Rates of gluconeogenesis in perfused liver of alloxan-diabetic fed rats

The maximal capacity of the liver to produce glucose was examined using a technique, which permited to investigate gluconeogenesis in diabetic fed rats. Diabetes was obtained with an iv injection of alloxan (40 mg/kg). Livers from diabetic fed rats were perfused in situ and gluconeogenesis from different glucose precursors were measured one week after alloxan injection. Hepatic gluconeogenesis from L-alanine (5 mM) was absent. However, increased urea, pyruvate and L-lactate production was observed during L-alanine infusion. Differently of L-alanine, alloxan-diabetic fed rats showed increased hepatic glucose production from pyruvate (5 mM), L-lactate (2 mM) and D-frutose (5 mM). Additionally, increased L-lactate production from pyruvate and pyruvate production from L-lactate were observed. However, pyruvate production from L-lactate was lower in the diabetic group when compared with control group. Moreover similar tendency were observed for L-alanine and D-frutose. Taken together our results demonstrate influence of the cytosolic redox potential (NADH/NAD+ ratio) in the metabolic fate L-alanine. Additionally, in contrast to L-alanine, diabetic rats not only showed increased rate of glucose production from L-glutamine (5 mM) but also higher values than control rats.     

Changes in glycemia induced by exercise in rats: contribution of hepatic glycogenolysis and gluconeogenesis

The participation of hepatic glycogenolysis and gluconeogenesis to the glycemic changes promoted by exercise was investigated. For this purpose, we employed swimming rats (2.5% body weight extra load attached to the tail, at 24 degrees C) using a favorable condition to measure hepatic glycogenolysis (fed rats) and a favorable condition to measure hepatic gluconeogenesis (fasted rats). This experimental approach permits us to compare the contribution of hepatic glycogenolysis and gluconeogenesis to glucose changes for a specific schedule of exercise. The animals were investigated at rest, after 5 minutes of swimming and after swimming to exhaustion. Our results show that hepatic glycogen has a crucial role to determine hyperglycemia during exercise. In contrast, hypoglycemia developed during exercise when glycogen was depleted. However, the ability of the liver to produce glucose from L-lactate, glycerol and L-glutamine was increased during exercise. Taken together, these findings suggest that the hepatic capacity to produce glucose from gluconeogenic substrates (except for L-alanine) was increased when hepatic glycogen stores were depleted. Thus, the increased capacity to produce glucose shown by livers from exercising rats must to be an important metabolic adaptation to protect against severe hypoglycemia.     

Differential effects of epinephrine on glucose production and disposal in man.

Normal subjects were infused 1) with epinephrine (50 ng/(kg.min)) for 180 min followed by epinephrine plus glucagon (3 ng/(kg.min)) for 60 min after which the epinephrine infusion rate was increased (125 ng/(kg.min)) or 2) with epinephrine plus somatostatin (500 microgram/h) for 180 min. Epinephrine increased glucose production and plasma glucagon transiently but caused persistent suppression of glucose clearance and sustained hyperglycemia (despite increased plasma insulin and gluconeogenic substrates); glucose production increased again on addition of glucagon and on increasing the epinephrine infusion rate. During epinephrine plus somatostatin, glucose production still increased transiently, but further suppression of glucose clearance caused more marked hyperglycemia. In conclusion, 1) in man hyperepinephrinemia within the physiological range caused sustained suppression of glucose clearance but only a transient increase in glucose production; 2) this transient hepatic response a) was not due to glycogen or substrate depletion, b) occurred without changes in plasma glucagon or insulin, c) was specific for epinephrine but permitted subsequent responses to changes in plasma epinephrine; 3) epinephrine can serve as a physiological regulator of glucose homeostasis in man both by increasing glucose production and by decreasing glucose clearance.     

Undernutrition during early lactation period induces metabolic imprinting leading to glucose homeostasis alteration in aged rats

