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Obesity is associated with an enhanced inflammatory response that exacerbates insulin resistance and contributes to diabetes, atherosclerosis, and cardiovascular disease. One mechanism accounting for the increased inflammation associated with obesity [...]

Cellular effects of FFA might differ from those of lipoprotein triglyceride (TG)-derived fatty acids (TGFA). The aim of the current study was to examine the relationship between lipoprotein lipase (LPL) expression, TGFA, or FFA availability and glucose metabolism in the absence of insulin in [C.sub.2][C.sub.12] myoblasts. Control myoblasts or myoblasts stably transfected with human lipoprotein lipase ([C.sub.2]/LPL; 15-fold greater LPL activity) were incubated for 12 h in fetal bovine serum-free medium in the absence or presence of Intralipid-20. Intracellular retention of labeled medium glucose was assessed in a subset of experiments. In the presence of Intralipid, medium glucose disappearance was increased in [C.sub.2]/LPL cells but not in control cells. In both cell types, glucose label retention in cellular TG was increased in the presence of Intralipid; incubation with albumin-bound oleate produced similar results. In the presence of Intralipid, the LPL hydrolytic inhibitor tetrahydrolipstatin blocked excess glucose retention in cellular TG but did not significantly decrease glucose disappearance in [C.sub.2]/LPL cells. Changes in glucose transport or hexokinase II did not explain the altered glucose disappearance in [C.sub.2]/LPL cells. Our results suggest that LPL overexpression in these cells leads to chronic metabolic adaptations that alter glucose uptake and retention. in vitro; intracellular lipid; Akt; AMP-activated protein kinase; glucose transporter doi: 10.1152/ajpendo.00618.2009.

Prolonged endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) have been linked to apoptosis via several mechanisms, including increased expression of C/EBP homologous protein (Chop). Increased long-chain fatty acids, in particular saturated fatty acids, induce ER stress, Chop expression, and apoptosis in liver cells. The first aim of the present study was to determine the role of Chop in lipid-induced hepatocyte cell death and liver injury induced by a methionine-choline-deficient diet. Albumin-bound palmitate increased Chop gene and protein expression in a dose-dependent fashion in H4IIE liver cells, siRNA-mediated silencing of Chop in H4IIE liver cells reduced thapsigargin-mediated cell death by ~40% and delayed palmitate-mediated cell death, but only at high concentrations of palmitate (400-500 [micro]M). Similar results were observed in primary hepatocytes isolated from Chop-knockout mice. Indices of liver injury were also not reduced in Chop-knockout mice provided a methionine-choline-deficient diet. To ascertain whether ER stress was linked to palmitate-induced cell death, primary hepatocytes were incubated in the absence or presence of the chemical chaperones taurine-conjugated ursodeoxycholic acid or 4-phenylbutyric acid. The presence of either of these chemical chaperones protected liver cells from palmitate-mediated ER stress and cell death, in part, via inhibition of JNK activation. These data suggest that ER stress is linked to palmitate-mediated cell death via mechanisms that include JNK activation. lipoapoptosis; unfolded protein response; nonalcoholic fatty liver disease doi:10.1152/ajpendo.00642.2009.

Accumulation of lipids in nonadipose tissues can lead to cell dysfunction and cell death, a phenomenon known as lipotoxicity. However, the signaling pathways and mechanisms linking lipid accumulation to cell death are poorly understood. The present study examined the hypothesis that saturated fatty acids disrupt endoplasmic reticulum (ER) homeostasis and promote apoptosis in liver cells via accumulation of ceramide. H4IIE liver cells were exposed to varying concentrations of saturated (palmitate or stearate) or unsaturated (oleate or linoleate) fatty acids. ER homeostasis was monitored using markers of the ER stress response pathway, including phosphorylation of IRE1[alpha] and eIF2[alpha] splicing of XBP1 mRNA, and expression of molecular chaperone (e.g., GRP78) and proapoptotic (CCAAT/enhancer-binding protein homologous protein) genes. Apoptosis was monitored using caspase activity and DNA laddering. Palmitate and stearate induced ER stress, caspase activity, and DNA laddering. Inhibition of caspase activation prevented DNA laddering. Unsaturated fatty acids did not induce ER stress or apoptosis. Saturated fatty acids increased ceramide concentration; however, inhibition of de novo ceramide synthesis did not prevent saturated fatty acid-induced ER stress and apoptosis. Unsaturated fatty acids rescued palmitate-induced ER stress and apoptosis. These data demonstrate that saturated fatty acids disrupt ER homeostasis and induce apoptosis in liver cells via mechanisms that do not involve ceramide accumulation. lipids; unfolded protein response; lipoapoptosis doi:10.1152/ajpendo.00644.2005

