glycogen and Hypertriglyceridemia

The inedible bottom part of asparagus (Asparagus officinalis L.) spears, around one-third to one-half of the total length, is always discarded as by-product. Since it still contains various bioactive substances, this by-product might have potential usage in food supplements for its therapeutic effects. In this study the hypoglycaemic effect of the aqueous extract of asparagus by-product (AEA) was evaluated in a streptozotocin (STZ)-induced diabetic rat model.. Continuous administration of AEA for 21 days significantly decreased fasting serum glucose and triglyceride levels but markedly increased body weight and hepatic glycogen level in diabetic rats. In an oral glucose tolerance test, both the blood glucose level measured at 30, 60 and 120 min after glucose loading and the area under the glucose curve showed a significant decrease after AEA treatment.. The results of this study demonstrate that AEA has hypoglycaemic and hypotriglyceridaemic functions, suggesting that it might be useful in preventing diabetic complications associated with hyperglycaemia and hyperlipidaemia.

Topics: Animals; Asparagus Plant; Diabetes Mellitus, Type 1; Dietary Supplements; Food-Processing Industry; Glucose Intolerance; Glycogen; Hypertriglyceridemia; Hypoglycemia; Hypoglycemic Agents; Industrial Waste; Liver; Male; Plant Extracts; Plant Stems; Random Allocation; Rats; Rats, Sprague-Dawley; Streptozocin; Weight Loss

Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance with the molecular basis of this association being not well understood. Here we studied the effect of hepatic triglyceride accumulation induced by postprandial triglyceride-rich lipoproteins (TGRL) on hepatic insulin sensitivity in HepG2 cells. Incubation of HepG2 cells with purified TGRL particles induced hepatocellular triglyceride accumulation paralleled by diminished insulin-stimulated glycogen content and glycogen synthase activity. Accordingly, insulin-induced inhibition of glycogen synthase phosphorylation as well as insulin-induced GSK-3 and AKT phosphorylation were reduced by TGRL. The effects of TGRL were dependent on the presence of apolipoproteins and more pronounced for denser TGRL. Moreover, TGRL effects required the presence of heparan sulfate-proteoglycans on the cell membrane and lipase activity but were independent of the cellular uptake of TGRL particles by receptors of the LDL receptor family. We suggest postprandial lipemia to be an important factor in the pathogenesis of NAFLD.

Topics: Adult; Fatty Liver; Glycogen; Glycogen Synthase; Glycogen Synthase Kinase 3; Hep G2 Cells; Humans; Hypertriglyceridemia; Insulin Resistance; Lipoproteins; Liver; Male; Non-alcoholic Fatty Liver Disease; Postprandial Period; Proto-Oncogene Proteins c-akt; Receptors, LDL; Triglycerides

Acute exercise, undertaken on the day before an oral fat tolerance test (OFTT), typically reduces postprandial triglycerides (TG) and increases high-density lipoprotein-cholesterol (HDL-C). However, the benefits of acute exercise may be overstated when studies do not account for compensatory changes in dietary intake. The objective of this study was to determine the influence of acute exercise, with and without carbohydrate (CHO) replacement, on postprandial lipid metabolism. Eight recreationally active young men underwent an OFTT on the morning after three experimental conditions: no exercise [control (Con)], prolonged exercise without CHO replacement (Ex-Def) and prolonged exercise with CHO replacement to restore CHO and energy balance (Ex-Bal). The exercise session in Ex-Def and Ex-Bal consisted of 90 min cycle ergometry at 70% peak oxygen uptake (Vo(2peak)) followed by 10 maximal 1-min sprints. CHO replacement was achieved using glucose solutions consumed at 0, 2, and 4 h postexercise. Muscle glycogen was 40 +/- 4% (P < 0.05) and 94 +/- 3% (P = 0.24) of Con values on the morning of the Ex-Def and Ex-Bal OFTT, respectively. Postprandial TG were 40 +/- 14% lower and postprandial HDL-C, free fatty acids, and 3-hydroxybutyrate were higher in Ex-Def compared with Con (P < 0.05). Most importantly, these exercise effects were not evident in Ex-Bal. Postprandial insulin and glucose and the homeostatic model assessment of insulin resistance (HOMA(IR)) were not significantly different across trials. There was no relation between the changes in postprandial TG and muscle glycogen across trials. In conclusion, the influence of acute exhaustive exercise on postprandial lipid metabolism is largely dependent on the associated CHO and energy deficit.

