OBJECTIVETo explore the impact of 5-fluorouracil (5-FU) on glucose metabolism and pancreatic pathology.

METHODSTwenty Wistar rats were divided into 5-FU group(n=10, chemotherapy was administered intraperitoneally to animals at a dose of 20 mg/kg daily for continuous 5 days) and control group (n=10, sodium chloride was administered intraperitoneally to animals with the same dose at the same time ). Glucose tolerance was evaluated 2 and 7 days following 5-FU treatment by serial measurement of blood glucose before and after an oral glucose load. Plasma insulin concentration was determined by radioimmunoassay. Pancreatic pathology was examined with morphological method and the ultrastructural changes of β cells were observed by transmission electron microscope.

RESULTSFasting blood glucose level was significantly higher in the 5-FU group than that in the control group [(7.6±0.9) mmol/L vs. (4.6±0.6) mmol/L at day 2; (8.9±1.0) mmol/L vs. (4.7±0.6) mmol/L at day 7, P<0.01]. Insulin releasing test indicated that the early phase insulin response to glucose load was significantly diminished in animals treated with 5-FU at day 2. Insulin level was significantly lower in the 5-FU group than that in the control group at 30 min (P<0.01). The peak secretion time of plasma insulin in 5-FU group was at 60 min, similar to the control group; and plasma insulin level decreased more slowly. Plasma insulin level was higher in 5-FU groups than in control groups on 120 min and 180 min. At day 7, Insulin level was lower in the 5-FU group than that in the control group on 60 min, and the peak secretion time of plasma insulin was delayed to 120 min. Plasma insulin level was significantly increased in 5-FU group than that in control group on 180 min(P<0.01). No gross histopathological damage to the pancreas was observed at day 2 and 7 following administration of 5-FU. The structural changes of mitochondria were mainly the quantities of secretory granule diminished at day 7 under transmission electron microscope. Dilated rough endoplasmic reticula, swollen mitochondria, and the presence of adipose drops in lysosomes were found in few cells.

CONCLUSIONS5-FU-induced hyperglycemia appears to be mediated in part by a relatively deficient insulin secretion to glucose stimulation. A relative deficiency in insulin secretion following 5-FU treatment appears to be related to β cells function impairs with islet cell ultrastructural changes induced by 5-FU.

Animals ; Blood Glucose ; drug effects ; metabolism ; Female ; Fluorouracil ; pharmacology ; Insulin ; blood ; Male ; Pancreas ; drug effects ; pathology ; Rats ; Rats, Wistar

BACKGROUND: Recent research has reported that high sugar diets increase insulin resistance, without abdominal obesity, in male, but not female Wister rats. Whether a high sucrose (SU) diet increased insulin resistance in ovariectomized (OVX) rats was determined. METHODS: Female Sprague Dawley rats, weighing 273 +/- 20 g, had either an ovariectomy or a sham operation (sham). OVX and sham rats were divided into two groups: one group had a 68 En% SU diet and the other a 68 En% starch (ST) diet for 8 weeks. RESULTS: The body weight was higher in the OVX than the sham rats, regardless of dietary carbohydrate subtype. The fasting serum glucose levels did not differ according to diet and ovariectomy. However, the fasting serum insulin levels were higher in the OVX than the sham rats, and in the OVX rats, a high SU diet increased the serum insulin levels more than a high ST diet. The whole body glucose disposal rates, which referred to the state of insulin sensitivity, were lower in the OVX rats fed both the high SU and ST diets, compared to sham rats. Glycogen deposits in the soleus and quadriceps muscles were lower in the OVX rats fed high SU and ST diets than in sham rats. The glucose transporter 4 content and fraction velocity of glycogen synthase in muscles showed similar glucose disposal rates. However, the triacylglycerol content in the muscles were higher in the OVX rats with a high SU diet than those with a high ST diet. CONCLUSION: These results suggested that an OVX increased the weight gain due to higher food intakes, regardless of dietary carbohydrate subtypes. OVX-induced obesity may be involved in the induction of insulin resistance from an increased triacylglycerol content, decreased glucose uptake and glycogen synthesis in skeletal muscles, regardless of dietary carbohydrate subtypes.
Animals ; Blood Glucose/*drug effects/*metabolism ; Body Weight/drug effects ; Dietary Carbohydrates/*administration & dosage ; Energy Intake/drug effects ; Estradiol/blood ; Female ; Glucose Clamp Technique ; Glucose Transporter Type 4/drug effects/metabolism ; Glycogen/metabolism ; Glycogen Synthase/drug effects/metabolism ; Insulin/blood ; *Insulin Resistance ; Leptin/blood ; Models, Animal ; Muscle, Skeletal/metabolism ; *Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Triglycerides/metabolism