Fructose is a unique nutrient, due in part to its selective metabolism in the liver. Diets enriched in fructose or sucrose induce a hepatic stress response characterized by activation of c-jun N-terminal kinase. The aim of this study was to examine the regulation of c-jun N-terminal kinase by fructose in rat primary hepatocytes. Fructose was provided to rat primary hepatocytes using a fructose regenerating system, consisting of inulin and inulinase. This system provides a more physiologic delivery of fructose and avoids large disturbances in hepatocyte ATP concentrations. Fructose delivery increased c-jun N-terminal kinase activity and serine 307 phosphorylation of insulin receptor substrate-1 and reduced tyrosine phosphorylation of insulin receptor substrate-1. Activation of c-jun N-terminal kinase was maximal at a fructose concentration of 0.6 mmol/L. Fructose delivery did not increase the phosphorylation of p38 mitogen-activated protein kinase, extracellular signal regulated kinase, c-jun, or activating transcription factor-2, the latter 2 downstream nuclear targets of c-jun N-terminal kinase. However, fructose delivery increased the phosphorylation of mitogen-activated protein kinase kinase-7 (MKK7), an upstream activator of c-jun N-terminal kinase, and the association of c-jun N-terminal kinase with c-jun N-terminal kinaseinteracting protein-I, a scaffold protein that can sequester protein signaling complexes in the cytosol. These data suggest that fructose may selectively activate c-jun N-terminal kinase via regulation of MKK7 and scaffold proteins. J. Nutr. 135: 1642-1646, 2005. KEY WORDS: * rats [degrees] fiver [degrees] fructose [degrees] stress

Hepatospecific effects of fructose on c-jun N[H.sub.2]-terminal kinase: implications for hepatic insulin resistance. Am J Physiol Endocrinol Metab 287: E926-E933, 2004. First published June 15, 2004; 10.1152/ajpendo.00185.2004.--Sucrose- and fructose-enriched diets produce hepatic insulin resistance in rats independently of obesity. In humans, fructose infusion results in impaired insulin regulation of glucose production. The aim of the present study was to identify intrahepatic mediators of sucrose-and fructose-induced hepatic insulin resistance. In study 1, male rats were fed a control diet (STD, 68% of energy from corn starch, 12% from corn oil) or a sucrose-enriched diet (HSD, 68% sucrose, 12% corn oil) for 1, 2, or 5 wk. HSD produced hepatic insulin resistance at eall time points. Hepatic protein tyrosine phosphatase 1B protein levels and activity were increased at 5 wk only, whereas c-jun N[H.sub.2]-terminal kinase (JNK) activity was increased at all time points. Normalization of JNK activity in hepatocytes isolated from HSD rats improved insulin-stimulated tyrosine phosphorylation of insulin receptor substrate (IRS) proteins and insulin suppression of glucose release. In study 2, male rats were provided STD for 1 wk and then were either fasted or fasted and refed either STD or HSD for 3 or 6 h. Rats refed HSD were characterized by increased hepatic JNK activity and phosphorylation of IRS1 on [Ser.sup.307] after 6 h only. In study 3, hyperglycemic, hyperinsulinemic pancreatic clamps were performed for 3 or 6 h in the presence or absence of low or high intraportal fructose infusions. High intraportal fructose infusions, which increased portal vein fructose concentration to ~1 mM, increased hepatic JNK activity and phosphorylation of IRS1 on [Ser.sup.307] at 6 h only. These data suggest that sucrose- and fructose-induced hepatic insulin resistance are mediated, in part, via activation of JNK activity. Thus high rates of fructose metabolism in the liver appear to acutely activate stress pathways. insulin action; liver; stress; type 2 diabetes

