Co-ingestion of a protein hydrolysate and amino acid mixture with carbohydrate improves plasma glucose disposal in patients with type 2 diabetes. (49/260)

BACKGROUND: Although insulin secretion after carbohydrate ingestion is severely impaired in patients with type 2 diabetes, amino acid and protein co-ingestion can substantially increase plasma insulin responses. OBJECTIVE: We investigated insulin responses and the subsequent plasma glucose disposal rates after the ingestion of carbohydrate alone (CHO) or with a protein hydrolysate and amino acid mixture (CHO+PRO) in patients with a long-term diagnosis of type 2 diabetes. DESIGN: Ten type 2 diabetic patients [mean (+/-SEM) age: 62 +/- 2 y; body mass index (kg/m(2)): 27 +/- 1] and 9 healthy control subjects (age: 58 +/- 1 y; body mass index: 27 +/- 1) participated in 2 trials in which the plasma insulin response was measured after the ingestion of 0.7 g carbohydrate . kg(-1) . h(-1) with or without 0.35 g . kg(-1) . h(-1) of a mixture that contained a protein hydrolysate, leucine, and phenylalanine. Continuous infusions with [6,6-(2)H(2)]glucose were then given to investigate plasma glucose disposal. RESULTS: Plasma insulin responses were higher by 299 +/- 64% and 132 +/- 63% in the CHO+PRO trial than in the CHO trial in the diabetic patients and the matched control subjects, respectively (P < 0.001). The subsequent plasma glucose responses were reduced by 28 +/- 6% and 33 +/- 3% in the CHO+PRO trial than in the CHO trial in the diabetic patients and the matched control subjects, respectively (P < 0.001). The reduced plasma glucose response in the diabetic patients was attributed to a 13 +/- 3% increase in glucose disposal (P < 0.01). CONCLUSIONS: The combined ingestion of carbohydrate with a protein hydrolysate and amino acid mixture significantly increases de novo insulin production in patients with a long-term diagnosis of type 2 diabetes. The increased insulin response stimulates plasma glucose disposal and reduces postprandial glucose concentrations.  (+info)

Pharmacoproteomic effects of isoniazid, ethambutol, and N-geranyl-N'-(2-adamantyl)ethane-1,2-diamine (SQ109) on Mycobacterium tuberculosis H37Rv. (50/260)

The present study was aimed at fingerprinting pharmacoproteomic alterations of the Mycobacterium tuberculosis H37Rv strain induced by antitubercular drugs isoniazid (INH), ethambutol (EMB), and SQ109 [N-geranyl-N'-(2-adamantyl)ethane-1,2-diamine, a novel 1,2-diamine-based EMB analog], providing new understanding of pharmacoproteomic mechanisms of each and exploring new drug targets. The three drugs produced significant down-regulation of 13 proteins, including immunogenic ModD, Mpt64, with proteins from the Pro-Glu family being inhibited the most. Alternatively, the three drugs up-regulated 17 proteins, including secreted antigenic proteins ESAT-6 and CFP-10. Among these, ESAT-6 and AphC were most affected by INH, whereas EMB had the greatest effect on ESAT-6. All three drugs produced only moderate up-regulation of aerobic and iron metabolism proteins, i.e., electron transfer flavoprotein Fix A and Fix B, and ferritin-like protein BfrB, suggesting that the interruption of microbacterial energy metabolism is not a primary mechanism of action. INH suppressed ATP-dependent DNA/RNA helicase, but up-regulated beta-ketoacyl-acyl carrier protein synthase. These effects may contribute to its bactericidal effects. In contrast, EMB and SQ109 did just the opposite: these drugs up-regulated the helicase and down-regulated the synthase. For most of the H37Rv proteins, similar pharmacoproteomic patterns were found for both EMB and SQ109. None of the drugs significantly regulated expression of chaperonins GroES, GroEL2, and Dnak, suggesting that these drugs do not affect chaperone-mediated nascent polypeptide folding and sorting. The present study identified proteins directly modulated by the actions of INH, EMB, and SQ109 and distinguished INH activity from the diamine antitubercular compounds that inhibit M. tuberculosis H37Rv.  (+info)

Formation of biocompatible nanoparticles by self-assembly of enzymatic hydrolysates of chitosan and carboxymethyl cellulose. (51/260)

A simple preparation method for biocompatible nanoparticles in high concentration (0.5 wt %) by self-assembly of chitosan and carboxymethyl cellulose hydrolysates was developed. Chitosan and carboxymethyl cellulose were hydrolyzed beforehand with chitosanase and cellulase respectively to make fragments having lower molecular weights. Nanoparticles were spontaneously formed only by mixing the two hydrolysate solutions. The particle size distribution was relatively narrow, about 200 nm in mean size. The mean particle size decreased from 226 nm to 165 nm with decreasing molecular weight of chitosan hydrolysate from 9.5 to 6.8 kDa. The mixing ratio of chitosan and carboxymethyl cellulose hydrolysates also affected particle size. Changes in particle size are discussed in relation to a possible mechanism of polyionic complexation. The chitosan-carboxymethyl cellulose nanoparticles were stably suspended over 1 week even under low pH (pH 3.0), high ionic strength (NaCl 1 M), or low temperature (4 degrees C) conditions.  (+info)

Identification of 9-hydroxyoctadecadienoic acid and other oxidized free fatty acids as ligands of the G protein-coupled receptor G2A. (52/260)

