Pancreatic islets are responsible for blood glucose homeostasis. Reduced numbers of functional (insulin-secreting) beta-cells in pancreatic islets underlies diabetes. Restoration of the secretion of the proper amount of insulin is a goal. Beta-cell mass is increased by neogenesis, proliferation and cell hypertrophy, and is decreased by beta-cell death primarily through apoptosis. Many hormones and nutrients affect beta-cell mass, and glucose and free fatty acid are thought to be the most important determinants of beta-cell equilibrium. A number of molecular pathways have been implicated in beta-cell mass regulation and have been studied. This review will focus on the role of the principle metabolites, glucose and free fatty acid, and the downstream signaling pathways regulating beta-cell mass by these metabolites.
Apoptosis ; Blood Glucose ; Fatty Acids, Nonesterified* ; Glucose* ; Homeostasis ; Hypertrophy ; Insulin ; Islets of Langerhans

OBJECTIVETo analyze serum levels of non-esterified fatty acids (NEFA) and albumin (ALB) in children with nephrotic syndrome (NS) and investigate the clinical significance of altered serum NEFA to ALB ratio in children with NS in acute and remission phases.

METHODSSerum levels of NEFA and ALB were measured in 55 NS children in acute phase, in 33 NS children in remission and in 122 healthy control children, and the ratio of NEFA to ALB was calculated. The other lipid/lipoprotein and renal function parameters were also analyzed in these children.

RESULTSCompared with the healthy control children, children with NS had a significantly decreased serum ALB level (t=11.152, P<0.001) and a significantly increased NEFA to ALB ratio (t=4.991, P<0.001). Compared with NS children in remission, those in acute phase showed a significantly decreased ALB (Z=7.822, P<0.001) and an increased NEFA to ALB ratio (t=4.991, P<0.001). In all the NS children, NEFA to ALB ratio was positively correlated with the levels of TC (r=0.564, P<0.001), TG (r=0.444, P<0.001), LDL-C (r=0.625, P<0.001), urea (r=0.437, P<0.001), creatinine (r=0.278, P=0.013), and uric acid (r=0.397, P<0.001), while negatively correlated with the level of total protein (r=-0.461, P<0.001). Multiple linear regression analyses showed that NEFA to ALB ratio was independently associated with serum urea levels (β=0.703, P=0.001; adjusted R=0.494) after adjustment of other related factors.

CONCLUSIONSerum NEFA to ALB ratio is significantly increased in NS children in close association with impaired kidney function, and may function as a novel parameter for assessing the development of NS.

Case-Control Studies ; Child ; Fatty Acids, Nonesterified ; blood ; Humans ; Nephrotic Syndrome ; blood ; Regression Analysis ; Serum Albumin, Human ; analysis

OBJECTIVETo explore the intervention effect of Qushi Huayu Decoction (QHD) on high-fat diet induced hepatic lipid deposition and its dose-effect relationship in rats.

METHODSFatty liver model of rats were established simply by 10 weeks of high-fat diet feeding, and starting from the 7th week of modeling, they were gastric perfused respectively with saline (model group), high-dose QHD (QHDh group), low-dose QHD (QHDI group) and polyene phosphatidylcholine (PP group) for successive 4 weeks. Liver pathology by electron microscope observation with HE staining and oil red staining; contents of triglyceride (TG) and free fatty acid (FFA) in liver tissue; and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and TG in rats were determined.

RESULTSIn the model group, the significant hepatic steatosis and vesicle changes as well as severe accumulation of middle- and micro-sized fatty drops in the hepatocyte plasma were found under electron microscope; with TG and FFA contents in liver tissue elevated to 3.2 and 3.5 multiples of those in normal group respectively, but, the difference between them in serum levels of ALT, AST, TG and TC were not significant. Above-mentioned pathological changes in the QHDh, QHDI and PP groups were all ameliorated significantly with the hepatic TG decreased to 57.55%, 72.32% and 71.07%, and FFA decreased to 48.95%, 65.67%, 55.57% of those in model group respectively, especially the effect of QHDh in reducing TG was superior to that of QHDI and PP (P < 0.05).

CONCLUSIONQHD shows an evident fatty liver antagonizing effect in rats induced by high-fat diet in a dose-dependent manner.