This study examines the effects of early postnatal undernutrition on the glucose homeostasis of rats at one year of age, comparing the effects of a free protein diet (FPD) and a normal diet containing 25% of protein (NPD) supplied during the first 10 days of lactation. The insulin secretion and the insulin sensitivity, using the glucose clamp technique, were studied in these rats. The analysis of the integrated area of insulin secreted by isolated islets stimulated with 16.7 mM glucose was reduced in the FPD group when compared with the NPD (FPD = 5.07 +/- 1.6 ng/ml/50 min.; NPD = 35.8 +/- 12 ng/ml/50 min., p < or = 0.001). Using the glucose clamp technique the plasma glucose concentration was raised by continuous glucose stimulation with 10 mg/Kg(-1) x min(-1). After 30 minutes the NPD displayed a lower level of plasma glucose concentration (FPD = 220.8 +/- 8 mg/dl.; NPD = 185 +/- 3 mg/dl., p < or = 0.01). Afterwards, the hyperglycemia of the NPD increased and in both groups was, subsequently, similarly maintained and, after 90 minutes of continuously glucose infusion, there was no difference between the groups (FPD = 191.6 +/- 8 mg/dl.; NPD = 189.3 +/- 17 mg/dl). In order to test the peripheral sensitivity to glucose, insulin 1.67 mU x Kg(-1) min(-1) was administered together with glucose 10 mg x kg(-1) x min(-1) (50 minutes after the beginning of the clamping). The glycemia after the insulin administration compared to glycemia 90 minutes of FPD was significantly reduced and the NPD maintained the same glycemic level ( FPD from 220.7 +/- 8 mg/dl to 170.6 +/- 5 mg/dl, p < or = 0.001; NPD from 195.3 +/- 10 mg/dl to 185.2 +/- 6 mg/dl.). Also, after the insulin administration the plasmatic insulin was raised but after 90 minutes the FPD group displayed a lower insulin concentration when compared to the same point of time for the NPD group (FPD = 0.8 +/- 0.01 ng/ml; NPD = 1.8 +/- 0.03 ng/ml., p < or = 0.01). The data suggest that undernutrition during early postnatal may cause a metabolic imprinting which leads to a decreasing action of the insulin secretory apparatus and increased insulin sensitivity as an adaptive response.     

Lack of influence of glucagon on glucose homeostasis after prolonged exercise in rats

Summary The significance of glucagon for post-exercise glucose homeostasis has been studied in rats fasted overnight. Immediately after exhaustive swimming either rabbit-antiglucagon serum or normal rabbit serum was injected by cardiac puncture. Cardiac blood and samples of liver and muscle tissue were collected before exercise and repeatedly during a 120 min recovery period after exercise. During the post-exercise period plasma glucagon concentrations decreased but remained above pre-exercise values in rats treated with normal serum, while rats treated with antiglucagon serum had excess antibody in plasma throughout. Nevertheless, all other parameters measured showed similar changes in the two groups. Thus after exercise the grossly diminished hepatic glycogen concentrations remained constant, while the decreased blood glucose concentrations were partially restored. Simultaneously concentrations in blood and serum of the main gluconeogenic substrates, lactate, pyruvate, alanine and glycerol declined markedly. During the post-exercise period NEFA concentrations in serum and plasma insulin concentrations remained increased and decreased, respectively, while plasma catecholamines did not differ from basal values. Muscle glycogen concentrations decreased slightly. These findings suggest that in the recovery period after exhaustive exercise the increased glucagon concentrations in plasma do not influence gluconeogenesis.     

Effect of in vivo exposure to insulin on glucose metabolism in rat aorta

The effect of administration of insulin in vivo on accumulation of [14C]glucose carbon in rat aorta in vitro was studied. Insulin was injected intravenously in a tail vein 5-60 min before the rats were killed and the accumulation of [14C]glucose was determined after incubation for 30-120 min in 5.6 mM [14C]glucose. When determined 30 min after injection of insulin (4 U kg-1) the aortic [14C]glucose incorporation was significantly increased when an incubation period of 120 min was used, while no significant effect was found after incubation for 30 or 60 min. In subsequent experiments an incubation time of 120 min was used. The aortic [14C]glucose accumulation was not increased when determined 5 or 60 min after injection of insulin (4 U kg-1). Injection of insulin (2 U kg-1) 5 or 30 min before the rats were killed had no effect on the aortic [14C]glucose accumulation but it had a pronounced effect on [14C]glucose accumulation in rat diaphragm. Serum insulin determined 30 min after injection of insulin (2 U kg-1) was 731 +/- 58 mU-1 and in saline-treated control rats 37 +/- 3 mU l-1. These results suggest that the glucose metabolism of vascular smooth muscle has a low sensitivity to the immediate effects of insulin.     