G2A is a G protein-coupled receptor that is predominantly expressed in lymphoid tissues and macrophages. G2A can be induced by diverse stimuli to cause cell cycle arrest in the G(2)/M phase in pro-B and T cells. G2A is also expressed in macrophages within atherosclerotic lesions, suggesting G2A involvement in atherosclerosis. Recently, G2A was discovered to possess proton-sensing ability. In this paper, we report another function of G2A, that is, as a receptor for 9-hydroxyoctadecadienoic acid (9-HODE) and other oxidized free fatty acids. G2A, expressed in CHO-K1 or HEK293 cells, showed 9-HODE-induced intracellular calcium mobilization, inositol phosphate accumulation, inhibition of cAMP accumulation, [(35)S]guanosine 5'-3-O-(thio)triphosphate binding, and MAP kinase activation. Furthermore, G2A was activated by various oxidized derivatives of linoleic and arachidonic acids, but it was weakly activated by cholesteryl-9-HODE. Oxidized phosphatidylcholine (1-palmitoyl-2-linoleoyl) when hydrolyzed with phospholipase A(2) also evoked intracellular calcium mobilization in G2A-expressing cells. These results indicate that G2A is activated by oxidized free fatty acids produced by oxidation and subsequent hydrolysis of phosphatidylcholine or cholesteryl linoleate. Thus, G2A might have a biological role in diverse pathological conditions including atherosclerosis.  (+info)

Effect of intraperitoneally administered hydrolyzed whey protein on blood pressure and renal sodium handling in awake spontaneously hypertensive rats. (53/260)

The present study evaluated the acute effect of the intraperitoneal (ip) administration of a whey protein hydrolysate (WPH) on systolic arterial blood pressure (SBP) and renal sodium handling by conscious spontaneously hypertensive rats (SHR). The ip administration of WPH in a volume of 1 ml dose-dependently lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M NaCl: 188.5 +/- 9.3 mmHg vs WPH: 176.6 +/- 4.9 mmHg, N = 8, P = 0.001) and 1.0 g/kg (0.15 M NaCl: 188.5 +/- 9.3 mmHg vs WPH: 163.8 +/- 5.9 mmHg, N = 8, P = 0.0018). Creatinine clearance decreased significantly (P = 0.0084) in the WPH-treated group (326 +/- 67 microL min-1 100 g body weight-1) compared to 0.15 M NaCl-treated (890 +/- 26 microL min-1 100 g body weight-1) and captopril-treated (903 +/- 72 microL min-1 100 g body weight-1) rats. The ip administration of 1.0 g WPH/kg also decreased fractional sodium excretion to 0.021 +/- 0.019% compared to 0.126 +/- 0.041 and 0.66 +/- 0.015% in 0.15 M NaCl and captopril-treated rats, respectively (P = 0.033). Similarly, the fractional potassium excretion in WPH-treated rats (0.25 +/- 0.05%) was significantly lower (P = 0.0063) than in control (0.91 +/- 0.15%) and captopril-treated rats (1.24 +/- 0.30%), respectively. The present study shows a decreased SBP in SHR after the administration of WPH associated with a rise in tubule sodium reabsorption despite an angiotensin I-converting enzyme (ACE)-inhibiting in vitro activity (IC50 = 0.68 mg/mL). The present findings suggest a pathway involving ACE inhibition but measurements of plasma ACE activity and angiotensin II levels are needed to support this suggestion.  (+info)

A parallel approach to post source decay MALDI-TOF analysis. (54/260)

We present a novel enhancement to matrix-assisted laser desorption ionization (MALDI) post-source decay (PSD) analysis whereby fragment ions from multiple precursor ions are acquired into the same spectrum without employing a timed ion gate to preselect each parent ion. Fragment ions are matched to their corresponding precursor ions by comparing spectra acquired at slightly different reflectron electric fields. By measuring the difference in time-of-flight (TOF) between the two spectra for each fragment, it is possible to calculate the mass of the fragment ion and its parent. This new "parallel PSD" technique reduces analysis time and consumes less sample than conventional PSD, which requires an ion gate for serial preselection of precursor ions.  (+info)

Effect of wheat gluten hydrolysate on the immune system in healthy human subjects. (55/260)

Nine healthy volunteers were divided into a test group (n = 5) and a control group (n = 4). The test group consumed 3 grams per d of wheat gluten hydrolysate for 6 d, and their NK cell activity and hematological parameters were measured: The same assessments were performed in the control group, which did not receive wheat gluten hydrolysate. In the test group, NK cell activity increased significantly (P = 0.018) after wheat gluten hydrolysate intake. No adverse effects were observed in either group.  (+info)

Virion polypeptide composition of the human papovavirus BK: comparison with simian virus 40 and polyoma virus. (56/260)

The polypeptide composition of labeled BK virus was compared with that of simian virus 40 (SV40) and polyoma virus by co-electrophoresis of disrupted virions in polyacrylamide gels containing approximately 73% of the capsid protein and had a molecular weight of 39,000. It was smaller than VP1 of SV40 and polyoma virus. The other polypeptides of BK virus were similar in molecular weight to those of SV40. A comparison of the proteins of BK virus and SV40 iodinated with chloramine T before and after disruption in alkaline buffer at pH 10.5 revealed differences between the two viruses in the number and distribution of tyrosines available for iodination. The tryptic peptides of VP1, VP3, VP4, and VP5 combined of SV40 were compared with those of the same polypeptides of BK virus. Among the 19 peptides of VP1 resolved, only two were common to both viruses. The analyses of VP4 and VP5, the histone-like proteins, however, showed more similarity between the viruses, with 6 of 15 resolved peptides in common. The tryptic digests of VP3 were completely different.  (+info)