Vagal cooling and concomitant portal norepinephrine infusion do not reduce net hepatic glucose uptake in conscious dogs. Am J Physiol Regul Integr Comp Physiol 287: R742-R748, 2004. First published May 27, 2004; 10.1152/ ajpregu.00041.2004.--We examined the role of efferent neural signaling in regulation of net hepatic glucose uptake (NHGU) in two groups of conscious dogs with hollow perfusable coils around their vagus nerves, using tracer and arteriovenous difference techniques. Somatostatin, intraportal insulin and glucagon at fourfold basal and basal rates, and intraportal glucose at 3.8 mg*[kg.sup.-1]*[min.sup.-1] were infused continuously. From 0 to 90 min [period 1 (P1], the coils were perfused with a 37[degrees]C solution. During period 2 [P2; 90-150 min in group 1 (n = 3); 90-180 min in group 2 (n = 6)], the coils were perfused with -15[degrees]C solution to eliminate vagal signaling, and the coils were subsequently perfused with 37[degrees]C solution during period 3 (P3). In addition, group 2 received an intraportal infusion of norepinephrine at 16 ng*[kg.sup.-1]*[min.sup.-1] during P2. The effectiveness of vagal suppression was demonstrated by the increase in heart rate during P2 (111 [+ or -] 17, 167 [+ or -] 16, and 105 [+ or -] 13 beats/min in group 1 and 71 [+ or -] 6, 200 [+ or -] 11, and 76 [+ or -] 6 beats/min in group 2 during P1-P3, respectively) and by prolapse of the third eyelid during P2. Arterial plasma glucose, insulin, and glucagon concentrations; hepatic blood flow; and hepatic glucose load did not change significantly during P1-P3. NHGU during P1-P3 was 2.7 [+ or -] 0.4, 4.1 [+ or -] 0.6, and 4.0 [+ or -] 1.2 mg*[kg.sup.-1]*[min.sup.-1] in group 1 and 5.0 [+ or -] 0.9, 5.6 [+ or -] 0.7, and 6.1 [+ or -] 0.9 mg*[kg.sup.-1]*[min.sup.-1] in group 2 (not significant among periods). Interruption of vagal signaling with or without intraportal infusion of norepinephrine to augment sympathetic tone did not suppress NHGU during portal glucose delivery, suggesting the portal signal stimulates NHGU independently of vagal efferent flow. vagus nerve: efferent neural transmission

The expression of glucose-6-phosphatase (G6Pase) mRNA is repressed by insulin and stimulated by cAMP and dexamethasone, with the insulin effect dominant. Both lipids and glucose increase the expression of G6Pase mRNA under conditions in which insulin is either absent or at basal levels. The aim of the present study was to investigate dietary nutrient regulation of G6Pase mRNA and protein under postprandial conditions. Male rats (n = 6-8/group) were deprived of food for 48 h and then either remained food deprived (FD) or were refed diets containing 68% cornstarch and 12% corn oil (ST; % energy), 68% sucrose and 12% corn oil (SU) or 35% cornstarch and 45% corn oil (HF) for 3 h. Rats were anesthetized, blood was drawn from the portal vein, and the liver was removed and immediately processed for subsequent analyses. Energy intake over the 3-h refeeding period did not differ among groups (209 [+ or -] 25 kJ). Portal vein glucose and insulin were 5.0 [+ or -] 0.2 mmol/L and 90 [+ or -] 18 pmol/L, respectively, in FD rats and were not significantly different among the refed groups (14.5 [+ or -] 1.2 mmol/L and 1302 [+ or -] 154 pmol/L, respectively). Compared with the FD rats, G6Pase mRNA was ~50% lower in ST and HF groups, whereas it was ~1.6 fold higher in SU-refed rats (P < 0.05). G6Pase activity in whole liver homogenates was lower in ST and HF rats than in FD and SU rats. Insulin receptor substrate (IRS) phosphorylation, IRS-association with phosphatidylinositol 3 (PI3)-kinase and activation of protein kinase B (PKB) were not significantly different among the refed groups. However, glycogen synthase kinase-3[alpha] phosphorylation was lower and cAMP response element binding protein (CREB) phosphorylation was higher in SU rats than in ST and HF refed groups. Thus, the postprandial environment after ingestion of sucrose appears to overcome the dominant effects of insulin on G6Pase mRNA, perhaps via cellular changes that reduce phosphorylation of, and therefore activate, glycogen synthase kinase-3[alpha]. KEY WORDS: * liver * glucose uptake * fructose * rats