On the mechanism of glucagon stimulation of hepatic gluconeogenesis

Summary The addition of L-alanine as substrate to a perfused rat liver preparation produced a five-fold increase in the rate of glucose production. This enhancement of the gluconeogenic flux seems to be a consequence of a rise in the steady-state levels of pyruvate and oxaloacetate subsequent to the rise in alanine concentration.Glucagon (2×10^–9 M) increased the gluconeogenic flux from alanine (10 mM) by 50 percent, even though the concentration of the substrate in the perfusion fluid was at saturation. This effect was accompanied by a rise in the intracellular concentrations of alanine. However, the steady-state concentrations of pyruvate and oxaloacetate were decreased, probably as a consequence of a more reduced state of the nicotinamide-nucleotide system. In vivo, the intraperitoneal administration of glucagon to starved rats was accompanied by a decrease in the hepatic alanine and pyruvate concentrations despite the striking effects raising the plasma glucose levels. These observations seem to indicate that the effect of the hormone increasing the hepatic glucose output must be mediated through some other mechanism(s) independent of the intracellular variations in the hepatic amino acids levels.     

Hepatic gluconeogenesis and Krebs cycle fluxes in a CCl4 model of acute liver failure

Acute liver failure was induced in rats by CCl4 administration and its effects on the hepatic Krebs cycle and gluconeogenic fluxes were evaluated in situ by 13C NMR isotopomer analysis of hepatic glucose following infusion of [U-13C]propionate. In fed animals, CCl4 injury caused a significant increase in relative gluconeogenic flux from 0.80+/-0.10 to 1.34 +/-0.24 times the flux through citrate synthase (p<0.01). In 24-h fasted animals, CCl4-injury also significantly increased relative gluconeogenic flux from 1.36+/-0.16 to 1.80+/-0.22 times the flux through citrate synthase (p<0.01). Recycling of PEP via pyruvate and oxaloacetate was extensive under all conditions and was not significantly altered by CCl4 injury. CCl4 injury significantly reduced hepatic glucose output by 26% (42.8+/-7.3 vs 58.1+/-2.4 micromol/kg/min, p=0.005), which was attributed to a 26% decrease in absolute gluconeogenic flux from PEP (85.6+/-14.6 vs 116+/-4.8 micromol/kg/min, p<0.01). These changes were accompanied by a 47% reduction in absolute citrate synthase flux (90.6+/-8.0 to 47.6+/-8.0 micromol/kg/min, p<0.005), indicating that oxidative Krebs cycle flux was more susceptible to CCl4 injury. The reduction in absolute fluxes indicate a significant loss of hepatic metabolic capacity, while the significant increases in relative gluconeogenic fluxes suggest a reorganization of metabolic activity towards preserving hepatic glucose output.     

Hepatic vagotomy does not alter plasma insulin response to a low dose injection of glucose.

It has been reported that insulin concentration is altered by a hepatic vagotomy following intraperitoneal glucose injection (0.3 g/kg) resulting in supraphysiological blood glucose concentrations. On the other hand, neural activity of the hepatic vagus nerve has been shown to be substantially reduced by lower doses (0.05 g/kg intraportal; 0.1 g/kg intravenous). The present study was conducted in order to examine the role of the hepatic vagus nerve in insulin response after intraperitoneal injections of 0.1 and 0.3 g/kg of glucose. Measurements were made 5 days after section of this branch. In a first experiment, arterial glucose and insulin concentrations were not affected by the hepatic vagotomy following injections of either 0.1 or 0.3 g/kg of glucose. The same finding was also found in a second experiment in which portal glucose and insulin levels were measured after injection of 0.1 g/kg of glucose. These results suggest that large changes in neural activity are needed for the hepatic vagus nerve to influence the insulin response.     

L-谷氨酰胺与肝脏大部分切除后的再生

背景：L-谷氨酰胺作为DNA和谷胱甘肽等合成的氮前体,在肝组织再生,肝细胞增殖的过程中扮演着极其重要的角色。 目的：观察经饮食由来补充L-谷氨酰胺对大鼠肝脏大部切除后肝再生能力的影响。 方法：Wistar大鼠随机分组3组,L-谷氨酰胺组和L-丙氨酸组大鼠肝切除前分别灌服10% L-谷氨酰胺或10%L-丙氨酸,肝切除后继续加入饮用水中饮用,对照组肝切除前后均使用饮用水。 结果与结论：大鼠肝切除后72 h L-谷氨酰胺组肝再生率明显高于对照组及L-丙氨酸组(P < 0.05)。肝切除后24 h和72 h L-谷氨酰胺组肝细胞增殖均明显高于对照组和L-丙氨酸组(P < 0.01;P < 0.05)。肝切除后24 h和72 h总RNA水平在两种氨基酸与对照组之间差异无显著性意义。肝切除后72 h基因组DNA的含量L-谷氨酰胺组显著高于对照组和L-丙氨酸组 (P < 0.05)。提示肝损伤围手术期投用高浓度L-谷氨酰胺对大鼠肝再生有促进作用,而投用L-丙氨酸则没有此作用。     

Control of hepatic glycogen metabolism in the rhesus monkey: effect of glucose, insulin, and glucagon administration.

