Acute non-insulin-like stimulation of rat muscle glucose metabolism by troglitazone in vitro

1. The direct short-term effects of troglitazone on parameters of glucose metabolism were investigated in rat soleus muscle strips. 2. In muscle strips from Sprague-Dawley rats, troglitazone (3.25 micromol l(-1)) increased basal and insulin-stimulated glucose transport by 24% and 41%, respectively (P<0.01 each). 3. In the presence of 5 nmol l(-1) insulin, stimulation of glucose transport by 3.25 micromol l(-1) troglitazone was accompanied by a 36% decrease in glycogen synthesis, while glycolysis was increased (112% increase in lactate production) suggesting a catabolic response of intracellular glucose handling. 4. Whereas insulin retained its stimulant effect on [3H]-2-deoxy-glucose transport in hypoxia-stimulated muscle (by 44%; c.p.m. mg(-1) h(-1): 852+/-77 vs 1229+/-75, P<0.01), 3.25 micromol l(-1) troglitazone failed to increase glucose transport under hypoxic conditions (789+/-40 vs 815+/-28, NS) suggesting that hypoxia and troglitazone address a similar, non-insulin-like mechanism. 5. No differences between troglitazone and hypoxia were identified in respective interactions with insulin. 6. Troglitazone acutely stimulated muscle glucose metabolism in a hypoxia/contraction-like manner, but it remains to be elucidated whether this contributes to the long-term antidiabetic and insulin enhancing potential in vivo or is to be regarded as an independent pharmacological effect.     

Effects of a sympathetic activation by a lower body negative pressure on glucose and lipid metabolism

The effects of a sympathetic activation elicited by a lower body negative pressure (LBNP) (at -15 mmHg for 75 min) were assessed in 7 healthy subjects on two occasions: (i) in post-absorptive conditions, and (ii) during glucose infusion (22.2 mumol kg-1 min-1). LBNP increased plasma norepinephrine concentration and heart rate. It did not alter whole-body glucose metabolism (measured with [6,6-2H]glucose) and glycerol turnover (measured with [1,1,2,3,3-2H]glycerol). Interstitial glycerol concentrations were monitored with microdialysis in subcutaneous adipose tissue and in skeletal muscle. LBNP increased dialysate glycerol concentrations in muscle by 16% (P < 0.03) but not in adipose tissue in post-absorptive conditions, and by 37% in adipose tissue (P < 0.05) but not in muscle during glucose infusion. These results indicate that an LBNP-induced sympathetic activation (i) does not increase endogenous glucose production, and (ii) induces only a slight stimulation of lipolysis in adipose tissue during glucose infusion.     

Effects of the endogenous clock and sleep time on melatonin, insulin, glucose and lipid metabolism

Annexins are a unique family of membrane-associated, Ca2+ and phospholipid-binding proteins found in various tissues. Among the 12 isoforms, Annexin II, V and VI exist in heart tissue in the highest amounts. Annexin VI has been shown to affect intracellular Ca2+ cycling and contractility in isolated cardiomyocytes. Annexin V is present in both cardiomyocytes and non-myocyte cell types in the heart and may play a role in the regulation of cellular ion fluxes, organization and secretion, while the cardiac effects of annexin II are unclear. To identify changes in annexin II, V and VI isoforms that might occur in human heart failure, we measured mRNA and protein levels of these three annexins in transplanted left ventricular tissue of 12 patients with end-stage congestive heart failure due to coronary artery disease (CAD, n=6) or idiopathic dilated cardiomyopathy (DCM, n=6) who underwent cardiac transplantation. Normal heart tissue (C, n=6) was used as a control. Northern blot analyses showed a significant decrease (61%) in annexin VI mRNA levels in heart failure patients compared with controls (1.08+/-0.16 v 2.79+/-0.20 A.U.C. unit, determined by laser densitometry, mean+/-s.e.). In contrast, we found a 67% increase (2. 32+/-0.27 v 3.88+/-0.29) in annexin II mRNA levels and a two-fold increase (1.00+/-0.24 v 2.21+/-0.29) in annexin V mRNA levels in cardiomyopathic hearts as compared to normal hearts. Western blot analyses demonstrated a corresponding decrease (46.1%) in annexin VI protein levels in the heart failure group as compared to controls (2. 63+/-0.22 v 4.88+/-0.52), while annexin II protein levels showed a significant 40.7% increase in patients with heart failure compared to those in normal hearts (5.08+/-0.67 v 3.61+/-0.32). Annexin V protein levels were also significantly increased (45%) in heart failure patients compared with normal (2.14+/-0.19 v 1.48+/-0.11). No difference in either annexins II, V or VI mRNA and protein levels were found between CAD and DCM patients. We conclude that human end-stage heart failure is associated with a down regulation of annexin VI and up regulation of annexin II and V proteins. Coordinate changes were observed in steady-state mRNA levels. These results suggest that these annexin isoforms may contribute to the regulation of intracellular Ca2+ homeostasis in the cardiomyopathic heart.     