Topics: Administration, Oral; Dietary Carbohydrates; Energy Metabolism; Exercise; Exercise Test; Food Deprivation; Glucose Tolerance Test; Glycogen; Hemodynamics; Humans; Hypertriglyceridemia; Insulin; Insulin Resistance; Male; Muscle, Skeletal; Oxygen Consumption; Postprandial Period; Pulmonary Gas Exchange; Triglycerides

Elevated blood triacylglycerol (TG) is a significant contributing factor to the current epidemic of obesity-related health disorders, including type-2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. The observation that mice lacking the enzyme sn-glycerol-3-phosphate acyltransferase are protected from insulin resistance suggests the possibility that the regulation of TG synthesis be a target for therapy. Five-week-old Zucker Diabetic Fatty (ZDF) rats were fed a diet containing (R)-alpha-lipoic acid (LA, approximately 200mg/kg body weight per day) for 5 weeks. LA offset the rise in blood and liver TG by inhibiting liver lipogenic gene expression (e.g. sn-glycerol-3-phosphate acyltransferase-1 and diacylglycerol O-acyltransferase-2), lowering hepatic TG secretion, and stimulating clearance of TG-rich lipoproteins. LA-induced TG lowering was not due to the anorectic properties of LA, as pair-fed rats developed hypertriglyceridemia. Livers from LA-treated rats exhibited elevated glycogen content, suggesting dietary carbohydrates were stored as glycogen rather than becoming lipogenic substrate. Although AMP-activated protein kinase (AMPK) reportedly mediates the metabolic effects of LA in rodents, no change in AMPK activity was observed, suggesting LA acted independently of this kinase. The hepatic expression of peroxisome proliferator activated receptor alpha (PPARalpha) target genes involved in fatty acid beta-oxidation was either unchanged or decreased with LA, indicating a different mode of action than for fibrate drugs. Given its strong safety record, LA may have potential clinical applications for the treatment or prevention of hypertriglyceridemia and diabetic dyslipidemia.

Topics: AMP-Activated Protein Kinases; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Energy Intake; Fatty Acids; Glycogen; Hypertriglyceridemia; Lipoproteins, VLDL; Liver; Male; Oxidation-Reduction; PPAR alpha; Rats; Rats, Zucker; Thioctic Acid; Triglycerides

The effect of coconut fat (rich in medium saturated fatty acids) or fish oil (rich in omega-3 polyunsaturated fatty acids) supplementation for 2 generations on tumor growth, cancer cachexia, animal survival and macrophage function was investigated in Walker 256 tumor-bearing rats. Female Wistar rats were supplemented with coconut fat or fish oil prior to mating and then throughout pregnancy and gestation. Both supplementations were daily and orally given at 1 g per kg body weight as a single bolus. Same treatment was performed by the 2 following generations. At 90 days of age, male offspring (50%) from F2 generation were subcutaneously inoculated with 2 x 10(7) Walker 256 tumor cells. At 14 days after tumor implantation, rats not supplemented displayed cancer cachexia characterized by loss of body weight, hypoglycemia, hyperlacticidemia, hypertriglyceridemia, decreased food intake and depletion of glycogen stores in the liver and skeletal muscles. Supplementation with coconut fat did not affect these parameters. However, supplementation with fish oil decreased tumor growth (59%), prevented body weight loss and food intake reduction and attenuated cancer cachexia. In addition, fish oil increased animal survival up to 20 days (from 25% in rats not supplemented to 67% in rats supplemented with fish oil) and improved macrophage function characterized by increased phagocytosis capacity and production of hydrogen peroxide and nitric oxide. These results suggest that fish oil supplementation for 2 generations improves macrophage function in association to reduced tumor growth and attenuated cancer cachexia, maintaining food intake and increasing animal survival.