The effects of intravenous glucose, insulin and glucagon admininistration on the hepatic glycogen synthase and glycogen phosphorylase systems were assessed in the anesthetized rhesus monkey. Results were correlated with measurements of hepatic cyclic AMP (cAMP) concentrations and plasma glucose, insulin, and glucagon concentrations. Both glucose and insulin administration promoted significant inactivation of phosphorylase by 1 min, which was followed by more gradual activation of synthase. Neither glucose nor insulin caused significant changes in hepatic cAMP. Marked hyperglucagonemia resulting from insulin-induced hypoglycemia did not cause increases IN in hepatic cAMP, suggesting that the elevated insulin levels possibly inhibited glucagon action on the hepatic adenylate cyclase-cAMP system. Glucagon administration caused large increases in hepatic cAMP and activation of phosphorylase within 1 min, followed by more gradual inactivation of synthase when it had been previously activated by glucose. Concomitant glucose infusion, with resulting increased plasma insulin concentrations, markedly diminished the duration of hepatic cAMP elevations following glucagon adminstration, again suggesting an insulin inhibition of glucagon action on the hepatic adenylate-cAMP system.     

Impaired biphasic insulin release in mildly diabetic rats bearing a chronic portal vein catheter.

Using a new technique of chronic portal vein catheterization in freely moving rats, we investigated the insulin release to intravenous (IV) glucose (0.5 g/kg) injection in mildly diabetic (35 mg/kg streptozotocin, IV) rats. In nondiabetic rats, plasma insulin of the portal vein showed a clear biphasic release pattern, which peaked within two min after glucose injection, reached a nadir between three and six min, then began to rise to a second peak between 7 and 10 min, and reached a second nadir at 14 min. In mildly diabetic rats, a biphasic insulin release was evident, but both the first and the second phase insulin releases were impaired. In spite of this impaired insulin release, glucose intolerance was mild. Simultaneous blood sampling from the portal and peripheral veins after IV glucose injection revealed that diabetic rats showed diminished hepatic insulin extraction. These results suggest that the biphasic insulin release to glucose is impaired in mildly diabetic rats, but diminished hepatic insulin extraction contributes at least to keeping glucose tolerance mild.     

Integration of [U-13C]glucose and 2H2O for quantification of hepatic glucose production and gluconeogenesis

Glucose metabolism in five healthy subjects fasted for 16 h was measured with a combination of [U-13C]glucose and 2H2O tracers. Phenylbutyric acid was also provided to sample hepatic glutamine for the presence of 13C-isotopomers derived from the incorporation of [U-13C]glucose products into the hepatic Krebs cycle. Glucose production (GP) was quantified by 13C NMR analysis of the monoacetone derivative of plasma glucose following a primed infusion of [U-13C]glucose and provided reasonable estimates (1.90 +/- 0.19 mg/kg/min with a range of 1.60-2.15 mg/kg/min). The same derivative yielded measurements of plasma glucose 2H-enrichment from 2H2O by 2H NMR from which the contribution of glycogenolytic and gluconeogenic fluxes to GP was obtained (0.87 +/- 0.14 and 1.03 +/- 0.10 mg/kg/min, respectively). Hepatic glutamine 13C-isotopomers representing multiply-enriched oxaloacetate and [U-13C]acetyl-CoA were identified as multiplets in the 13C NMR signals of the glutamine moiety of urinary phenylacetylglutamine, demonstrating entry of the [U-13C]glucose tracer into both oxidative and anaplerotic pathways of the hepatic Krebs cycle. These isotopomers contributed 0.1-0.2% excess enrichment to carbons 2 and 3 and approximately 0.05% to carbon 4 of glutamine.     