Effect of troglitazone (Rezulin) on fructose 2,6-bisphosphate concentration and glucose metabolism in isolated rat hepatocytes

The effect of troglitazone, an orally effective thiazolidinedione, on lactate- and glucagon-stimulated gluconeogenesis (in the absence of insulin) was examined in hepatocytes isolated from rats under different nutritional states. Hepatocytes obtained from fed or 20-24 hr fasted male Sprague-Dawley rats were incubated in Krebs-Henseleit Bicarbonate buffer (KHBC) (in presence or absence of 10.0 mM glucose) containing 2.0 mM [U-14C]lactate (0.1-0.25 microCi) with or without 10.0 nM glucagon and troglitazone (30.0 microM) or the appropriate vehicle. Aliquots were removed at specified endpoints and assayed for glucose and fructose 2,6-bisphosphate (F-2,6-P2) concentrations. In 20-24 hour starved hepatocytes, troglitazone produced a 26.1% inhibition of lactate-stimulated gluconeogenesis. This inhibitory effect of troglitazone on hepatic gluconeogenesis was further potentiated by incubation of the cells with glucose in vitro. In hepatocytes obtained from fasted rats (and incubated with 10 mM glucose in vitro) troglitazone reduced lactate-and glucagon-stimulated gluconeogenesis by 53% and 56%, respectively. This reduction in hepatic glucose production was associated with 1.06 and 1.04 fold increase in the hepatocyte F-2,6-P2 content. In isolated hepatocytes from fed animals and incubated with 10 mM glucose in vitro, troglitazone (15 and 30 microM) did not have any effect on either lactate- or glucagon-stimulated gluconeogenesis. However, 30 microM troglitazone significantly enhanced (36%) F-2,6-P2 concentrations during lactate-stimulated gluconeogenesis. These findings demonstrate that troglitazone decreases hepatic glucose production through alterations in the activity of one or more gluconeogenic/glycolytic enzymes, depending upon the nutritional state of the animal and the presence or absence of hormonal modulation. All of the effects of troglitazone in the present study were observed in the absence of insulin, suggesting an "insulinomimetic" effect. However, this does not exclude the possibility that troglitazone may also function as an "insulin sensitizer" in hepatic and certain other tissues.     

Reversible independent alterations in glucose transport and metabolism in cultured human cells deprived of glucose

During cell division in the Xenopus egg (diameter 1.25 mm) new cell membrane is formed in the furrow region (rate of growth approx 4-10(4) mum2/min). Freeze-fracture electron microscopy has produced the following data. Preexisting plasma membrane faces show a reversed polarity with respect to particle distribution, i.e. more particles are attached to the E-face (density 1600-2200 particles/mum2) than to the P-face (300 particles/mum2). A frequency histogram of 2331 measured intramembranous particles does not show a continuous range of sizes. The following sizes were very obvious: 95 A (12%), 125 A (30%) and 180 A (6%). At the tips of surface protrusions both the E- and the P- face are particle-free. Nascent cell membrane fracture faces are more difficult to obtain. The particle density is low (E-face 300-500 particles/mum2). Lowering the ambient temperature to 5 degrees C for approx. 5 mins does not change the normal particle pattern, but it improves the output in nascent membrane fracture faces. The fact that in the Xenopus egg preexisting and nascent membrane regions are continuous but nevertheless maintain their highly different particle densities is noteworthy. The freeze-fracture data are discussed in relation to, among other things, the known values of the specific resistances of these membrane regions.     

