Objective: Arabinoxylan (AX) consumption is associated with metabolic improvement during diabetes and with modulation of ghrelin, an orexigenic gut hormone. The effect of AX consumption on ghrelin secretion in disturbed metabolic states is unknown. Therefore, we investigated the postprandial responses to AX consumption of serum glucose, insulin and triglycerides and plasma total and acylated ghrelin in subjects with impaired glucose tolerance (IGT). Design: Randomized, single-blind, controlled, crossover intervention trial. Subjects: Seven female and four male adults with IGT, aged 55.5 years, and body mass index (BMI) 30.1 kg/m 2 . Intervention: Subjects received either placebo or 15 g AX supplement for 6 weeks with a 6-week washout period in-between. Main outcome measurements: Postprandial responses of serum glucose, insulin and triglycerides, and plasma total and acylated ghrelin after a liquid meal challenge test (LMCT) measured at the beginning and at the end of the dietary intervention at À20, À5, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min. Results: After LMCT, AX consumption resulted in lower postprandial responses in serum glucose, insulin and triglycerides (Po0.05). Compared to placebo, total plasma ghrelin was also reduced by 4278 pg/ml (Po0.001) after AX consumption with no difference in plasma acylated ghrelin. Conclusion: AX consumption improved postprandial metabolic responses after an LMCT in subjects with IGT and reduced total ghrelin response. However, acylated ghrelin responses were unchanged, suggesting that the acylated ghrelin-mediated orexigenic regulation is not improved as only total plasma ghrelin decreased. Sponsorship: Federal Ministry of Education and Research Germany (PTJ-BIO/0313042C).
Ghrelin is an orexigenic hormone that may affect substrate utilization in humans. Ghrelin is influenced by macronutrients, but the effects of insoluble dietary fiber and polyphenols are unknown. We investigated the effects of a polyphenol-rich insoluble dietary fiber preparation from carob pulp (carob fiber) on postprandial ghrelin responses and substrate utilization. Dose-dependent effects of the consumption of carob fiber were investigated in a randomized, single-blind, crossover study in 20 healthy subjects, aged 22-62 y. Plasma total and acylated ghrelin, triglycerides, and serum insulin and nonesterified fatty acids (NEFA) levels were repeatedly assessed before and after ingestion of an isocaloric standardized liquid meal with 0, 5, 10, or 20 g of carob fiber over a 300-min period. The respiratory quotient (RQ) was determined after consumption of 0 or 20 g of carob fiber. Carob fiber intake lowered acylated ghrelin to 49.1%, triglycerides to 97.2%, and NEFA to 67.2% compared with the control meal (P < 0.001). Total ghrelin and insulin concentrations were not affected by consumption of a carob fiber-enriched liquid meal. Postprandial energy expenditure was increased by 42.3% and RQ was reduced by 99.9% after a liquid meal with carob fiber compared with a control meal (P < 0.001). We showed that the consumption of a carob pulp preparation, an insoluble dietary fiber rich in polyphenols, decreases postprandial responses of acylated ghrelin, triglycerides, and NEFA and alters RQ, suggesting a change toward increased fatty acid oxidation. These results indicate that carob fiber might exert beneficial effects in energy intake and body weight.
The consumption of arabinoxylan, a soluble fibre fraction, has been shown to improve glycemic control in type 2 diabetic subjects. Soluble dietary fibre may modulate gastrointestinal or adipose tissue hormones regulating food intake. The present study investigated the effects of arabinoxylan consumption on serum glucose, insulin, lipids, leptin, adiponectin and resistin in subjects with impaired glucose tolerance. In a randomized, single-blind, controlled, crossover intervention trial, 11 adults consumed white bread rolls as either placebo or supplemented with 15 g arabinoxylan for 6 weeks with a 6-week washout period. Fasting serum glucose, insulin, triglycerides, unesterified fatty acids, apolipoprotein A1 and B, adiponectin, resistin and leptin were assessed before and after intervention. Fasting serum glucose, serum triglycerides and apolipoprotein A-1 were significantly lower during arabinoxylan consumption compared to placebo (p=0.029, p=0.047; p=0.029, respectively). No effects of arabinoxylan were observed for insulin, adiponectin, leptin and resistin as well as for apolipoprotein B, and unesterified fatty acids. In conclusion, the consumption of AX in subjects with impaired glucose tolerance improved fasting serum glucose, and triglycerides. However, this beneficial effect was not accompanied by changes in fasting adipokine concentrations.