OBJECTIVETo evaluate the long-term clinical effect of Tangyiping Granules (, TYP) on patients with impaired glucose tolerance (IGT) to achieve normal glucose tolerance (NGT) and hence preventing them from conversion to diabetes mellitus (DM).

METHODSIn total, 127 participants with IGT were randomly assigned to the control (63 cases, 3 lost to follow-up) and treatment groups (64 cases, 4 lost to follow-up) according to the random number table. The control group received lifestyle intervention alone, while the patients in the treatment group took orally 10 g of TYP twice daily in addition to lifestyle intervention for 12 weeks. The rates of patients achieving NGT or experiencing conversion to DM as main outcome measure were observed at 3, 12, and 24 months after TYP treatment. The secondary outcome measures included fasting plasma glucose (FPG), 2-h postprandial plasma glucose (2hPG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), 2-h insulin (2hINS), homeostatic model assessment of insulin resistance (HOMA-IR), blood lipid and patients' complains of Chinese medicine (CM) symptoms before and after treatment.

RESULTSA higher proportion of the treatment group achieved NGT compared with the control group after 3-, 12- and 24-month follow-up (75.00% vs. 43.33%, 58.33% vs. 35.00%, 46.67% vs. 26.67%, respectively, P<0.05). The IGT to DM conversion rate of the treatment group was significantly lower than that of the control group at the end of 24-month follow-up (16.67% vs. 31.67%, P<0.05). Before treatment, FPG, 2hPG, HbA1c, FINS, 2hINS, HOMA-IR, triglyceride (TG), total cholesterol, low- and high-density lipoprotein cholesterol levels had no statistical difference between the two groups (P>0.05). After treatment, the 2hPG, HbA1c, HOMA-IR, and TG levels of the treatment group decreased significantly compared with those of the control group (P<0.05). CM symptoms such as exhaustion, irritability, chest tightness and breathless, spontaneous sweating, constipation, and dark thick and greasy tongue were significantly improved in the treatment group as compared with the control group (P<0.05). No severe adverse events occurred.

CONCLUSIONTYP administered at the IGT stage with a disciplined lifestyle delayed IGT developing into type 2 DM.

Blood Glucose ; metabolism ; Blood Platelets ; drug effects ; metabolism ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Erythrocytes ; drug effects ; metabolism ; Female ; Glucose Intolerance ; blood ; drug therapy ; Humans ; Insulin ; blood ; Kidney ; drug effects ; physiopathology ; Leukocytes ; drug effects ; metabolism ; Lipids ; blood ; Liver ; drug effects ; physiopathology ; Male ; Middle Aged ; Time Factors

OBJECTIVETo examine the effects of chlorogenic acid (CGA) on lipid and glucose metabolism under a high dietary fat burden and to explore the possible role of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) in these effects.

METHODSTwenty male golden hamsters were randomly divided into CGA treatment group (n=10, given peritoneal injection of CGA solution prepared with PBS, 80 mg CGA/kg body weight daily), and control group (n=10, given PBS i.p. at the average volume of the treatment group). Animals in both groups were given 15% high fat diet. Eight weeks after treatment with CGA, the level of biochemical parameters in fasting serum and tissues and the expression of hepatic mRNA and protein PPAR-alpha were determined.