Topics: Animals; Blood Glucose; Body Weight; Cachexia; Carcinoma 256, Walker; Coconut Oil; Eating; Fatty Acids, Omega-3; Female; Fish Oils; Glycogen; Hypertriglyceridemia; Hypoglycemia; Lactic Acid; Liver Glycogen; Macrophages, Peritoneal; Muscle, Skeletal; Phagocytosis; Plant Oils; Rats; Rats, Wistar

The aim of the study was to determine the contribution of skeletal muscle, adipose tissue and liver to the impaired glucose clearance manifesting itself during the initial phase of OGTT in a non-obese animal model of insulin resistance, hereditary hypertriglyceridemic (HHTg) rats. Glucose utilisation and storage in insulin target tissues in vivo and in vitro after a glucose load (3 g/kg b. wt.) administered intragastrically following overnight fasting was compared in adult male HHTg rats and Wistar normotriglyceridemic controls after short-term (2 wk) high-sucrose (70 % calories as sucrose) feeding period. In comparison with normotriglyceridemic controls, in HHTg rats the glucose administration did not stimulate GLUT4 translocation to the plasma membrane in skeletal muscle and adipose tissue that was associated with decreased glucose utilisation by these tissues in vitro. The acute glucose supply did not result in increased glycogen synthesis in the liver and fatty acid synthesis de novo in adipose tissue. On the contrary, the serum glucose, triglyceride and free fatty acid levels remained elevated. In conclusion, in the tissues of HHTg rats, despite the increased insulinemia, the processes leading toward increased glucose utilisation and processes transforming glucose into storage forms, such as triglycerides in adipose tissue and glycogen in skeletal muscle and liver, did not start within this time interval. The combination of the impaired glucose utilisation and the impaired glucose storage in energy reserves leads to higher glycaemia following glucose load in HHTg rats.

Topics: Adipose Tissue; Animals; Blood Glucose; Energy Metabolism; Glucose; Glycogen; Glycogen Synthase; Hypertriglyceridemia; Lipid Metabolism; Male; Rats; Rats, Wistar; Triglycerides

In addition to their hypotensive action, angiotensin-converting enzyme (ACE) inhibitors exert a beneficial effect on glucoregulation. In the present study, the effect of ACE inhibition by captopril on glucose utilization in peripheral tissues was investigated in non-obese rats with hereditary hypertriglyceridemia (HHTg) associated with hyperinsulinemia and insulin resistance. Normotriglyceridemic Wistar rats served as controls (C). Rats of both groups received a high-sucrose diet, and a half of each group also captopril in drinking water (10 mg/kg body weight [bw]) for 2 weeks. Captopril administration reduced fasting glycemia and postprandial triglyceridemia in HHTg rats, while the fasting levels of nonesterified fatty acids (NEFA), glycerol, and lactate were decreased in both groups. The sensitivity of skeletal muscle to insulin action evaluated as in vitro 14C-glucose incorporation into glycogen was significantly increased by captopril treatment both in HHTg (3.51 +/- 0.48 v 2.0 +/- 0.12 micromol glucose/g wet weight [ww]) and C (3.32 +/- 0.21 v 2.48 +/- 0.09 micromol glucose/g ww). In isolated adipose tissue, the insulin-stimulated 14C-glucose incorporation into neutral lipids was increased, after captopril administration, by 137% in C and by 35% only in HHTg. After captopril treatment, insulin-stimulated de novo fatty acid synthesis rose significantly in C while remaining low in HHTg. The increase in esterification was comparable in both groups. Separate experiments were designed to assess the possible involvement of bradykinin in mediating captopril action. Both C and HHTg rats fed a high-sucrose diet for 2 weeks were treated with captopril (50 mg/kg orally) for 1 hour; half of each group received the specific inhibitor of bradykinin receptor HOE-140 (100 microg/kg intraperitoneally [i.p.]) 1 hour before captopril administration. In C, captopril administration enhanced the insulin-stimulated in vitro glucose incorporation into lipids in adipose tissue by 255%, and into glycogen in the musculus soleus by 45%; this effect was eliminated by HOE-140. In HHTg, neither a single dose of captopril nor HOE-140 had any effect. We conclude that long-term captopril administration increased the insulin sensitivity of peripheral tissue in both C and HHTg rats, but with different efficacy. While the insulin-sensitizing action of captopril on skeletal muscle was comparable in HHTg and C rats, there were differences in the effect of captopril on adipose tissue. The