Animals ; Diet, High-Fat ; Drugs, Chinese Herbal ; therapeutic use ; Fatty Acids, Nonesterified ; blood ; Fatty Liver ; blood ; drug therapy ; Lipids ; blood ; Male ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; blood

Hyperglycemia is associated with an increased risk of cardiovascular diseases. It has been demonstrated that chronic exposure to high glucose impaired endothelial functions. However, specific effects of short-term exposure to high glucose on vascular reactivity are controversial. Moreover, the combined effects of other metabolic substrates such as free fatty acids (FFA) on vascular reactivity remain poorly understood. Here we investigate the effects of short-term exposure to high glucose with or without other metabolic substrates including FFAs termed “nutrition full” (NF) solution, on mesenteric (MA) and deep femoral arteries (DFA) of rats. Arterial ring segments were mounted in a double-wire myograph. Contraction in response to phenylephrine (PhE) was determined in control (5 mM) and high glucose (23 mM, HG) environments over a 30 min period. In both arteries, PhE-inducedvasocontraction was enhanced by pre-incubation of HG solution. A combined incubation with HG and palmitic acid (100 µM) induced similar sensitization of PhE-contractions in both arteries. In contrast, high K⁺-induced contractions were not affected by HG. Interestingly, pre-incubation with NF solution decreased PhE-induced contraction in MA but increased the contraction in DFA. In NF solution, the HG-induced facilitation of PhE-contraction was not observed in MA. Furthermore, the PhE-induced contraction of DFA was attenuated by HG in NF solution. Our results demonstrate that the sensitization of PhE-induced arterial contraction by HG is differentially affected by other metabolic substrates. The conversation of skeletal arterial contractility by HG in NF solution requires careful interpretation of the previous in vitro studies where only glucose is included in physiological salt solutions. Further studies are required to elucidate the mechanism underlying the inconsistent effect of NF solution on MA and DFA.
Animals ; Arteries ; Blood Vessels ; Cardiovascular Diseases ; Fatty Acids ; Fatty Acids, Nonesterified ; Femoral Artery* ; Glucose* ; Hyperglycemia ; In Vitro Techniques ; Isometric Contraction ; Palmitic Acid ; Phenylephrine ; Rats*

Investigation in our laboratory has been undertaken to study the effect of ethanol on the triglyceride (TG) content in the liver, the free fatty acid (FFA) content in the serum and the glycogen in the liver of rats which were fed on various diets. Four hours after administration of a sing1e dose of glucose (5g/kg BW.) and ethanol (6g/kg BW.) by gavage tube to rats fed a norma1 diet for 20 days then fasted for 18 hours, TG content in the liver increased by 80%, 10% compared to the control. When a sing1e dose of equal amounts of both glucose and ethanol were administered to another group, TG content in the liver was 42% higher than the control. There was no great change in serum FFA content in the glucose treated group as compared with the control, however, there was an increment of serum FFA content in the ethanol treated group and in the group treated with both ethanol and glucose by 81% and 71% of the control, respectively. The results indicate that ethanol administration had an inhibitory effect on the TG accumulation in the liver of rats fed by glucose. There is a correlation between TG accumulation in the liver and FFA content in the serum, and it appears that the ethanol administration did not induce the TG accumulation in the liver but the increment of serum FFA content in rats is probably due to the increased fatty acid mobilization from adipose tissue. However, countercurrent results were observed in the glucose treated group as compared with the ethanol treated group suggesting that glucose administration does induce TG accumulation in the liver but does not increase the serum FFA content in rats. The increment of serum FFA content in rats. The increment of serum FFA content by ethanol treatment was not ameliorated by glucose administration. In the liver perfusion experiment with rats fed both ethanol and various other diets, the results of incorporation of ethanol-1-14C into the total lipid in the high carbohydrate, high fat, low carbohydrate and control diet group were 1925 +/- 257 (cpm/g liver), 1237 +/- 76, 1269 +/- 105, 2041 +/- 74, respective1y. The results indicate that amount of dietary carbohydrate and high fat had an effect on the total lipid accumulation derived from ethanol-1-14C molecule in the liver. Liver glycogen content in the control on rats, high fat, 1ow carbohydrate and high carbohydrate diets were 91.5 +/- 7.9(mg%), 93.0 +/- 1.8, 99.1 +/- 4.4, and 153.7 +/- 26.0, respectively. There were no great differences between each dietary group and the rest control group except in the case of the high carbohydrate group which was over 1.5 times greater than that of the control. The incorporation of labelled ethanol into liver glycogen in the control rats and those on high fatdiet, low carbohydrate diet and high carbohydrate diet were 525, 401, 351 and 806 cpm/g liver, respectively. The increased incorporation of ethanol-1-14C into liver glycogen in the high carbohydrate diet group is thought to be due to the increased gluconeogenesis from acetyl CoA derived from 14C from ethanol because rats were fasted for 18 hours before perfusion. It might be the result of increased gluconegenesis of acetyl CoA derived from ethanol-1-14C by spare action of high carbohydrate on acetyl CoA. During the liver perfusion, 14CO2 production from ethanol-1-14C was higher in the high fat diet and low carbohydrate diet groups than in the control group, however, no great difference was observed between the high carbohydrate and control groups. The higher production of 14CO2 from the single ethanol-1-14C dose in rats on the high fat diet and low carbohydrate diet groups than in the control group is probably due to the increased metabolism of ethanol through Kreb's cycle rather than the incorporation of it into the liver fat.
Animal ; Diet ; Ethanol/metabolism ; Ethanol/pharmacology* ; Fatty Acids, Nonesterified/blood ; Glucose/pharmacology ; In Vitro ; Liver/metabolism* ; Male ; Rats ; Triglycerides/metabolism*