RESULTSEight weeks after treatment with CGA, the levels of fasting serum triglyceride (TG), free fatty acid (FFA), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), glucose (FSG), and insulin (FSI) were significantly lower in the GGA treatment group than in the control group. CGA also led to higher activity of hepatic lipase (HL), lower contents of TG and FFA in liver, and lower activity of lipoprotein lipase (LPL) in skeletal muscle. Furthermore, CGA significantly elevated significantly elevated the expression level of mRNA and protein expression in hepatic PPAR-alpha.

CONCLUSIONCGA can modify lipids and glucose metabolism, which may be attributed to PPAR-alpha facilitated lipid clearance in liver and improved insulin sensitivity.

Animals ; Blood Glucose ; drug effects ; Chlorogenic Acid ; pharmacology ; Cricetinae ; Dietary Fats ; pharmacology ; Gene Expression Regulation ; drug effects ; Glucose ; metabolism ; Hypolipidemic Agents ; pharmacology ; Lipase ; metabolism ; Lipid Metabolism ; drug effects ; Male ; Mesocricetus ; PPAR alpha ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Weight Gain

OBJECTIVETo observe the effect of L-arginine on diabetic rats.

METHODSForty adult male Lewis rats were randomized equally into diabetic and normal control groups, and the former rats were treated intraperitoneally with streptozotocin to induce diabetes mellitus. Seven days later, half of the diabetic and normal rats were injected intraperitoneally with L-arginine at the daily dose of 1 g/kg, while the remainder were given saline instead. All the rats were euthanized on 10 days after L-arginine or saline treatment, and their body weight, plasma protein, arginine and sugar, food and water intake were analyzed.

RESULTSDiabetic rats had obviously decreased body weight, plasma protein and arginine but increased blood sugar and food and water intakes in comparison with the control rats. L-arginine significantly increased plasma protein and arginine, decreased food and water intakes, but failed to prevent weight loss and blood sugar increment in diabetic rats as compared to their saline-treated counterparts. L-arginine supplementation did not result in any changes other than arginine elevation in the control rats.

CONCLUSIONL-arginine supplementation can partially improve polydipsia and polyphagia and increase plasma protein in diabetic rats.

Animals ; Arginine ; administration & dosage ; blood ; therapeutic use ; Blood Glucose ; metabolism ; Blood Proteins ; metabolism ; Body Weight ; drug effects ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; physiopathology ; Drinking ; drug effects ; Eating ; drug effects ; Injections, Intraperitoneal ; Male ; Rats ; Rats, Inbred Lew

Lyophilization of human red blood cells has important significance in clinical application. Some sugars, especially trehalose, can be more tolerant of some organism or cells to dry environments, But, how to bring sugars into cells is a challenge. This study was aimed to investigate the regularity of sugar-uptake in human red blood cells. The absorption rate of trehalose and glucose in red blood cells, free hemoglobin level and erythrocyte deformation index were determined at different incubation temperature (4, 25 and 37 degrees C), different sugar concentration (0, 0.2, 0.4, 0.6, 0.8 and 1 mol/L) and different incubation time (1, 3, 5, 7 and 9 hours). The results showed that with increase of temperature and extracellular sugar concentration, the uptake of sugar in red blood cells also increased, the intracellular trehalose and glucose concentrations were over 30 mmol/L and 40 mmol/L respectively. The effects of incubation time on uptake of trehalose and glucose were different. With prolonging of incubation time, the uptake of trehalose showed firstly increase and then decrease, however, the uptake of glucose showed a constant increase. But the loading process had side-effect on free hemoglobin and maximum deformation index (MAXDI) of red blood cells, especially for trehalose, which mainly come from high osmotic pressure. It is concluded that the uptake of sugars in red blood cells is closely dependent on incubation temperature, extracellular sugar concentration and incubation time. In certain condition, the efficiency of sugar uptake is very high, but this process also damages red blood cells so as to affect the application of sugars in lyophilization of red blood cells. The research in the future should focus on how to deal with the relation between cell injury and uptake efficiency of sugar in red blood cells.
Blood Preservation ; adverse effects ; Cryoprotective Agents ; pharmacokinetics ; Erythrocyte Membrane ; drug effects ; Erythrocytes ; metabolism ; Freeze Drying ; Glucose ; pharmacokinetics ; Humans ; Trehalose ; pharmacokinetics