Topics: Acylation; Adipose Tissue; Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Captopril; Esters; Fatty Acids; Fatty Acids, Nonesterified; Glucose; Glycerol; Glycogen; Hypertriglyceridemia; Hypoglycemic Agents; Insulin; Lactic Acid; Lipids; Male; Muscle, Skeletal; Postprandial Period; Rats; Rats, Wistar; Triglycerides

A considerable amount of clinical and experimental evidence now exists suggesting the involvement of free radical-mediated oxidative processes in the pathogenesis of diabetic complications. If the diabetic state is associated with a generalized increase in oxidative stress, it might well be reflected in the alterations in embryonic and fetal development during pregnancy. In the present study, incidence of the malformed fetuses, biochemical parameters and antioxidant system activity of streptozotocin (STZ)-induced diabetic pregnant rats was investigated and the results obtained were compared with those of the control group (non-diabetic). Virgin female Wistar rats were injected with 40 mg/kg streptozotocin (STZ) before mating. All the females were killed on Day 21 of pregnancy and the fetuses were analyzed. A maternal blood sample was collected by venous puncture and the maternal liver was removed for biochemical measurement. The diabetic dams presented hyperglycemia, hyperlipemia, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased reduced glutathione (GSH), hepatic glycogen and superoxide dismutase (SOD) determinations. There was an increased incidence of skeletal and visceral malformation in fetuses from diabetic rats. Our findings suggest that oxidative stress occurs in the diabetic pregnant state, which might promote maternal homeostasis alterations. These diabetic complications might be a contributory factor to conceptus damage causing embryonic death (abortion/miscarriage) or the appearance of malformations in the fetuses of diabetic dams. Antioxidant treatment of women with diabetes may be important in future attempts to prevent congenital malformations.

Topics: Animals; Antioxidants; Congenital Abnormalities; Diabetes Mellitus, Experimental; Female; Gestational Age; Glutathione; Glycogen; Hypercholesterolemia; Hyperglycemia; Hyperlipidemias; Hypertriglyceridemia; Liver; Male; Oxidative Stress; Pregnancy; Pregnancy in Diabetics; Rats; Rats, Wistar; Superoxide Dismutase; Uric Acid

In our previous study, we found that myricetin, a naturally occurring bioflavonoid, was able to stimulate glucose transport in rat adipocytes and enhance insulin-stimulated lipogenesis. We report here that after 2 days of treatment with myricetin (3 mg/12 h), hyperglycemia in diabetic rats was reduced by 50% and the hypertriglyceridemia that is often associated with diabetes was normalised. Treatment with myricetin increased hepatic glycogen and glucose-6-phosphate content. It increased hepatic glycogen synthase I activity without having any effect on total glycogen synthase nor phosphorylase a activity. It lowered phosphorylase a activity in the muscle. Thus, the hypoglycemic effect of myricetin is likely to be due to its effect on glycogen metabolism. There was no indication of serious hepatotoxicity with myricetin treatment and therefore, myricetin could be of therapeutic potential in diabetes.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Eating; Flavonoids; Glucose-6-Phosphate; Glycogen; Glycogen Synthase; Hindlimb; Hyperglycemia; Hypertriglyceridemia; Hypoglycemic Agents; Liver; Liver Glycogen; Male; Muscle, Skeletal; Phosphorylase a; Rats; Rats, Wistar