Regulation of glucose uptake by muscle. 8. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes and starvation, on the uptake and metabolic fate of glucose in rat heart and diaphragm muscles

Randle, P. J.; Newsholme, E. A.; Garland, P. B.

doi:10.1042/bj0930652

Cited by 685 publications

(397 citation statements)

References 25 publications

(15 reference statements)

Supporting

Mentioning

351

Contrasting

Unclassified

Order By: Relevance

“…Therefore, they could substitute for other substrates, like glucose, as energy sources. A sparing effect by free-fatty acids on insulin-induced glucose uptake has recently been demonstrated in vivo [3], thus confirming Randle's hypothesis of a glucose-sparing effect by a variety of substrates mainly linked to lipid metabolism [2]. A similar effect can be postulated for the insulin-mediated uptake of amino-acids.…”

Section: Discussionsupporting

confidence: 69%

“…Among them, plasma free fatty acid, ketone body and amino acid concentrations decrease markedly. Since competition between substrates as metabolic fuels may occur [2], glucose uptake in vivo could be indirectly enhanced by the concomitant decrease in concentration and utilization of other substrates. Therefore, "insulin sensitivity", measured with the euglycaemic, hyperinsulinaemic clamp technique, could be modified by preventing the fall and/or increasing the concentrations of the substrates suppressed by insulin.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Hyperaminoacidaemia reduces insulin-mediated glucose disposal in healthy man

et al. 1985

View full text Add to dashboard Cite

Summary.To determine whether hyperaminoacidaemia may modify insulin-mediated glucose disposal, normal subjects were studied with the euglycaemic glucose-clamp technique, with or without an amino acid infusion, at a rate sufficient to duplicate the plasma concentration of most amino acids. Steady-state glucose infusion rates to maintain euglycaemia were 36% lower during hyperaminoacidaemia (7.3 + 1.0 versus 11.4 _+ 0.8 mg. kg-1. rain-2, p < 0.01) at comparable insulin concentrations (92 + 6 versus 93 + 7 mU/1 respectively). Thus, under conditions of hyperinsulinaemia, amino acids could compete with glucose as metabolic fuels.Key words: Hyperaminoacidaemia, euglycaemic hyperinsulinaemic clamp, glucose disposal.During an euglycaemic, hyperinsulinaemic clamp, insulin-sensitivity is often expressed as the glucose infusion rate necessary to maintain euglycaemia [1]. However, many other metabolic changes occur under hyperinsulinaemic conditions. Among them, plasma free fatty acid, ketone body and amino acid concentrations decrease markedly. Since competition between substrates as metabolic fuels may occur [2], glucose uptake in vivo could be indirectly enhanced by the concomitant decrease in concentration and utilization of other substrates. Therefore, "insulin sensitivity", measured with the euglycaemic, hyperinsulinaemic clamp technique, could be modified by preventing the fall and/or increasing the concentrations of the substrates suppressed by insulin.Recently, increased plasma free fatty acid concentrations have been shown to reduce insulin-mediated glucose disposal [3]. However, it is not known whether in vivo increments in plasma amino acid concentrations may also affect glucose disposal rates. Therefore, the aim of the present study was to evaluate the effect ofhyperaminoacidaemia on insulin-mediated glucose utilization in postabsorptive normal subjects. Subjects and methodsHealthy subjects (aged 21-57 years) were studied in the post-absorptive state. All subjects had normal body weight, and consumed their usual weight-maintaining diet ( -30 kcal/kg per day, containing 50% of total calories as carbohydrates, 20% as protein and 30% as fat) for at least 3 days prior to the study. The details and the potential risks of the study were explained, and each subject signed an informed written consent before the initiation of the study. The subjects were divided into two groups. In group A, (five males, one female, age: 28 + 3 years, body mass index: 22.9+0.8), an euglycaemic-hyperinsulinaemic clamp was performed for 180 rain, as previously described [4]. Insulin was infused by means of a Harvard Pump (Harvard Apparatus, Millis, MA, USA), at the rate of 0.05 U.m 2-' .min -1. Blood glucose concentration was maintained by means of the Biostator (Miles Laboratories, Elkhart, IN, USA) [4] at 4.72 + 0.11 mmol/1 (coefficient of variation: ~11%). In group B (four males, one female, age: 35 + 5 years, body mass index: 22.0 + 0.7) the subjects were studied as for group A, with the addition of an amino acid infusion for the sam...