Comparison of the effects of pre-exercise feeding of glucose,glycerol and placebo on endurance and fuel homeostasis in man

Summary Six men were studied during exercise to exhaustion on a cycle ergometer at 73% of following ingestion of glycerol, glucose or placebo. Five of the subjects exercised for longer on the glucose trial compared to the placebo trial (p<0.1; 108.8 vs 95.9 min). Exercise time to exhaustion on the glucose trial was longer (p<0.01) than on the glycerol trial (86.0 min). No difference in performance was found between the glycerol and placebo trials. The ingestion of glucose (lg · kg^–1 body weight) 45 min before exercise produced a 50% rise in blood glucose and a 3-fold rise in plasma insulin at zero min of exercise. Total carbohydrate oxidation was increased by 26% compared to placebo and none of the subjects exhibited a fall in blood glucose below 4 mmol · l^–1 during the exercise. The ingestion of glycerol (lg · kg^–1 body weight) 45 min before exercise produced a 340-fold increase in blood glycerol concentration at zero min of exercise, but did not affect resting blood glucose or plasma insulin levels; blood glucose levels were up to 14% higher (p<0.05) in the later stages of exercise and at exhaustion compared to the placebo or glucose trials. Both glycerol and glucose feedings lowered the magnitude of the rise in plasma FFA during exercise compared to placebo. Levels of blood lactate and alanine during exercise were not different on the 3 dietary treatments. These data contrast with previous reports that have indicated glucose feeding pre-exercise produces hypoglycaemia during strenuous submaximal exercise and reduces endurance performance. It appears that man cannot use glycerol as a gluconeogenic substrate rapidly enough to serve as a major energy source during this type of exercise.     

Effect of adrenaline on exchange of glucose in leg tissues and splanchnic area. A comparison with the metabolic response to surgical stress

Surgical trauma is accompanied by increased energy expenditure and raised arterial concentrations of adrenaline and glucose. In order to study the acute effects of an adrenaline infusion on glucose metabolism and oxygen uptake in the leg and splanchnic bed, adrenaline was administered at a rate giving plasma concentrations of adrenaline similar to those in connection with abdominal surgery. Seven healthy males participated in the study. Adrenaline 40 ng/(min X kg body weight) (0.22 nmol/(min X kg body weight] was infused producing a plasma concentration of 2.77 +/- 0.42 nmol/l (mean +/- SEM). Leg and splanchnic blood flows and the femoral and hepatic arterio-venous differences for oxygen, glucose, lactate and other metabolites were determined. Measurements were made before and between 30 and 40 min after the start of the adrenaline infusion. Following the infusion of adrenaline the leg blood flow increased by 140% and hepatic blood flow by 25%. The leg oxygen uptake increased by 30%, but no significant increase in splanchnic oxygen uptake was observed. The arterial glucose concentration rose by 35%. Splanchnic glucose output increased X 2.5, but no significant increase in leg glucose uptake was observed. Leg release of gluconeogenic substrates increased but only lactate and glycerol uptake increased in the splanchnic bed. Leg blood flow increased more than that usually seen after surgery, whereas leg oxygen uptake and splanchnic oxygen uptake was higher in the immediate postoperative period. Splanchnic glucose release increased more during the infusion than in connection with surgery. It is concluded that adrenaline at a plasma concentration similar to that during and immediately after surgery can induce changes in glucose metabolism which are of the same order or more pronounced than those seen in connection with abdominal surgery.     

A new glucose clamp algorithm: clinical validation

A new glucose clamp technique for in vivo studies of insulin sensitivity was validated clinically. Eighteen patients (10 males, 8 females, age 35-80 years, body mass index 34.6-17.04) were connected to a computer-assisted artificial pancreas "Betalike R", using a new algorithm based on a "minimal model", to carry out the glucose clamp technique automatically and especially to overcome the well-known problems of its priming phase. We performed the euglycemic hyperinsulinemic clamp in four patients and the hyperglycemic hyperinsulinemic clamp in 14. In one patient both clamps were done. The mean priming time to reach steady-state glycemia was 20 min. Plasma insulin concentrations were measured every 20 min. This new automatic glucose clamp technique enables the priming phase to be run without any significant overshoot, and accidental variations of glycemia in steady state were reduced to a minimum. The system showed satisfactory safety and stability in controlling the patient's glycemia and assured high speed of the priming phase.     