Effects of nonesterified fatty acids on glucose metabolism after glucose ingestion

Impaired suppression of plasma nonesterified fatty acids (NEFAs) after glucose ingestion may contribute to glucose intolerance, but the mechanisms are unclear. Evidence that insulin inhibits hepatic glucose output (HGO), in part by suppressing plasma NEFA levels, suggests that impaired suppression of plasma NEFA after glucose ingestion would impair HGO suppression and increase the systemic delivery of glucose. To test this hypothesis, we studied glucose kinetics (constant intravenous [3-3H]glucose [0.4 microCi/min], oral [1-14C]glucose [100 microCi]), whole-body substrate oxidation, and leg glucose uptake in eight normal subjects (age, 39 +/- 9 years [mean +/- SD]; BMI, 24 +/- 2 kg/m2) in response to 75 g oral glucose on two occasions. In one study, plasma NEFAs were prevented from falling by infusion of 20% Liposyn (45 ml/h) and heparin (750 U/h). Plasma glucose rose more rapidly during lipid infusion (P < 0.05), and mean levels tended to be higher after 120 min (6.45 +/- 0.41 vs. 5.81 +/- 0.25 SE, 0.1 < P < 0.05, NS); peak glucose levels were similar. Total glucose appearance (Ra) was higher during lipid infusion due to a higher HGO (28.4 +/- 1.0 vs. 21.2 +/- 1.5 g over 4 h, P < 0.005). Total glucose disposal (Rd) was also higher (88 +/- 2 vs. 81 +/- 3 g in 4 h, P < 0.05). Plasma insulin rose more rapidly after glucose ingestion with lipid infusion, and leg glucose uptake was 33% higher (P < 0.05) during the 1st hour. During lipid infusion, subjects oxidized less glucose (47 +/- 3 vs. 55 +/- 2 g, P < 0.05) and more fat (7.1 +/- 0.8 vs. 3.9 +/- 0.9 g, P < 0.02). In summary, 1) impaired suppression of NEFAs after oral glucose impairs insulin's ability to suppress HGO, and 2) in normal subjects the greater insulin response compensates for the increased systemic glucose delivery by increasing peripheral glucose Rd.     

Protein metabolism in human obesity: relationship with glucose and lipid metabolism and with visceral adipose tissue

It is controversial whether metabolic disorders of human obesity include protein metabolism. Even less information is available concerning the effect of fat distribution on protein metabolism. Therefore, a comprehensive evaluation of glucose, lipid, and protein metabolism was performed in 11 obese nondiabetic and 9 normal women whose body composition and regional fat distribution were determined. [1-14C]Leucine and [3-3H]glucose were infused in the postabsorptive state and during an euglycemic hyperinsulinemic (35-40 microU/mL) clamp combined with indirect calorimetry for assessment of leucine flux, oxidation, and nonoxidative disposal, glucose turnover and oxidation, and lipid oxidation. Fat-free mass (FFM) was estimated by a bolus of 3H2O. Subcutaneous abdominal and visceral adipose tissues were determined by nuclear magnetic resonance imaging. During the clamp, obese women had lower glucose turnover (4.51 +/- 0.41 vs. 6.63 +/- 0.40 mg/min.kg FFM; P < 0.05), with a defect in both oxidation (3.27 +/- 0.22 vs. 3.89 +/- 0.21) and nonoxidative disposal (1.24 +/- 0.27 vs. 2.74 +/- 0.41; P < 0.005), whereas lipid oxidation was higher during the clamp (0.49 +/- 0.15 vs. 0.17 +/- 0.09 mg/min.kg FFM). There was no difference in leucine flux (basal, 2.23 +/- 0.17 vs. 2.30 +/- 0.29; clamp, 2.06 +/- 0.19 vs. 2.10 +/- 0.24 mumol/min.kg FFM), oxidation (basal, 0.37 +/- 0.04 vs. 0.36 +/- 0.05; clamp, 0.34 +/- 0.04 vs. 0.39 +/- 0.06) and nonoxidative leucine disposal (basal, 1.86 +/- 0.17 vs. 1.94 +/- 0.26; clamp, 1.72 +/- 0.20 vs. 1.71 +/- 0.19) in the two groups. In obese women, basal leucine oxidation was directly related with glucose oxidation and inversely to lipid oxidation (both P < 0.05), whereas visceral adipose tissue was inversely related to leucine flux both in the basal state and during the clamp (P < 0.05). In conclusion, in human obesity, 1) rates of protein metabolism in the basal state and in the range of insulin concentrations encountered after a meal are normal; 2) protein oxidation is positively related to glucose oxidation and negatively related to lipid oxidation; and 3) visceral adipose tissue is inversely related to all parameters of protein metabolism.     