show abstract

Section: Discussionsupporting

confidence: 69%

mentioning

confidence: 99%

Hyperaminoacidaemia reduces insulin-mediated glucose disposal in healthy man

et al. 1985

View full text Add to dashboard Cite

show abstract

“…Furthermore, this suggestion could be correlated with the shift from glucose to fatty acids as the main source of energy. This is in agreement with the opinion that in diabetic muscle a decreased glucose uptake due to the increased concentration of fatty acids takes place [19]. It is also in agreement with the proposition that alterations in the intermediary metabolism of glucose and fatty acids in the skeletal muscle could serve as an explanation for the marked lethargy of O-H mice [3,4].…”

Section: Discussionsupporting

confidence: 91%

Lactate dehydrogenase activity and isoenzyme patterns in skeletal muscle, fat, exocrine pancreas and isolated pancreatic islets of normal and obese-hyperglycaemic mice

1970

View full text Add to dashboard Cite

Summary. The total lactate dehydrogenase (LDtt) activity and LDH isoenzyme patterns of isolated pancreatic islets, acinar pancreas, fat tissue and skeletal muscle from mice with obese-hyperglycaemic syndrome were compared with those of corresponding tissues from lean littermates. --The pancreatic tissues of obesehyperglyeaemic animals exhibited higher LDH activity than corresponding tissues of normal animals. This increase in LDH activity was not parallel in islets and acinar tissue. --No significant difference in the LDIt activity of either skeletal muscle or fat tissue between the two groups of animals was found. --In animals with obese-hyperglycaemic syndrome, LDI-I isoenzyme patterns of pancreatic islets, aeinar pancreas and fat showed LDI-I 5 increase and LDH 4 decrease. LDH isoenzyme patterns of skeletal muscle showed the decrease of LDH 5 percentage. --The LDH 1, LDtt 2 and LDtI 3 percentages of the fat tissue were lower in animals with obese-hyperglyeaemie syndrome, but those of the skeletal muscle were lower in normal animals. --Results presented are consistent with the opinion that in obese-hyperglycaemie mice both endocrine and exocrine pancreatic tissues as well as fat tend to have an increase in the proportion of glycolysis in their intermediary metabolism, whereas the reverse tendency --towards an increase in the proportion of oxidative pathways --is valid for skeletal muscle. Activitg de la lactate dgshydroggnase et r@artition des iaoenzymes dana le muscle atrid, le tissu adipeux, le pancreas exocrine et lea ~lota paner~atiques isolda de souris normales et ob~se-hyperglycdmiquesRdsumd. L'activit6 de la lactate d@shydrog@nase totale (LDH) et la r@artition des isoenzymes de la LDtt dans les riots pancr6atiques isol~s, le pancrdas aeineux, le tissu adipeux et le muscle strid de souris ayant un syndrome ob~se-hyperglyc@mique, ont dr@ compar6es avee celles des tissus correspondants de souris non-ob~ses de re@rues parents. --Les tissus pancr6atiques des animaux ob@se-hyperglycdmiques montraient une activitd LDtt plus dlevde que les tissus correspondants des animaux normaux. Cette augmentation de l'activit6 de la LDH n'dtait pas parall~le dans les riots et le tissu acineux. --On n'a trouv6 aueune diff@renee significative dans l'activitd de la LDtt du muscle strid ou du tissu adipeux entre les deux groupes d'animaux. --Chez les animaux ayant un syndrome ob~se-hyperglyc@mique, la r@artition des isoenzymes de la LDI-I dans les riots pancrdatiques, le pancrdas acineux et le tissu adipeux, montrait une augmentation de la LDH 5 et une diminution de la LDH 4. La r@artition des isoenzymes de la LDtt du muscle strid montrait une diminution du pourcentage de la LDH 5. --Les pourcenrages de LDH 1, de LDH 2 et de LDH 3 du tissu adipeux dtaient plus bas chez les animaux ayant un syndrome obgse-hyperglyc@mique, mais eeux du musele stri6 @talent plus bas chez les animaux normaux. --Les r@sultats pr6sent6s sont en concordance avec l'opinion que chez les souris obgse-hyperglycgmiques, ~ la fois les tissus pancr6atiques e...