磷酸二酯酶抑制剂诱导的大鼠胰岛素抵抗对糖脂代谢的影响

目的:探讨选择性磷酸二酯酶III(PDE₃)抑制剂米力农(milrinone)对大鼠胰岛素分泌、血糖、血浆游离脂肪酸(FFA)的影响和剂量依赖关系,及其在胰岛素钳夹状态下对大鼠糖代谢和胰岛素敏感性的影响。方法:由植入导管给予大鼠不同剂量的米力农(1、5、25μmol/kg)在不同时相测定血糖、血浆FFA和胰岛素水平并与对照组比较。在清醒状态下建立大鼠高胰岛素-正常血糖钳夹技术,并在钳夹120min时分别经导管给予米力农(25μmol/kg)和25%二甲基亚砜(DMSO,对照组)。采用气相色谱-质谱仪(GC-MS)测定糖代谢率。结果:3个不同剂量米力农组血浆FFA浓度明显高于对照组和给药前,在注射后2min,各组FFA升高的百分数为:50%、52%、55%(1、5、25μmol/kg)。在5、25μmol/kg组血浆胰岛素水平也明显高于对照组和给药前,仅25μmol/kg组血糖浓度高于对照组和给药前。在胰岛素钳夹研究中,米力农处理组大鼠血浆FFA明显高于给药前,肝糖输出(HGP)也明显高于给药前。葡萄糖输注率(GIR)明显低于对照组和给药前。结论:米力农损害了胰岛素抑制脂解和肝糖输出的能力及胰岛素介导的外周组织糖的利用。因此,米力农处理可能在体内诱导了一个急性胰岛素抵抗。     

Increase of food intake induced by glucagon in the rat

The effect of intraperitoneal administration of saline, glucose (25 mg/100 g b.w.), insulin (0.025 U/100 g b.w.) and glucagon (50 micrograms/kg b.w.) on glycemia, liver glycogen concentration and food intake was studied on 104 male adult Wistar rats. When saline was injected the amount of food ingested was similar to that expected at the metabolic moment selected for the tests. Glucose administration did not reduce food intake but both insulin and glucagon provoked a threefold increase during the 60 minutes ensuing the injection. The overall ingestion of food during the 24 hours after the injection of the hormones was significantly higher (about 10%) than the control values during the preceding or the succeeding 24 hours. A hyperphagic, rather than a hypophagic effect of glucagon administration is possibly related to the small dose used in the experiments. The mechanisms involved in the increase of food intake due to glucagon are discussed in terms of acceleration of the metabolic reactions that normally prevent large drops of glycemia as glucose utilization proceeds during the inter-meal periods and that in physiological conditions build up until the need for food arises.     

Unidirectional transport of glucose and lactate into brain of fetal sheep and guinea-pig

The first-passage multiple-indicator dilution method was used to measure blood to brain transport of D- and L-glucose, D- and L-lactate and sucrose relative to 22Na, an impermeable reference tracer, in fetal sheep. Fractional extraction for D-glucose was 0.315 +/- 0.051 (S.E.M.) at normal glucose levels and fell to 0.198 +/- 0.041 at 5.2 +/- 0.4 mM-glucose. Fractional extractions for L-glucose, D- and L-lactate and sucrose were not different from zero. No specific blood-brain transport system was detected for L-lactate in fetal sheep in vivo (fractional extraction = -0.024 +/- 0.019). Uptake of L-lactate into isolated microvessels from fetal sheep cerebrum in vitro showed a slightly higher rate (32.2 +/- 8.9 pmol min-1 (mg protein)-1) than that for D-lactate (22.6 +/- 5.6). In fetal guinea-pigs, the carotid arterial injection method with tritiated water as the permeable reference was used to measure the brain uptake index (BUI). BUI was determined for D-glucose (0.304 +/- 0.065) sucrose (0.008 +/- 0.001), L-lactate (0.418 +/- 0.112) and D-lactate (0.071 +/- 0.024). Unidirectional influx calculated from these measurements and estimates of cerebral blood flow showed that transport would be rate-limiting for cerebral glucose utilization at arterial glucose levels below 0.5 mM in fetal sheep and 1.7 mM in fetal guinea-pig. In fetal sheep, but not in fetal guinea-pigs, lactate efflux may be limited by brain-blood transport.     

Effect of hepatic vagotomy and/or coeliac ganglionectomy on the delayed eating response to insulin and 2DG injection in rats

The eating response that occurs following recovery from the effects of insulin or 2-deoxy-D-glucose (2DG) injection was examined in rats with hepatic vagotomy and/or coeliac ganglionectomy. Rats were deprived of food and injected with either saline (1 ml/kg), regular insulin (3 U/kg) or 2DG (200 mg/kg). Plasma glucose was measured periodically over the next 6 hr and then food was returned and intakes were measured over the next 2 hr. Rats increased food intake 6–8 hr after insulin or 2DG injection compared to the saline (control) condition. Nerve section did not affect the plasma glucose or food intake responses to insulin or 2DG injection. The results indicate that the innervation of the liver via the vagus nerve or coeliac ganglion is not involved in the delayed eating response to insulin and 2DG injection.