Effect of cilazapril therapy on glucose and lipid metabolism in patients with hypertension

The effects of long-term monotherapy with cilazapril, an angiotensin-converting enzyme inhibitor, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 66 patients with hypertension: 23 with normal glucose tolerance and 43 with glucose intolerance (including 9 patients with non-insulin-dependent diabetes mellitus). The levels of plasma glucose, serum insulin, serum lipids, glycated hemoglobin A(lc) (Hb A(lc)), and fructosamine were determined before and during long-term (mean +/- SD, 26.2 +/- 1.2 weeks) therapy with cilazapril. A 75-g oral glucose tolerance test was performed before and during treatment. Significant reductions in both systolic and diastolic blood pressures in both patient groups were maintained during the study. Neither fasting nor post-glucose load venous plasma glucose levels were altered in either group of patients, and no patient with normal glucose tolerance developed diabetes mellitus during the study. There was no significant change in the insulinogenic index (delta serum insulin/delta venous plasma glucose at 30 minutes post-glucose load) in either group, and glucose intolerance was slightly improved with significant reductions (P < 0.01) in Hb A(lc) and fructosamine in the patient group with impaired glucose tolerance. Serum total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride levels were significantly (P < 0.01) decreased and high-density lipoprotein cholesterol levels increased in patients with hypercholesterolemia (TC levels > or = 5.69 mmol/L). These results suggest that long-term cilazapril therapy may improve glucose and lipid metabolism in hypertensive patients with impaired glucose tolerance. Cilazapril also appears to be useful as an antihypertensive agent for hypertensive patients with either impaired glucose tolerance or hypercholesterolemia.     

Effects of metformin on glucose and glucagon regulated gluconeogenesis in cultured normal and diabetic hepatocytes

The effects of glucose and glucagon on the anti-gluconeogenic action of metformin were investigated in normal and diabetic hepatocytes. Glucose production from lactate was elevated by 88% in hepatocytes from fasted normal rats compared with hepatocytes from fed animals. Diabetes caused 3.5- and 2.1-fold increases in hepatic gluconeogenesis under fasting and fed conditions, respectively. Metformin (250 microM) suppressed glucose production by 37% in normal and by 30% in diabetic hepatocytes from fed rats. This drug was more effective (up to 67%) with increasing concentrations of glucose in the medium. Potentiation by metformin of insulin action on gluconeogenesis was elevated significantly (P < 0.01 to 0.001) by glucose in vitro. Metformin (75-250 microM) also counteracted the effects of glucagon at optimal concentrations in normal (32-68%) as well as diabetic (8-46%) hepatocytes. The findings of this study indicate that (i) the anti-gluconeogenic effect of metformin is enhanced by glucose in vivo and in vitro; and (ii) the suppression of glucagon-induced gluconeogenesis by metformin could play a role in its glucose-lowering effects in diabetic conditions.     