show abstract

“…Inside the myocytes, the increased concentrations of fatty acids will impair myocardial function through increased ␤-oxidation and decreased glucose oxidation, as initially demon- strated by Randle et al (31) and confirmed by Lopaschuk et al (17). Recently, it has been shown that increased myocardial ␤-oxidation induced by high FFA and TG concentrations decreased heart glucose oxidation and myocardial recovery after acute myocardial ischemia (18,21).…”

Section: Effects Of Type 2 Diabetes Mellitus On Myocardial Insulin Rementioning

confidence: 86%

Myocardial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in Type 2 diabetic patients

Monti¹,

Landoni²,

Setola³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

dial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in Type 2 diabetic patients. Am J Physiol Heart Circ Physiol 287: H1225-H1231, 2004. First published May 6, 2004; 10.1152/ajpheart.00629.2003.-We evaluated the influence of chronic hypertriglyceridemia and endothelial dysfunction on myocardial glucose uptake (MGU) in Type 2 diabetic patients without coronary heart disease. Patients were divided into two groups according to fasting triglyceride (TG) levels: 5.4 Ϯ 1.1 and 1.5 Ϯ 0.3 mmol/l for high-and normal-TG groups, respectively. Five subjects were assigned to the high-TG group and 11 to the normal-TG group. Age, gender, body mass index, systolic and diastolic blood pressure, glucose, insulin, HbA1c, cholesterol, and HDL cholesterol were similar in the two groups, whereas free fatty acid (FFA) levels were higher in the high-TG group basally and at the end of the clamp. Furthermore, five healthy subjects were subjected to the same protocol and used as the control group. MGU was assessed by using 18 F-labeled 2-fluoro-2-deoxy-D-glucose under hyperglycemic-hyperinsulinemic conditions. Basal endothelin-1 and nitric oxide levels were significantly higher in the high-TG group than in the normal-TG and control groups, and cGMP and maximal postischemic vasodilation were significantly decreased in the high-TG group compared with the normal-TG and control groups. However, significant alterations were found in the same parameters in the normal-TG group compared with the control group. By the end of the hyperglycemic clamp, in the high-TG group, MGU was ϳ40 and 65% of that in the normal-TG and control groups. MGU negatively correlated with TG, FFA, and endothelin-1, whereas a positive correlation was found with cGMP and maximal postischemic vasodilation. In conclusion, increased TG and FFA levels are risks, in addition to Type 2 diabetes mellitus, for myocardial insulin resistance, endothelial dysfunction, and alteration of nitric oxide/cGMP levels. triglycerides; myocardial glucose uptake; positron emission tomography study; endothelium; free fatty acid FOR MANY YEARS, hypertriglyceridemia was considered a marker of cardiovascular disease only in certain subjects, such as women (5, 12) and patients with Type 2 diabetes (10). The association between triglycerides (TGs), independently of HDL cholesterol levels, and definite cardiovascular disease, such as myocardial infarction or angina, was found in some studies (5) and denied in others, in which the simultaneous association of high TG and low HDL cholesterol was necessary to predict cardiovascular risk (8). This apparent discrepancy is probably related to the fact that it is quite difficult to match for duration and degree of cardiovascular disease in different populations, and, when cardiovascular disease is established, some factors might have lost their primary pathogenic significance. Hypertriglyceridemia occurs frequently in patients with coronary heart disease (CHD) and in survivors of myocardial infarction (5), and, durin...

show abstract

Regulation of glucose uptake by muscle. 8. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes and starvation, on the uptake and metabolic fate of glucose in rat heart and diaphragm muscles

Cited by 685 publications

References 25 publications

Hyperaminoacidaemia reduces insulin-mediated glucose disposal in healthy man

Hyperaminoacidaemia reduces insulin-mediated glucose disposal in healthy man

Lactate dehydrogenase activity and isoenzyme patterns in skeletal muscle, fat, exocrine pancreas and isolated pancreatic islets of normal and obese-hyperglycaemic mice

Myocardial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in Type 2 diabetic patients

Contact Info

Product

Resources

About