The secretion of insulin from the pancreatic β-cell must be commensurate to satisfy the insulin requirements of the organism. This cell has a great flexibility to meet these requirements which are increased not only by the ingestion of nutrients (increase of plasma glucose) but also by the sensitivity of target tissues to insulin as well. The insulin secretion is a complex biochemical event regulated by a host of potential second messenger molecules acting alone or in concert. These events include the cation calcium, which gains access to the β-cell via the opening of voltage-regulated channels, cAMP and phosphoinositide-derived second messenger molecules, generated as a consequence of phospholipase C (PLC) activation. In this review, we focused on phosphoinositides, PLC/Phosphokinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) cascade in the regulation of insulin secretion. We also described our studies on the mechanism of the β-cell desensitization using perifused islets. It is suggested that a failure of the signaling events contribute to the pathogenesis of diabetes in which the β-cell can no longer secrete the required amounts of insulin. It has been observed that chronic exposure to high glucose desensitizes the β-cells to subsequent stimulation. We suggested that the failure of PLC activation can be attributed in the impairment of insulin secretion by chronic sustained glucose exposure. It may contribute to the vicious circle of impaired insulin secretion leading up to diabetes.
Thiamin (vitamin B1) is known to activate carbohydrate metabolism in part through activation of pyruvate dehydrogenase. The purpose of this study was to investigate the effect of thiamin tetrahydrofurfuryl disulfide (TTFD), a thiamin derivative, on utilization of exogenous glucose by measuring oxidation of 13C-glucose at rest and during prolonged exercise in mice under normal dietary conditions. Mice orally ingested TTFD (0.1 mg/g BW [body weight]) and 13C-glucose (0.8 mg/g BW) or 13C-lactate (0.1 mg/g BW) plus glucose (0.8 mg/g BW) at rest or before endurance running. The average percent of 13C atoms in total 12C+13C (13C atom%) in expired air after ingestion of 13C-glucose at rest was significantly lower in the TTFD group than in the control group. No significant difference was found in 13C atom% in expired air after ingestion of 13C-glucose and prolonged exercise. In addition, no significant effect of TTFD was found in expired 13C atom% after ingestion of 13C-lactate plus glucose at rest. TTFD also had no effect on concentrations of muscle or liver glycogen at rest. These results suggest that TTFD, which is a thiamin derivative, decreases oxidation of exogenous glucose at rest, but not during exercise.
The purpose of this study is to examine the relationship between dietary algae (seaweed) consumption and the risk of Type 2 diabetes mellitus in the Korean population. We analyzed data from the Korean National Health and Nutrition Examination Survey in 2005, a nationally representative survey. The study participants included 3,405 males and females aged 20-65 y. Participants were classified into four groups according to the quartiles of total algae consumption frequencies. Proportional odds models were used to assess the relationship between algae consumption and the risk of having diabetes or prediabetes, after adjustment for age, family history of diabetes, education, smoking, alcohol consumption, physical activity, body mass index, waist circumference, triglycerides, total energy intake and food group intakes. The frequency of algae consumption was positively correlated to the consumption of legumes, fruits, fish, and dairy products in both genders (p<0.001). The odds ratios (95% confidence interval) for diabetes vs. prediabetes vs. normoglycemia was 0.66 (0.43-0.99) for males and 0.80 (0.51-1.24) for females in the highest quartile of algae consumption compared to the lowest quartile. Our results suggest that dietary algae consumption may decrease the risk of diabetes mellitus in Korean men. A well-designed prospective study is needed to confirm this association.
Recent studies showed that the urinary excretion of the water-soluble vitamins can be useful as a nutritional index. To determine how fasting affects urinary excretion of water-soluble vitamins, a human study and an animal experiment were conducted. In the human study, the 24-h urinary excretion of water-soluble vitamins in 12 healthy Japanese adults fasting for a day was measured. One-day fasting drastically decreased urinary thiamin content to 30%, and increased urinary riboflavin content by 3-fold. Other water-soluble vitamin contents did not show significant change by fasting. To further investigate the alterations of water-soluble vitamin status by starvation, rats were starved for 3 d, and water-soluble vitamin contents in the liver, blood and urine were measured during starvation. Urinary excretion of thiamin, riboflavin, vitamin B6 metabolite 4-pyridoxic acid, nicotinamide metabolites and folate decreased during starvation, but that of vitamin B12, pantothenic acid and biotin did not. As for blood vitamin levels, only blood vitamin B1, plasma PLP and plasma folate levels decreased with starvation. All water-soluble vitamin contents in the liver decreased during starvation, whereas vitamin concentrations in the liver did not decrease. Starvation decreased only concentrations of vitamin B12 and folate in the skeletal muscle. These results suggest that water-soluble vitamins were released from the liver, and supplied to the peripheral tissues to maintain vitamin nutrition. Our human study also suggested that the effect of fasting should be taken into consideration for subjects showing low urinary thiamin and high urinary riboflavin.