Effects of increased glucokinase gene copy number on glucose homeostasis and hepatic glucose metabolism

The relationship between glucokinase (GK) gene copy number and glucose homeostasis was studied in transgenic mice with additional copies of the entire GK gene locus (Niswender, K. D., Postic, C., Jetton, T. L., Bennett, B. D., Piston, D. W., Efrat, S., and Magnuson, M. A. (1997) J. Biol. Chem. 272, 22564-22569). The plasma glucose concentration was reduced by 25 +/- 3% and 37 +/- 4% in mice with one or two extra copies of the gene locus, respectively. The basis for the hypoglycemic phenotype was determined using metabolic tracer techniques in chronically cannulated, conscious mice with one extra GK gene copy. Under basal conditions (6-h fasted) transgenic mice had a lower blood glucose concentration (-12 +/- 1%) and a slightly higher glucose turnover rate (+8 +/- 3%), resulting in a significantly higher glucose clearance rate (+21 +/- 2%). Plasma insulin levels were not different, suggesting that increased glucose clearance was due to augmented hepatic, not islet, GK gene expression. Under hyperglycemic clamp conditions the transgenic mice had glucose turnover and clearance rates similar to the controls, but showed a lower plasma insulin response (-48 +/- 5%). Net hepatic glycogen synthesis was markedly elevated (+360%), whereas skeletal muscle glycogen synthesis was decreased (-40%). These results indicate that increased GK gene dosage leads to increased hepatic glucose metabolism and, consequently, a lower plasma glucose concentration. Increased insulin secretion was not observed, even though the transgene is expressed in islets, because hypoglycemia causes a down-regulation in islet GK content (Niswender, K. D., Postic, C., Jetton, T. L., Bennett, B. D., Piston, D. W., Efrat, S., and Magnuson, M. A. (1997) J. Biol. Chem. 272, in press).     

Modifications of glucose and lipid metabolism in cold-acclimated lean and genetically obese rats

Glucose turnover rate, 2-deoxy-D-[3H]glucose (2-DG) uptake, lipid synthesis in liver, white adipose tissue, and brown adipose tissue (BAT) were measured in lean FA/FA and genetically obese fa/fa rats either kept at 21 degrees C or acclimated to a cold environment (4 degrees C). After 10 days at 4 degrees C, lean rats increased their glucose turnover rate; 2-DG uptake as well as lipid synthesis in BAT were markedly stimulated. After cold acclimation, obese rats also increased glucose turnover; however, BAT glucose utilization was only slightly stimulated. Basal hyperinsulinemia and muscle insulin resistance of the obese group (as assessed by reduced 2-DG uptake in the soleus muscle) were present at room temperature and persisted at 4 degrees C. Total BAT lipid synthesis was increased to the same extent as in lean rats. Obese rat liver lipid synthesis, already much higher than normal at 21 degrees C, was further increased by cold exposure. We conclude that obese cold-acclimated fa/fa rats do not improve their muscle insulin resistance and barely improve BAT glucose utilization. We further suggest that an additional activation of hepatic lipid synthesis and oxidation thereof could participate in the heat production needed by the cold-acclimated obese rats.     

Gemfibrozil in the elderly. Effects on lipid metabolism

METHODS: Twenty patients with mixed hyperlipidemia type IIb were treated for two weeks with the lipid lowering agent gemfibrozil at a dose of 900 mg/day. The mean age of the 10 younger ambulatory patients was 32.3 +/- 4.1 years, that of the 10 geriatric inpatients 76.9 +/- 7.1 years. Fasting blood samples were drawn from the patients on days 1, 7 and 14, and plasma lipids and apolipoproteins determined. In addition, the plasma phospholipids were isolated and the fatty acid composition determined by gas chromatography. RESULTS: After only two weeks treatment with gemfibrozil, triglyceride and phospholipid plasma levels were significantly decreased. The therapeutic effects were more pronounced in the elderly patients, mainly female and most with diabetes mellitus, than in the younger, predominantly male hyperlipidemic patients. In accordance with the mechanism of action of gemfibrozil, the initially pathologically elevated levels of plasma free fatty acids in the geriatrics returned to normal. Furthermore, the fraction of long chain saturated fatty acids among the phospholipids became smaller, suggesting an impairment of chain elongation of fatty acids in the hepatic microsomes.     