To study insulino-mimetic effects of bis(alpha-furancarboxylato) oxovanadium (IV) (BFOV), a orally active antidiabetic vanadyl complex, on glucose uptake and lipogenesis in isolated rat adipocytes were determined by using 2-deoxy-D-[3H]-glucose and D-[3H]-glucose, respectively. Lipolysis was assayed by free fatty acids (FFA) released from isolated rat adipocytes treated with epinephrine. The results showed that BFOV, similar to insulin, concentration-dependently significantly enhanced the uptake of 2-deoxy-D-[3H]-glucose and the transformation from D-[3H]-glucose to lipid in isolated rat adipocytes, with the EC50 values of (0.31 +/- 0.08) mmol L(-1) and (0.49 +/- 0.12) mmol L(-1), respectively. Moreover, BFOV markedly inhibited FFA release from isolated rat adipocytes treated with epinephrine, and the IC50 value was (0.30 +/- 0.20) mmol L(-1). BFOV had insulino-mimetic effects such as enhancing glucose uptake and lipogenesis, as well as inhibiting lipolysis.
Adipocytes ; drug effects ; metabolism ; Animals ; Blood Glucose ; drug effects ; Hypoglycemic Agents ; pharmacology ; Insulin ; pharmacology ; Lipogenesis ; drug effects ; Male ; Organometallic Compounds ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of Huanglian Jiedu Decoction (HLJDD) on glucose transporter 4 (GLUT4) protein expressions in insulin-resistant murine target tissues.

METHODSThe experimental male Wistar rats were established into insulin resistant models by injecting streptozotocin (STZ 30 mg/kg) via caudal vein and feeding them with high fat high caloric diet, and randomly divided into the model group, the aspirin group and the HLJDD group. Besides, a normal group was set up for control. Changes of body weight (BW), levels of serum fasting blood glucose (FBG), serum fasting insulin (FINS) and oral glucose tolerance test (OGTT) were routinely determined. The expression of GLUT4 protein in adipose and skeletal muscle tissues before and after insulin stimulation was determined with Western blot.

RESULTSIn the HLJDD group after treatment, BW and FBG got decreased, OGTT improved, and the expression and translocation of GLUT4 protein elevated obviously, either before or after insulin stimulation, as compared with those in the model group, showing significant differences respectively.

CONCLUSIONThe mechanism of improving insulin resistance by HLJDD is probably associated with its effect in elevating GLUT4 protein expression and translocation in adipose and skeletal muscle tissues of insulin resistant rats.

Adipose Tissue ; drug effects ; metabolism ; Animals ; Blood Glucose ; metabolism ; Body Weight ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Fasting ; blood ; Glucose Tolerance Test ; Glucose Transporter Type 4 ; drug effects ; metabolism ; Insulin ; blood ; Insulin Resistance ; physiology ; Male ; Muscle, Skeletal ; drug effects ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo study the effects of Bushen Huatan Compound (BHC) on the glycolipid metabolism and the expressions of the insulin signal conducting molecules inside ovaries in polycystic ovary syndrome (PCOS) model rats.

METHODSFemale Wistar rats were subcutaneously injected with 2.5 mg/kg testosterone propionate (Their female offspring were randomly divided into the medication group and the model group, 10 in each.) or neutral tea oil of the same dose (Ten female offspring was taken as the control group.) on the 16th day of pregnancy, once daily, for 3 successive days. BHC was given to rats in the medication group by gastrogavage, while equal volume of distilled water was given to rats in the model group and the control group by gastrogavage, both once daily for 20 successive days. The body weight and ovary weight were weighed to calculate the ratio of wet fat weight/body weight. The blood glucose levels were detected at 0, 0.5, 1, and 2 h using oral glucose tolerance test (OGTT). The serum concentrations of high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), fasting blood glucose (FBG), and insulin were detected to calculate homeostasis model assessment of insulin resistance (HOMA-IR). The expressions of protein kinase B (AKT2), glycogen synthase kinase-3beta (GSK3beta), glucose transporter-4 (GLUT4), extracellular signal regulated kinase-1 (ERK1) protein, P-AKT2, P-GSK3beta, and P-ERK1 in ovaries were detected using Western blot.