Bone mineral density (BMD) reflects both genetic and lifestyle factors. The aim of this cross-sectional study was to investigate the influence of vitamin D receptor (VDR) gene polymorphism and lifestyle factors on BMD in premenopausal female workers. The subjects were 162 premenopausal female employees aged 22-44 y who worked at a large-scale integrated manufacturing facility in Japan. BMD was measured at the nondominant radius by dual energy X-ray absorptiometry. Lifestyle information was obtained by a questionnaire at the same time and genomic DNA was isolated from peripheral leukocytes. BMD was positively correlated with age, weight, and body mass index (BMI). The genotype frequencies of VDR gene polymorphism detected by TaqI analysis were 77.2, 22.8, and 0.0% for TT, Tt, and tt, respectively. Analysis of covariance with adjustment for age and BMI showed that the mean BMD was significantly lower in subjects with the Tt genotype than in those with the TT genotype. Subjects who drank alcohol also showed a significantly lower BMD if they had the Tt genotype than if they had the TT genotype. According to multiple linear regression analysis, the independent determinants of BMD were age, BMI, and VDR gene polymorphism. Our data show that BMD is negatively correlated with the Tt genotype of the VDR gene, but positively correlated with age and BMI. These findings suggest that analysis of VDR gene polymorphism may be useful for identifying individuals who are susceptible to osteoporosis so that early preventive measures can be provided.
The anti-atherogenic effects of spirulina (Spirulina platensis) were investigated in the New Zealand White (NZW) rabbit model. The animal had hypercholesterolemia induced by being fed a high cholesterol diet (HCD) containing 0.5% cholesterol for 4 wk, and then fed a HCD supplemented with 1 or 5% spirulina (SP1 or SP5) for an additional 8 wk. Spirulina supplementation lowered intimal surface of the aorta by 32.2 to 48.3%, compared to HCD. Serum triglyceride (TG) and total cholesterol (TC) significantly were reduced in SP groups. After 8 wk, serum low density lipoprotein cholesterol (LDL-C) remarkably decreased by 26.4% in SP1 and 41.2% in SP5, compared to HCD. On the other hand, high density lipoprotein cholesterol (HDL-C) was markedly increased in SP1 and SP5 compared with that in the HCD group from 2 to 8 wk. These results suggest that spirulina intake can cause the reduction of hypercholesterolemic atherosclerosis, associated with a decrease in levels of serum TC, TG and LDL-C, and an elevation of HDL-C level. Spirulina may, therefore, be beneficial in preventing atherosclerosis and reducing risk factors for cardiovascular diseases.
We evaluated the characteristics of a coenzyme Q10 (CoQ10) formulation created with gum arabic. We defined the formulation’s “modulus of inclusion,” a reference index of the emulsified state, as the CoQ10 not extracted by hexane as a percentage of the total CoQ10 content of the formulation. The emulsified CoQ10 formulation had a smaller particle size and larger modulus of inclusion value than the equivalent unemulsified formulation. In a kinetic study in rats, serum CoQ10 levels were significantly greater with the emulsified CoQ10 formulation than with the equivalent unemulsified formulation, which barely increased the levels. In a human study, oral intake of the emulsified formulation significantly increased plasma CoQ10 levels, which peaked 6 h after intake, compared with the equivalent unemulsified formulation or CoQ10 bulk powder. There was a significant positive correlation between baseline plasma CoQ10 and total cholesterol levels, but no correlation was observed between absorption of CoQ10 and baseline CoQ10 levels. The emulsified CoQ10 formulation was highly stable against heat and high humidity and in the presence of some materials (magnesium oxide, vitamin C, and vitamin E). In conclusion, emulsification of CoQ10 using gum arabic increased bioavailability in both rats and humans and improved suitability for food processing.
Pleurotus eryngii water extract (PEE), which showed the most significant inhibitory activity against pancreatic lipase in vitro among eight edible mushrooms, was investigated to determine the mechanism of its anti-lipase activity in vitro and its hypolipidemic effect in fat-loaded mice. The inhibitory effects of mushroom extracts on pancreatic lipase activity were examined using 4-methylumbelliferyl oleate (4-MUO) or trioleoylglycerol emulsified with lecithin, gum arabic or Triton X-100 as a substrate. For in vivo experiments, blood samples were taken after oral administration of corn oil and [3H]trioleoylglycerol with or without PEE to food-deprived mice. PEE inhibited hydrolysis of 4-MUO and trioleoylglycerol emulsified with lecithin or Triton X-100, but not that of trioleoylglycerol emulsified with gum arabic. PEE suppressed the elevations of plasma and chylomicron triacylglycerol levels after oral administration of corn oil, but had no effect on lipoprotein lipase activity. [3H]Trioleoylglycerol absorption was also decreased by administration of PEE. The results of in vitro studies suggest that PEE may prevent interactions between lipid emulsions and pancreatic lipase. The hypolipidemic effect of PEE in fat-loaded mice may be due to low absorption of fat caused by the inhibition of pancreatic lipase.