The effects of the novel calpain inhibitor A-705239 were studied in isolated perfused rabbit hearts subjected to 45 min of global ischemia, followed by 60 min of reperfusion. During 15 min of perfusion the inhibitor accumulated in myocardial tissue up to 16 times the concentration in the perfusate. Almost complete recovery and survival of heart function (90%) was seen with an inhibitor concentration of 10(-8) M in the perfusion fluid when the compound was administered prior to ischemia. Left ventricular pressure amplitude and coronary flow showed significantly higher values during reperfusion in the presence of the inhibitor. A-705239 significantly reduced the release of creatine kinase, from 166+/-49 U/l in untreated hearts to 44+/-10 U/l, and diminished the release of lactate dehydrogenase from 118+/-20 U/l in untreated hearts to 63+/-4 U/l. Mitochondrial dysfunction following ischemia and reperfusion was markedly attenuated by the inhibitor. Thus, the state 3 respiration rate only decreased to 4.2 in contrast to 2.6 nmol O2/(min x mg s.w.) in untreated hearts, reflecting a reduced damage of oxidative phosphorylation. Furthermore, in the presence of the inhibitor the inner mitochondrial membranes became less permeable as indicated by a smaller leak respiration. The excellent properties of A-705239 should make this compound a valuable tool for further pharmacological studies.
We have recently shown that a polyphenol-rich insoluble dietary fibre preparation from carob pulp (Ceratonia siliqua L; carob fibre) decreased postprandial acylated ghrelin, TAG and NEFA during an acute liquid meal challenge test. However, delayed effects of carob fibre consumption are unknown. Therefore, a randomized controlled crossover study in nineteen healthy volunteers consuming foods with or without 50 g carob fibre was conducted. On the subsequent day (day 2), glucose, TAG, total and acylated ghrelin as well as insulin, NEFA and leptin were assessed at baseline and at timed intervals for 300 min after ingestion of standardized bread. Consumption of carob fibre-enriched foods did not affect fasting concentrations of glucose, TAG, total ghrelin, NEFA, insulin and leptin. Fasting acylated ghrelin was increased on the day subsequent to carob fibre consumption compared with control (P¼0·046). After consumption of the standard bread on day 2, glucose response (P¼ 0·029) was increased, and TAG (P¼0·033) and NEFA (P,0·001) responses were decreased compared with control. Postprandial responses of total and acylated ghrelin, insulin and leptin on day 2 were unaffected by carob fibre consumption the previous day. In conclusion, an increase in total and acylated plasma ghrelin accompanied by enhanced lipid metabolism after carob fibre consumption suggests higher lipid utilization and suppressed lipolysis on the day subsequent to carob fibre consumption. However, elevated glucose levels after carob fibre consumption need to be addressed in future studies.Carob: Insoluble dietary fibre: Polyphenols: Glucose: Insulin: Ghrelin Epidemiological studies clearly show that a high intake of insoluble fibre is associated with a low risk for CVD and diabetes 1 -3 . Beneficial effects of insoluble dietary fibre are also discussed in the context of consumption of whole grain, containing further bioactive compounds such as polyphenols, antioxidants or vitamins. As another potential mechanism for the beneficial effects of dietary fibre, fermentation processes in the colon are discussed resulting in the production of SCFA 4,5 . Polyphenols have been shown to reduce food intake, to lower leptin concentrations 6 and to promote fat oxidation in rats 7 . Recently, we showed that the consumption of a polyphenol-rich insoluble dietary fibre preparation from carob pulp (Ceratonia siliqua L; carob fibre) acutely decreased postprandial TAG and NEFA concentrations, while increasing fat oxidation during a liquid meal challenge test 8 . Elevated circulating TAG and NEFA play a key role in the development of insulin resistance 9 . Impaired whole body insulin resistance is characterized by a lowered ability of skeletal muscle to oxidize fatty acids 9 . Therefore, functional foods lowering circulating NEFA by increasing fat oxidation might be of interest for the prevention and treatment of diabetes and obesity.Obesity is the result of a positive energy balance. Among peripheral hormones regulating energy balance, the orexigenic ghrelin and the ano...
Two novel calpain inhibitors (A-705239 and A-705253) were studied in isolated perfused rabbit hearts subjected to 60-min occlusion of the ramus interventricularis of the left coronary artery (below the origin of the first diagonal branch), followed by 120 min of reperfusion. The inhibitors were added to the perfusion fluid in various final concentrations from the beginning of the experiments before the coronary artery was blocked. Hemodynamic monitoring and biochemical analysis of perfusion fluid from the coronary outflow were carried out. Myocardial infarct size and the area at risk (transiently non-perfused myocardium) were determined from left ventricular slices after a special staining procedure with Evans blue and 2,3,5-triphenyltetrazolium chloride. The infarcted area (dead myocardium) was 77.9"2.3% of the area at risk in untreated controls (ns12). The infarct size was significantly reduced in the presence of both calpain inhibitors. The best effect was achieved with 10 -8 M A-705253 (ns8), which reduced (p-0.001) the infarcted area to 49.3"3.9% of the area at risk, corresponding to an infarct reduction of 61.8%. No statistical difference was observed between the experimental groups in coronary perfusion, left ventricular pressure, and in the release of lactate dehydrogenase and creatine kinase from heart muscle.
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