Effects of tennis training on lipid metabolism and lipoproteins in recreational players

OBJECTIVE: Metabolic and ergogenic effects of carbohydrate and caffeine concentrations, common in commercial available beverages, were investigated in 16 tournament players (8 males and 8 females) during a 4 hrs interrupted tennis match (30 min rest after 150 min). METHODS: On three double-blind occasions players ingested a placebo (PLA), carbohydrate (CHO) or caffeine drink (CAF) at court changeover and during the resting period. In men (women) total intake consisted of 2.8 l (2.0 l) fluid, supplemented with 243 g (182 g) carbohydrates (CHO) or with 364 mg (260 mg) caffeine (CAF), respectively. Postexercise all players performed a ball-machine test (BMT) and a tennis-sprint test (TST). RESULTS: During match play blood glucose (GLU) was higher in CHO and did not differ between CAF and PLA. Immediately after the resting period GLU temporary declined in CHO and PLA, while no significant changes occurred in CAF. Increases of serum FFA and glycerol as well as the decrease of insulin were similar during the PLA and CAF trials and less pronounced in CHO. Postexercise urine concentrations of epinephrine and caffeine were significantly higher in CAF. Perception ratings and hitting accuracy (BMT) were not affected by treatment. CHO resulted in higher blood lactate levels during match play and a better post-exercise sprint performance (TST). Under CAF women won significantly more games than during both other treatments. CONCLUSIONS: CHO enhances tennis-specific running-speed but has no ergogenic effect on tennis performance under the conditions of our study. CAF improves glucose homeostasis at the beginning of work load after rest and may increase tennis success in women.     

Effects of epinephrine on glucose metabolism in patients with alcoholic cirrhosis

The cirrhotic liver has been shown to be resistant to the actions of various glucoregulatory hormones. The objective of this study was to investigate the effects of epinephrine on hepatic glucose metabolism in cirrhotic patients. Thirteen cirrhotic and eight healthy subjects were studied. Hepatic glucose production and turnover of alanine and glycerol were measured using stable isotope technique before and during 70 and 150 minutes of epinephrine infusion (0.1 microgram/kg/min). beta-Adrenoreceptor binding sites and affinity in mononuclear leukocyte membranes also were determined. Hepatic glucose production and alanine turnover in normals significantly increased during epinephrine infusion, but did not change in cirrhotics. Glycerol turnover increased after 70 minutes of epinephrine infusion in both groups. Epinephrine induced a significant rise of high-affinity beta-adrenoreceptor binding sites in normals, yielding a significant correlation between hepatic glucose production and receptor density (r = .94, P < .0001). In cirrhotic patients, similar changes in the number of high-affinity beta-adrenoreceptors were observed, but no correlation with hepatic glucose production was detected. The cirrhotic liver did not respond normally to the stimulatory effect of epinephrine on hepatic glucose production. Because this blunted response was not related to changes of beta-adrenoreceptors, our findings suggest that epinephrine resistance in cirrhosis was caused by a postreceptor defect.     

过量维生素E摄入对大鼠脂代谢的影响

目的:探讨摄入大剂量维生素E(VE)对大鼠脂代谢的影响,为VE摄入限量值的确定提供实验依据.方法:28只成年健康雌性Wistar大鼠随机分为正常对照组、低剂量VE组(400 mg·kg-1)、中剂量VE组(800 mg·kg-1)和高剂量VE组(1600 mg·kg-1),每天定时采用灌胃方法给予VE,定期根据体质量调整剂量,给药16 d后,经眼球采血,检测血清中总胆固醇(TC)、甘油三酯(TG)和高密度脂蛋白(HDL-C)等生化指标;处死大鼠取肝、肾、脾,计算上述脏器的脏体比.结果:与正常对照组比较,低、中和高剂量VE组大鼠饮水、进食量减少,状态及活动欠佳;与正常对照组和低剂量VE组比较,中、高剂量VE组大鼠体质量降低(P<0.05);与正常对照组比较,VE各剂量组大鼠肝/体比、肾/体比和脾/体比差异无统计学意义(P>0.05).与正常对照组比较,中、高剂量VE组大鼠血清中TC、TG和HDL-C水平均显著降低(P<0.05);与低剂量VE组比较,中、高剂量VE组TC、TG和HDL-C水平均显著降低(P<0.05);中、高剂量VE组之间比较差异无统计学意义(P>0.05).结论:大剂量VE抑制大鼠的生长,过量口服会降低体内HDL-C、TC和TG的合成,不利于脂代谢,提示不建议大量补充VE.     