RESULTSCompared with the control group, the ratio of wet fat weight/ body weight, the blood glucose levels at 0.5 and 2 h in OGTT, and HOMA-IR all obviously increased, and the HDL-C level obviously decreased in the model group (P < 0.05). Compared with the model group, the ratio of wet fat weight/body weight and the blood glucose levels at 2 h in OGTT obviously decreased, and the HDL-C level obviously increased in the medication group (P < 0.05). The expressions of AKT2, P-AKT2, GSK3beta, P-GSK3beta, GLUT4, and ERK1 in the ovary tissue were obviously lower in the model group than in the control group (P < 0.05). The expressions of GSK3beta, P-GSK3beta, and GLUT4 were more obviously enhanced in the medication group than in the model group (P < 0.05).

CONCLUSIONSInsulin resistance and glucolipid metabolism dysfunction existed in female PCOS rats. Besides, abnormal insulin signaling pathway existed in the ovary tissue. BHC could remarkably ameliorate the IR degree and glucolipid metabolism functions, and might be correlated with regulating the protein expressions of insulin signal conducting molecules.

Animals ; Blood Glucose ; metabolism ; Cholesterol, HDL ; blood ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Female ; Homeostasis ; Insulin ; blood ; metabolism ; Insulin Resistance ; Male ; Ovary ; drug effects ; metabolism ; Polycystic Ovary Syndrome ; metabolism ; Pregnancy ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects ; Triglycerides ; blood

OBJECTIVETo investigate the effects of Chang-Chul-Eui-Ee-In-Tang ([see text], CCEET), modififi ed CCEET (MCCEET), and Semen Coicis (SC, a major component of CCEET) on energy and glucose homeostasis. The possible mechanism of action of CCEET was also determined.

METHODSA total of 100 Sprague Dawley female rats were randomly assigned to 5 groups, with 20 in each group. Rats in 4 groups were fed with a high fat diet supplementation (2 g/kg body weight), and water extracts of CCEET, MCCEET, SC, and cellulose (negative control), respectively. The last group was fed with a low-fat diet as a positive control.

RESULTSCCEET and MCCEET decreased body weight and body fat (mesenteric and retroperitoneal fat) more than SC. This decrease was due to decreased energy intake and increased energy expenditure and fat oxidation. The improvement in energy homeostasis was associated with the enhancement of the hypothalamic leptin signalling pathway involving potentiating the phosphorylation of the signal transducer and activator of transcription-3, as well as attenuating the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK). Both CCEET and MCCEET improved glucose tolerance without changing serum insulin levels during an oral glucose tolerance test but MCCEET had a better effect than CCEET.

CONCLUSIONSBoth CCEET and MCCEET safely exerted anti-obesity effects by enhancing energy balance in female rats with diet-induced obesity; MCCEET showed a better effect on glucose homeostasis.

Adenylate Kinase ; metabolism ; Adipose Tissue ; drug effects ; Animals ; Anti-Obesity Agents ; adverse effects ; pharmacology ; therapeutic use ; Blood Glucose ; metabolism ; Body Weight ; drug effects ; Calorimetry ; Diet ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Energy Metabolism ; drug effects ; Female ; Glucose Tolerance Test ; Homeostasis ; drug effects ; Hypothalamus ; drug effects ; enzymology ; Leptin ; metabolism ; Motor Activity ; drug effects ; Obesity ; blood ; drug therapy ; pathology ; physiopathology ; Phosphorylation ; drug effects ; Rats ; Rats, Sprague-Dawley ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; drug effects