The postprandial excursion of plasma triglyceride (TG) concentration is greater in men than in women. In this study, the disposition of dietary fat was examined in lean healthy men and women (n = 8/group) in either the overnight-fasted or fed (4.5 h after breakfast) states. A [[sup.14]C]oleate tracer was incorporated into a test meal, providing 30% of total daily energy requirements. After ingestion of the test meal, measures of arteriovenous differences in TG and [sup.14]C across the leg were combined with needle biopsies of skeletal muscle and adipose tissue and respiratory gas collections to define the role of skeletal muscle in the clearance of dietary fat. The postprandial plasma TG and [sup.14]C tracer excursions were lower (P = 0.04) in women than in men in the overnight-fasted and fed states. Women, however, had significantly greater limb uptake of total TG compared with men on both the fasted (3,849 [+ or -] 846 vs. 528 [+ or -] 221 total [micro]mol over 6 h) and fed (4,847 [+ or -] 979 vs. 1,571 [+ or -] 334 total [micro]mol over 6 h) days. This was also true for meal-derived [sup.14]C lipid uptake. [sup.14]C content of skeletal muscle tissue ([micro]Ci/g tissue) was significantly greater in women than in men 6 h after ingestion of the test meal. In contrast, [sup.14]C content of adipose tissue was not significantly different between men and women at 6 h. The main effect of nutritional state, fed vs. fasted, was to increase the postmeal glucose (P = 0.01) excursion (increase from baseline) and decrease the postmeal TG excursion (P = 0.02). These results support the notion that enhanced skeletal muscle clearance of lipoprotein TG in women contributes to their reduced postprandial TG excursion. Questions remain as to the mechanisms causing these sex-based differences in skeletal muscle TG uptake and metabolism. Furthermore, nutritional state can significantly impact postprandial metabolism in both men and women. dietary fat; gender; skeletal muscle

High-fat (HFD) and high-sucrose diets (HSD) reduce insulin suppression of glucose production in vivo, increase the capacity for gluconeogenesis in vitro, and increase glucose-6-phosphatase (G-6-Pase) activity in whole cell homogenates. The present study examined the effects of HSD and HFD on in vivo gluconeogenesis, the catalytic and glucose-6-phosphate translocase subunits of G-6-Pase, glucokinase (GK) translocation, and glucose cycling. Rats were fed a high-starch control diet (STD; 68% cornstarch), HSD (68% sucrose), or HFD (45% fat) for 7-13 days. The ratio of [sup.3]H in C6:C2 of glucose after [sup.3][H.sub.2]O injection into 6- to 8-h-fasted rats was significantly increased in HSD (0.68 [+ or -] 0.07) and HFD (0.71 [+ or -] 0.08) vs. STD (0.40 [+ or -] 0.10). G-6-Pase activity was significantly higher in HSD and HFD vs. STD in both intact and disrupted liver microsomes. HSD and HFD significantly increased the amount of the p36 catalytic subunit protein, whereas the p46 glucose-6-phosphate translocase protein was increased in HSD only. Despite increased nonglycerol gluconeogenesis and increased G-6-Pase, basal glucose and insulin levels as well as glucose production were not significantly different among groups. Hepatocyte cell suspensions were used to ascertain whether diet-induced adaptations in glucose phosphorylation and GK might serve to compensate for upregulation of G-6-Pase. Tracer-estimated glucose phosphorylation and glucose cycling (glucose [left and right arrow] glucose 6-phosphate) were significantly higher in cells isolated from HSD only. After incubation with either 5 or 20 mM glucose and no insulin, GK activity (nmol * mg [protein.sup.-1] * [main.sup.-1]) in digitonin-treated eluates (translocated GK) was significantly higher in HSD (32 [+ or -] 4 and 146 [+ or -] 6) vs. HFD (4 [+ or -] 1 and 83 [+ or -] 10) and STD (9 [+ or -] 2 and 87 [+ or -] 9). Thus short-term, chronic exposure to HSD and HFD increase in vivo gluconeogenesis and the G-6-Pase catalytic subunit. Exposure to HSD diet also leads to adaptations in glucose phosphorylation and GK translocation. glucose-6-phosphatase; liver; glucose metabolism; glucokinase