Effects of oral clonidine premedication on plasma glucose and lipid homeostasis associated with exogenous glucose infusion in children

BACKGROUND: Oral clonidine may influence plasma glucose and lipid homeostasis by modulating endocrinologic responses to surgical stress. The effect of oral clonidine premedication on plasma glucose and lipid homeostasis associated with exogenous glucose infusion were investigated in children undergoing minor surgery. METHODS: Otherwise healthy children (n, 120; aged 3-13 yr) were assigned randomly to six groups according to the glucose concentration of the intravenous solution (0%, 2%, or 5%, at a rate of 6 ml kg(-1) x h(-1)) and the preoperative medications (4 microg/kg clonidine or placebo given 100 min before anesthesia) they were to receive. The plasma concentrations of glucose, nonesterified fatty acid, ketone bodies, epinephrine, norepinephrine, and cortisol were determined. RESULTS: Infusion of 5% glucose caused hyperglycemia (mean glucose concentration >200 mg/dl) in six children receiving placebo and two receiving clonidine. Although the mean plasma glucose concentration increased in three placebo groups, it was unchanged and the plasma concentrations of total ketone bodies and nonesterified fatty acid were increased in children receiving clonidine and glucose-free solution. The plasma epinephrine, norepinephrine, and cortisol levels in children receiving placebo increased in response to surgery. Clonidine attenuated the increase in catecholamines and cortisol. CONCLUSIONS: Oral clonidine premedication attenuated the hyperglycemic response, probably by inhibiting the surgical stress-induced release of catecholamines and cortisol. Infusion of 2% of glucose maintained plasma glucose concentrations within physiologic ranges in children receiving clonidine.     

Protein: metabolism and effect on blood glucose levels

Insulin is required for carbohydrate, fat, and protein to be metabolized. With respect to carbohydrate from a clinical standpoint, the major determinate of the glycemic response is the total amount of carbohydrate ingested rather than the source of the carbohydrate. This fact is the basic principle of carbohydrate counting for meal planning. Fat has little, if any, effect on blood glucose levels, although a high fat intake does appear to contribute to insulin resistance. Protein has a minimal effect on blood glucose levels with adequate insulin. However, with insulin deficiency, gluconeogenesis proceeds rapidly and contributes to an elevated blood glucose level. With adequate insulin, the blood glucose response in persons with diabetes would be expected to be similar to the blood glucose response in persons without diabetes. The reason why protein does not increase blood glucose levels is unclear. Several possibilities might explain the response: a slow conversion of protein to glucose, less protein being converted to glucose and released than previously thought, glucose from protein being incorporated into hepatic glycogen stores but not increasing the rate of hepatic glucose release, or because the process of gluconeogenesis from protein occurs over a period of hours and glucose can be disposed of if presented for utilization slowly and evenly over a long time period.     

Effects of infused sodium lactate on glucose and energy metabolism in healthy humans

To assess the effects of lactate on glucose metabolism, sodium lactate (20 mumol.kg-1.min-1) was infused into healthy subjects in basal conditions and during application of a hyperinsulinaemic (6 pmol.kg-1.min-1) euglycaemic clamp. Glucose rate of appearance (GRa) and disappearance (GRd) were measured from plasma dilution of infused U- 13C glucose, and glucose oxidation (G(ox)) from breath 13CO2 and plasma 13C glucose. In basal conditions, lactate infusion did not alter G(ox) (8.8 +/- 0.9 vs 9.2 +/- 1.1 mumol.kg-1.min-1), while GRa slightly decreased from 15.2 +/- 0.8 basal to 13.9 +/- 0.9 mumol.kg-1.min-1 after lactate (p < 0.05). During a hyperinsulinaemic clamp, hepatic glucose production was completely suppressed with or without lactate. Lactate decreased G(ox) from 17.1 +/- 0.4 to 13.4 +/- 1.2 mumol.kg-1.min-1 (p < 0.05), whereas GRd was unchanged (39.7 +/- 3.6 vs 45.6 +/- 2.6 mumol.kg-1.min-1. It is concluded that infusion of lactate in basal conditions does not increase GRa or interfere with peripheral glucose oxidation, and that during hyperinsulinaemia lactate decreases glucose oxidation but does not alter hepatic or peripheral insulin sensitivity.