this elevation is independent of renal function. [Copyright &y& Elsevier]

Abstract: Adiponectin exists in the blood as 3 forms, which are a trimer, a hexamer, and a high–molecular weight (HMW) form. We investigated whether circulating HMW adiponectin levels were altered by oral glucose or fat ingestion. Forty male subjects underwent a 75-g oral glucose loading test (OGTT), and 11 healthy subjects (5 women and 6 men) received a fat loading test. Serum levels of HMW and total adiponectin were measured during the OGTT and the fat loading test. The fat loading test was performed for at least 8 hours. Among the 40 male subjects, 11 had normal glucose tolerance (NGT), 9 had impaired fasting glucose (IFG), 11 had impaired glucose tolerance, and 9 had diabetes mellitus (DM). In all 40 subjects, the serum total adiponectin level did not change significantly, whereas serum HMW adiponectin decreased significantly after a glucose load and reached 92.2% of the basal level at 120 minutes after the OGTT (P < .01). The HMW to total adiponectin ratio decreased significantly from 0.47 ± 0.15 at baseline to 0.43 ± 0.13 at 120 minutes after a glucose load (P < .05). Serum HMW adiponectin measured at 120 minutes after the OGTT decreased significantly to 86.0% and 85.6% of the basal level in subjects with NGT or IFG, respectively (both P < .01). In subjects with impaired glucose tolerance or DM, however, serum HMW adiponectin did not change. The area under the curve for insulin at 30 minutes after a glucose load during the OGTT was significantly larger in subjects with NGT or IFG than in those with DM (P < .05). In addition, the insulinogenic index (ΔI 0-30/ΔG 0-30) was significantly higher in subjects with NGT or IFG than in those with DM (P < .001). Percentage changes in serum HMW adiponectin of the baseline at 120 minutes correlated negatively with those in serum insulin (r = −0.468, P = .0023), but not plasma glucose, of the baseline at 30 minutes in 40 subjects. On the other hand, serum triglycerides increased significantly after an oral fat load in 11 healthy subjects; but neither serum total nor HMW adiponectin changed. In conclusion, serum HMW adiponectin (but not total adiponectin) decreased rapidly after glucose loading in subjects with NGT or IFG; and the decrease of HMW adiponectin may be associated with an increase of serum insulin at 30 minutes. [Copyright &y& Elsevier]

Abstract: High–molecular weight (HMW) adiponectin may have the most biologic activity among several isoforms. We investigated long-term effects of losartan on serum concentrations of total and HMW adiponectin in hypertensive patients with metabolic syndrome (MS) by serial measurements over 6 months. Forty hypertensive patients first received 50 mg of losartan. Upward titration of the losartan dose was implemented to reach a target blood pressure of less than 140/90 mm Hg. Serum total adiponectin and HMW adiponectin were measured at study entry (baseline), the 3-month treatment time point, and the end of the 6-month period. Non-HMW adiponectin (ie, medium– and low–molecular weight adiponectin) was calculated as total adiponectin − HMW adiponectin. Diagnosis of MS was done by current standard criteria. In hypertensive patients without MS (n = 21), the serum total adiponectin increased from 9.8 ± 5.4 μg/mL at baseline to 11.1 ± 6.2 μg/mL at 6 months (P < .01). Furthermore, the serum total adiponectin was significantly higher at 6 months than at 3 months (P < .01). Serum HMW adiponectin also increased from 5.7 ± 3.9 μg/mL at baseline to 6.6 ± 4.4 μg/mL at 6 months (P < .01). In hypertensive patients with MS, the serum total adiponectin increased from 6.0 ± 2.7 μg/mL at baseline to 6.7 ± 3.3 μg/mL at 3 months and to 7.0 ± 3.1 μg/mL at 6 months (P < .01 for both). Furthermore, the serum HMW adiponectin concentration was significantly higher at 6 months than at 3 months (P < .001). However, the serum non-HMW adiponectin concentration did not change during treatment in either group. In conclusion, serum total and HMW adiponectin concentrations increase after 6 months of losartan treatment in hypertensive patients, irrespective of the presence or absence of MS. [Copyright &y& Elsevier]

Abstract: Sympathetic activation is associated with metabolic syndrome (MS) and increased risk of cardiovascular disease. The aim of this study was to investigate whether cardiac autonomic activity or sympathovagal balance, as estimated by a 24-hour power spectral analysis of heart rate variation, is associated with serum concentrations of high-sensitivity C-reactive protein (hs-CRP), a sensitive predictor for cardiovascular events, in type 2 diabetic patients with and without MS. We studied 104 type 2 diabetic patients (50 female and 54 male). The diagnosis of MS was based on the National Cholesterol Education Program Adult Treatment Panel III criteria. Based on the serum hs-CRP, diabetic patients were also divided into 3 groups: low risk (CRP < 1.0 mg/L), moderate risk (1.0 ≤ CRP ≤ 3.0), and high risk (CRP > 3.0). Heart rate variation was determined automatically every 5 minutes over 24 hours using an ambulatory Holter electrocardiographic recording. Power spectral analysis of the R-R intervals was performed by fast Fourier transformation. Low frequency (LF, both sympathetic and parasympathetic activities), high frequency (HF, pure parasympathetic activity), and the ratio of LF to HF, an index of sympathovagal balance, were used as indices of cardiac autonomic activity. Blood concentrations of hs-CRP, interleukin 6, and plasminogen activator inhibitor 1 were higher in diabetic patients with than in those without MS (P < .0001, P = .0056, and P < .0001, respectively). Both the 24-hour mean LF and the LF-to-HF ratio were also significantly higher in diabetic patients with than in those without MS (P = .0397 and P = .0483, respectively). The LF-to-HF ratio at 6:00 am was significantly higher in diabetic patients with a high CRP concentration than in those with a low or moderate CRP concentration (P < .001 and P < .01, respectively). Only urinary albumin and hs-CRP were independent factors predicting the LF-to-HF ratio at 6:00 am in diabetic patients. In conclusion, type 2 diabetic patients with MS have elevated markers of inflammation and evidence of cardiac sympathetic predominance. High serum concentrations of hs-CRP are associated with relative cardiac sympathetic overactivity during the early morning in type 2 diabetic patients. [Copyright &y& Elsevier]

Abstract: We investigated the effects of low-dose pioglitazone (7.5mg/day) on serum high molecular weight (HMW) adiponectin and fluid retention (estimated from hematocrit) in 14 male and 16 female patients with type 2 diabetes. All of them were being treated with sulfonylureas and had poor glycemic control. Patients were given 7.5mg/day of pioglitazone and were followed for 12 weeks at monthly intervals. In all 30 patients, HbA1c was significantly decreased after 12 weeks of treatment with pioglitazone (8.2±0.7% vs. 7.4±0.8%, P <0.0001). Serum HMW adiponectin increased markedly from 5.2 (2.4, 8.6)μg/ml at baseline to 9.8 (4.1, 12.6)μg/ml at the end of pioglitazone treatment (P <0.0001). When the changes were evaluated separately for each sex, diabetic men showed no increase of body weight or BMI after treatment, while HbA1c decreased significantly, and did Hct. Serum HMW adiponectin increased significantly after treatment. In diabetic women, neither body weight nor BMI increased after treatment with pioglitazone, as was the case for the men. HbA1c decreased significantly, and did Hct. Serum HMW adiponectin increased significantly after treatment. In conclusion, low-dose pioglitazone therapy could significantly improved glycemic control and markedly increased serum HMW adiponectin in both male and female Japanese patients with type 2 diabetes. [Copyright &y& Elsevier]