We examined whether two types of xylooligosaccharides (neutral or acidic xylooligosaccharides) derived from hardwood kraft pulp ameliorate the development of atopic dermatitis (AD)-like skin lesions induced by repeated application of picryl chloride (PiCl) in NC/Nga mice. Oral administration of acidic xylooligosaccharides at a daily dose of 100 mg/kg significantly prevented the development of AD-like skin lesions. Serum histamine level was significantly suppressed, but serum total IgE level was not significantly suppressed. Moreover, the secretion of inflammatory cytokine IL-12 from splenic lymphocytes was significantly suppressed. On the other hand, neutral xylooligosaccharides showed no significant preventive effect on the development of AD-like symptoms. These results suggest that oral administration of acidic xylooligosaccharides may be effective in preventing the development of AD-like skin disease and one of the mechanisms is the suppressive effect on IL-12.
We attempted to isolate the constituent(s) responsible for the suppressive effect of the juice of shekwasha, a citrus produced in Okinawa Prefecture, on D-galactosamine (GalN)-induced liver injury in rats. Liver injury-suppressive activity, as assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, was found only in the fraction that was extracted with n-hexane when three fractions were added to the diet and fed to rats. Of five compounds isolated from the n-hexane-soluble fraction by silica gel column chromatography, three compounds had liver injury-suppressive effects when five compounds were singly force-fed to rats at a level of 300 mg/kg body wt 4 h before the injection with GalN. The structures of the three active compounds were determined as 3',4',5,6,7,8-hexamethoxyflavanone (citromitin), 4',5,6,7,8-pentamethoxyflavone (tangeretin) and 3',4',5,6,7,8-hexamethoxyflavone (nobiletin), which are known flavonoids mainly existing in citrus. Nobiletin, the most important compound in the n-hexane-soluble fraction, also had suppressive effects on liver injuries induced by carbon tetrachloride, acetaminophen and GalN/lipopolysaccharide (LPS) in addition to liver injury induced GalN. Nobiletin suppressed GalN/LPS-induced increases in plasma tumor necrosis factor (TNF)-α and nitric oxide (NO) concentrations and hepatic mRNA levels for inducible NO synthase and DNA fragmentation. These results suggest that nobiletin suppressed GalN/LPS-induced liver injury at least by suppressing the production of both TNF-α and NO. The results obtained here indicate that the hepatoprotective effect of shekwasha juice is mainly ascribed to several polymethoxy flavonoids included in the juice.
This study was conducted to elucidate the effects of dietary polyphenols on intestinal immunoglobulin A (IgA) response and mucin levels in rats fed a high-fat diet. In experiment 1, rats were fed a high-fat diet with or without several polyphenols including curcumin, rutin, D(+)-catechin, ellagic acid and quercetin at the level of 0.5%. Among the polyphenols examined, consumption of curcumin markedly elevated the level of IgA in feces and colon contents. In experiment 2, rats were fed a high-fat diet or a low-fat diet with or without 0.5% curcumin. Fecal level of IgA was higher in the high-fat diet group than in the low-fat diet group. In the rats fed the high-fat diet, dietary curcumin elevated fecal IgA, but not in those fed the low-fat diet. These results imply a novel effect of curcumin on intestinal IgA in animals fed a high-fat diet.
Although an immunomodulatory role of the soy isoflavone genistein has been demonstrated, the effects of other soy isoflavones on induction of antigen (Ag)-specific immune responses are not known. In this study, we therefore investigated the effects of daidzein and equol on ovalbumin (OVA)-specific T cell and B cell responses in BALB/c mice. Mice that had been treated with 20 mg/kg equol showed a significantly higher level of OVA-specific IgE than control mice. Levels of interferon (IFN)-γ and interleukin (IL)-4 production were not different between the control and equol groups. However, IL-13 production level in mice administered 20 mg/kg equol was significantly higher than that in control mice. Strong induction of OVA-specific IgE production by equol was also observed in ovariectomized BALB/c mice, suggesting that the immunomodulatory effect of equol is not affected by endogenous estrogen.
The beneficial effect of coenzyme Q10 (CoQ10) on human health occurs through various mechanisms including the possibility of immunomodulation. Therefore, the purpose of study was to examine the in vitro effect of CoQ10 on cytokine production and superoxide anion generation by human peripheral blood mononuclear cells (PBMC). 2×106/mL PBMC obtained from 19 volunteers were incubated for 24 h without or with 0.6, 1.25, 2.5 and 5.0 μM of CoQ10. The production of the following cytokines were examined: IL-1β, IL-1ra, IL-6, IL-10, IL-2 and IFNγ. Superoxide anion production was examined by incubation of 4×106/mL cells with CoQ10 and 2×10−3 mM phorbol merystate acetate (PMA) for 60 min. The production of the proinflammatory cytokines IL-1β, IL-6 and IFNγ and that of the anti-inflammatory cytokines IL-1ra and IL-10 by PBMC was not affected by CoQ10, whereas TNFα secretion was significantly decreased when the cells were incubated with 0.6 and 1.25 μM of CoQ10. On the other hand, increasing doses of CoQ10 caused mild, but statistically significant inhibition of IL-2 secretion. The generation of superoxide anion by PBMC did not differ significantly between cells incubated with or without CoQ10 at concentrations between 0.3 and 5.0 μM. The results suggest that CoQ10 exerts a certain effect on cytokine production by PBMC related to its capacity to modulate human immune function.