Decreased glucose tolerance is often found in patients with thyrotoxicosis but the pathogenetic mechanisms are poorly understood. Since the concentrations of free fatty acid are usually elevated due to increased lipolysis in thyrotoxicosis, the preferential oxidation of the free fatty acids may explain the decreased glucose tolerance in hyperthyroidism. The aim of this study was to investigate whether lowering plasma free fatty acid(FFA) by acipimox, a long-acting antilipolytic agent, could affect glucose metabolism in thyrotoxicosis. We performed intravenous glucose tolerance test with acipimox or placebo in 6 untreated thyrotoxicmen and 6 age-and body mass index(BMI)-matched controls. The following results were obtained.1) The basal plasma FFA concentration in thyrotoxic patients were significantly higher than those in controls(997.0+-303.4 uEq/L vs. 290.5+-169.1 uEq/L; p<0.01). 2) Plasma FFA concentrations decreased rapidly with acipimox ingestion in both controls and thyrotoxic patients.3) Plasma glucose concentrations were significantly lower with acipimox ingestion than with placebo in thyrotoxic patients from 17min after intravenous glucose load and to the end of the study.4) Plasma insulin concentrations in thyrotoxic patients with acipimox ingestion were higher at 5, 7 min after iv glucose load.5) In thyrotoxic patients, glucose disappearance rate(K_glucose) in acipimox treatment was significantly higher than that in placebo treatment(2.44+-0.84 vs. 1.58+-0.37;p<0.05). 6) K_glucose values were inversely correlated with basal FFA concentrations(r=-0.58, p<0.05). In summary, in thyrotoxic patients with elevated plasma FFA levels, acipimox lowered plasma FFA, which in turn improved glucose tolerance.
Blood Glucose ; Eating ; Fatty Acids, Nonesterified ; Glucose ; Glucose Tolerance Test ; Humans ; Hyperthyroidism ; Insulin ; Lipolysis ; Metabolism ; Plasma ; Thyrotoxicosis

OBJECTIVETo observe the efficacy of Zaozhu Yinchen Recipe (ZZYCR) on non-alcoholic steatohepatitis (NASH) patients, and to explore its effect on serum free fatty acid (FFA) and tumor necrosis factor alpha (TNF-alpha).

METHODSTotally 120 patients with NASH were randomly assigned to the treatment group (60 cases, treated with ZZYCR, one dose per day) and the control group (60 cases, treated with Silibin Meglumine Tablets, 20 mg each time, thrice per day). The therapeutic course for all was 24 weeks. Serum levels of ALT and AST activities, TC and TG levels were detected before and after treatment. Peritoneal CT was performed in all patients, and CT ratios of liver and spleen calculated. NAFLD activity score (NAS) and degree of hepatic fibrosis were assessed using pathological examinations of liver tissue, and efficacy also evaluated. Serum contents of FFA and TNF-alpha were also detected.

RESULTSCompared with before treatment in the same group, activities of ALT and AST, serum levels of TC, TG, FFA, and TNF-alpha, NAS, scores of symptoms and signs all obviously decreased, degree of hepatic fibrosis was obviously improved in the two groups (P < 0.05, P < 0.01). These changes were more obviously seen in the treatment group (P < 0.05). After 24-week treatment, the total effective rate and total clinical efficacy were 80.00% (48/60 cases) and 85.00% (51/60 cases) in the treatment group, obviously higher than those in the control group [60.00% (36/60 cases) and 73.33% (44/60 cases) respectively], with significant difference (P < 0.05, P < 0.01).

CONCLUSIONZZYCR could improve the clinical efficacy of NASH patients, and its mechanism might be associated with inhibiting serum levels of FFA and TNF-alpha.