Elevated basal PI 3-kinase activity and reduced insulin signaling in sucrose-induced hepatic insulin resistance. Am J Physiol Endocrinol Metab 282: E170-E176, 2002.--Sucrose feeding reduces the ability of insulin to suppress glucose production and hepatic gluconeogenesis. The present study examined the effect of a high-sucrose diet on early insulin-signaling steps in the liver. Rats were provided a high-starch (STD, control diet) or high-sucrose diet (HSD) for 3 wk. On the day of study, overnight-fasted rats were anesthetized and injected with either saline (n = 5/diet group) or insulin (2 mU/kg, n = 5/diet group) via the portal vein. Portal venous blood and liver tissue were harvested 2 min after injections. Portal vein plasma glucose levels were not significantly different among groups, pooled average 147 [+ or -] 12 mg/dl. Western blot analysis revealed no significant differences in the amount of insulin receptor (IR), insulin receptor substrates-1 and -2 (IRS-1, IRS-2), and the p85 subunit of phosphatidylinositol (PI) 3-kinase. In contrast, the amount of the p110[beta] subunit of PI 3-kinase was increased ~2-fold in HSD vs. STD (P < 0.05). After saline injection, tyrosine phosphorylation (pY) of IR, IRS-1, and IRS-2 was not significantly different between groups. However, PI 3-kinase activity associated with phosphorylated proteins was increased ~40% in HSD vs. STD (P < 0.05). After insulin injection, pY of the IR was not different between groups, whereas pY of IRS-1 and IRS-2 was reduced (P < 0.05) in HSD vs. STD. In addition, association of IRS-1 and IRS-2 with p85 was significantly reduced in HSD vs. STD. These data demonstrate that an HSD impairs insulin-stimulated early postreceptor signaling (pY of IRS proteins, IRS interaction with p85). Furthermore, the increased amount of p110[beta] and increased basal PI 3-kinase activity suggest a diet-induced compensatory response. phosphatidylinositol 3-kinase; diet; insulin action; insulin receptor substrates; rats

Research was conducted to quantify net hepatic glucose uptake (NHGU) and hepatic glycogen synthesis during concomitant intraportal infusion of glucose and a mixture of gluconeogenic amino acids and to analyze glycogen synthesis in 42-h-fasted dogs. Results indicate that intraportal gluconeogenic amino acid infusion directed glucose carbon away from the liver. Also, there was equivalent net hepatic carbon uptake whether or not an infusion of amino acid was conducted.

Research shows that diet-induced insulin resistance is halted by menhaden fish oil. Menhaden oil does not have the same influence over insulin activity when sucrose insulin-resistance is already in existence. Experiments using male Wistar rats that had eaten 68% starch in their diet compared with male Wistar rats that had eaten 68% sucrose in their diet are described.

The effect of female sex steroid hormones on the progression of sucrose-induced insulin resistance was analyzed in female rats subjected to high-sucrose feeding. Female Wistar rats fed on a high-sucrose diet did not exhibit changes in the levels of basal glucose, glucose infusion rate and clamp rate of glucose appearance compared to female rats fed on high-starch diets. Furthermore, sucrose- and starch-fed animals did not exhibit differences in plasma glycogen and tissue triglycerides.

The role of insulin action on glucose kinetics in response to high fat diets (HFD) was analyzed in dietary obesity-sensitive (AKR/J) mice strains to determine the relationship between insulin and body weight regulation. Body weight gain and fat pad weight in AKR/J mice on HFD were influenced by insulin action on the rate of glucose appearance. Furthermore, hepatic insulin resistance did reduce HFD-induced weight gain. However, selective hepatic insulin resistance increased weight gain in AKR/J mice.

The effect of high-sucrose diet on hepatic glucose production and the contribution of hepatic gluconeogenesis on sucrose-induced hepatic insulin resistance were analyzed in single-pass rodent liver perfusions. Analysis of isolated livers from rats after sucrose feeding indicated the presence of increased hepatic gluconeogenesis. The sucrose-mediated increase in intrinsic capacity for gluconeogenesis interfered with insulin suppression of the gluconeogenic pathway.

High-fat diet-induced obesity in male Wistar rats was analyzed to determine the alterations in the enzymatic profile of the gastrocnemius muscle, heart and liver in relation to obesity. Analysis of heart, liver and gastrocnemius muscles from Wistar rats exhibiting high-fat diet-induced obesity indicated the presence of a tissue enzymatic profile that favors carbohydrate usage. Furthermore, obese rats exhibited continuous increase in energy intake which contributed to body weight gain after a regimen of high-fat diet.

The effect of high-sucrose diets on hepatic and peripheral insulin action was investigated in rats. The animals were fed a high-starch diet (ST), followed by a high-sucrose diet (SU), and were monitored for changes in body weight, percent body fat, glucose appearance, and glycogen synthesis. ST and SU rats showed no differences in body weight, percent body fat, and liver fatty acid. SU rats showed reduced glucose appearance and muscle glycogen synthesis and increased fasting plasma triglyceride (TG). The results suggest that sucrose feeding induces insulin resistance and that TG is associated with insulin resistance.

The net hepatic glucose uptake is greater during glucose infusion through the portal vein of dogs rather than the peripheral vein. The absence of liver nerves reduces glycogen level during glucose infusion. Hepatic denervation fails to affect the proportion of glycogen deposited through direct pathways, and net hepatic glycogen synthesis during peripheral glucose infusion. Sympathetic stimulation decreases hepatic glycogen levels and increases blood glucose level, while parasympathetic stimulation has an opposite effect.

Insulin resistance is produced, without much change in body composition, by diets containing low or high quantities of sucrose. Time course of induction and tissue distribution of insulin resistance are changed by dietary sucrose quantity. Liver and muscle insulin resistance occurs within an 8-wk period for a high-sucrose diet and 16-wk period for a low-sucrose diet. Insulin resistance due to low-sucrose usually occurs in liver.

Experiments to determine the time course of adaptation of male obesity-prone (OP) and obesity-resistant (OR) rats to a high-fat diet show that early adaptations determine the development of obesity-resistant or obesity-prone properties. Variations in the fat and body weights of OR and OR rats are not a result of fat-accumulation in the epididymal or retroperitoneal fat depots. Lipoprotein lipase (LPL) mRNA functions are greater in epididymal fat pad and lower in gastrocnemius muscle of OP and OR rats, indicating that this protein mediates fat accumulation in the fat pads. However, the overall LPL mRNA activity is less in low fat diet-fed rats than in high fat diet-fed rats.

A high-sucrose diet enhances hepatic and skeletal muscle insulin resistance that is attributed to low skeletal muscle glycogen synthesis and high hepatic phosphoenolpyruvate carboxykinase activity. A model is developed to analyze the effect of macronutrient diet content on insulin action under normoglycemic conditions.

Use of the arteriovenous (AV) difference technique to study the disposition of a mixed meal in 13 conscious dogs fasted for 24 hours reveals that enough carbon is released by the hepatic intake of gluconeogenic and glucose substrates for the generation of CO2 and lactate, and for hepatic synthesis of glycogen. Some of the gluconeogenic carbon absorbed by the liver after the meal is released by the peripheral tissues.

The hepatic nerves can modulate hepatic glycogenolysis and glycogenesis and thus might be expected to be involved in the response of the animal to the transition from the fed to the food-deprived state. Therefore the arterial concentrations and net hepatic balance of glucose and its metabolites, as well as the hepatic glycogen concentrations, were compared in hepatic-innervated and -denervated dogs 18, 24 and 42 h after their usual daily meal. Arterial concentrations of glucose, alanine, lactate and glycerol; net hepatic balances of glucose, alanine and glycerol; and glycogen concentrations were similar in hepatic-innervated and -denervated dogs at each time investigated. Net hepatic balances of lactate (with negative values indicating uptake) in hepatic-innervated and -denervated dogs, respectively, were: 18 h, 4.1 +/- 4.3 vs. -4.3 +/- 3.6 microns mol center dot kg to the -1 center dot min to the -1; 24 h, 4.8 +/- 3.6 vs. -6.7 +/- 1.7 micron mol center dot kg to the -1 center dot min to the -1 (P < 0.05); 42 h, -7.0 +/- 2.0 vs. -6.8 +/- 1.0 micron mol center dot kg to the -1 center dot min to the -1. Based on changes in net hepatic lactate balance, the denervated liver responds more rapidly to food deprivation than the innervated liver, but the metabolic state of the liver appears similar by 42 h after a meal.

Studies were conducted to establish the status of carbon within the denervated liver during glucose addition, and to determine if hepatic denervation changed the net mass of hepatic glycogen produced or the predominant pathway of hepatic glycogen preparation. It was observed that the glycemic response and level of total glycogen preparation during intraduodenal glucose infusion did not differ in hepatic denervated and hepatic innervated dogs.

Skeletal muscle fuel, metabolism and gain in weight in rats regulate their heterogeneous response to a high-fat (HF) diet. Obesity prone (OP) rats or a HF diet for over a month, experience enhanced resistance to insulin. The study of glucose oxidation and insulin-stimulated glucose uptake reveals reduced glucogen synthesis in OP rats. Obesity resistant (OR) animals do not exhibit this reduction. No substantial difference in muscle triglyceride between OP and OP rats is recorded. Skeletal muscle glucose induction in OP rats is significantly imperfect.