Drugs, Chinese Herbal ; therapeutic use ; Fatty Acids, Nonesterified ; blood ; Humans ; Non-alcoholic Fatty Liver Disease ; drug therapy ; Tumor Necrosis Factor-alpha ; blood

Resistin, a newly discovered peptide hormone mainly secreted by adipose tissues, is present at high levels in serum of obese mice and may be a potential link between obesity and insulin resistance in rodents. However, some studies of rat and mouse models have associated insulin resistance and obesity with decreased resistin expression. In humans, no relationship between resistin level and insulin resistance or adiposity was observed. This suggests that additional studies are necessary to determine the specific role of resistin in the regulation of energy metabolism and adipogenesis. In the present study, we investigated the effect of resistin in vivo on glucose and lipid metabolism by over-expressing resistin in mice by intramuscular injection of a recombinant eukaryotic expression vector pcDNA3.1-Retn encoding porcine resistin gene. After injection, serum resistin and serum glucose (GLU) levels were significantly increased in the pcDNA3.1-Retn-treated mice; there was an obvious difference in total cholesterol (TC) level between the experiment and the control groups on Day 30. In pcDNA3.1-Retn-treated mice, both free fatty acid (FFA) and high density lipoprotein (HDL) cholesterol levels were markedly lower than those of control, whereas HDL cholesterol and triglyceride (TG) levels did not differ between the two groups. Furthermore, lipase activity was expressly lower on Day 20. Our data suggest that resistin over-expressed in mice might be responsible for insulin resistance and parameters related to glucose and lipid metabolism were changed accordingly.
Animals ; Blood Glucose ; analysis ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Fatty Acids, Nonesterified ; blood ; Glucose ; metabolism ; HeLa Cells ; Humans ; Lipid Metabolism ; Male ; Mice ; Resistin ; blood ; physiology ; Triglycerides ; blood

OBJECTIVETo study the hormonal and metabolic responses of fetal lamb during cardiopulmonary bypass.

METHODSSix pregnant ewes underwent fetal cardiopulmonary bypasses with artificial oxygenators and roller pumps for 30 minutes, which maintained the blood gas value at the fetal physiological level. The fetal blood pressure, heart rate, pH value and blood lactate levels were monitored. The levels of catecholamine, cortisol and insulin were measured pre-bypass and then again 30 minutes later. The blood glucose and free fatty acid levels were monitored continuously during the bypass. Fetal hepatic PAS staining was also carried out.

RESULTSThere were no changes before and during the bypass in fetal blood pressure, heart rate and blood gas. However, pH values decreased and blood lactate levels increased (P < 0.05). The fetal catecholamine and cortisol levels increased significantly (P < 0.01), while the levels of insulin did not change. The blood glucose and free fatty acid levels increased at the beginning of the bypass (P < 0.01), and then gradually slowed down during the bypass. The fetal hepatic PAS staining showed that hepatic glycogen was consumed in large amounts. After 30 minutes of bypass, the fetal lamb would not survive more than 1 hour.

CONCLUSIONThe fetal lamb has a strong negative reaction to cardiopulmonary bypass.

Animals ; Blood Gas Analysis ; Blood Glucose ; analysis ; Cardiopulmonary Bypass ; adverse effects ; Catecholamines ; blood ; Fatty Acids, Nonesterified ; blood ; Fetus ; physiology ; Hemodynamics ; physiology ; Hydrocortisone ; blood ; Lactates ; blood ; Sheep

OBJECTIVETo observe serum adiponectin, free fatty acid (FFA) profile and other glucose and lipid metabolic parameters in essential hypertensive patients with metabolic syndrome (HPMS) or without metabolic syndrome (HP).

METHODSThe serum adiponectin was measured with the radioimmunoassay, FFA profile measured with the gas chromatography and mass spectrometer in 72 HPMS, 56 HP and 43 normal control subjects.

RESULTSSerum adiponectin were significantly lower in HPMS group than those in the HP and control group (P < 0.05 or P < 0.01). Serum total free fatty acid (TFA), unsaturated fatty acid (UFA, linoleic acid, oleic acid, arachidonic acid, docosahexaenoic acid, eicosatrienoic acid), polyunsaturated fatty acid (PUFA) and n6PUFA were significantly higher in HPMS group than those in the HP and control groups (P < 0.05 or P < 0.01). Adiponectin was negatively correlated with body mass index, waist circumferences, waist hip ratio, triglycerides (r = -0.222, -0.235, -0.179, -0.194, P < 0.01 or P < 0.05, respectively) and positively correlated with high-density lipoprotein cholesterol (r = 0.336, P < 0.01); TFA and PUFA were positively correlated with body mass index, waist circumferences, fasting blood glucose, mean arterial pressure (r = 0.241 and 0.280, 0.198 and 0.188, 0.226 and 0.298, 0.274 and 0.334, P < 0.01 or P < 0.05, respectively) in all subjects.

CONCLUSIONOur data suggest that changes in serum adiponectin, FFA and n6PUFA might promote the development of metabolic syndrome in essential hypertensive patients.

Adiponectin ; blood ; Aged ; Fatty Acids, Nonesterified ; blood ; Female ; Humans ; Hypertension ; blood ; complications ; epidemiology ; Male ; Metabolic Syndrome ; blood ; complications ; epidemiology ; Middle Aged