Glucose-fatty acid cycle to inhibit glucose utilization and oxidation is not operative in fatty acid-cultured islets

Diabetes ◽  
1999 ◽  
Vol 48 (9) ◽  
pp. 1747-1753 ◽  
Author(s):  
Y. Q. Liu ◽  
K. Tornheim ◽  
J. L. Leahy
Keyword(s):  
Fatty Acid ◽  
Glucose Utilization ◽  
Acid Cycle ◽  
Glucose Fatty Acid Cycle

The glucose–fatty acid cycle: a physiological perspective

2003 ◽  
Vol 31 (6) ◽  
pp. 1115-1119 ◽  
Author(s):  
K.N. Frayn
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Glucose Utilization ◽  
Acid Oxidation ◽  
Acid Cycle ◽  
Glucose Fatty Acid Cycle ◽  
High Concentrations ◽  
Glucose Stimulated Insulin Secretion ◽  
Glucose Output ◽  
Carnitine Palmitoyltransferase 1

Glucose and fatty acids are the major fuels for mammalian metabolism and it is clearly essential that mechanisms exist for mutual co-ordination of their utilization. The glucose–fatty acid cycle, as it was proposed in 1963, describes one set of mechanisms by which carbohydrate and fat metabolism interact. Since that time, the importance of the glucose–fatty acid cycle has been confirmed repeatedly, in particular by elevation of plasma non-esterified fatty acid concentrations and demonstration of an impairment of glucose utilization. Since 1963 further means have been elucidated by which glucose and fatty acids interact. These include stimulation of hepatic glucose output by fatty acids, potentiation of glucose-stimulated insulin secretion by fatty acids, and the cellular mechanism whereby high glucose and insulin concentrations inhibit fatty acid oxidation via malonyl-CoA regulation of carnitine palmitoyltransferase-1. The last of these mechanisms, discovered by Denis McGarry and Daniel Foster in 1977, provides an almost exact complement to the mechanism described in the glucose–fatty acid cycle whereby high concentrations of fatty acids inhibit glucose utilization. These additional discoveries have not detracted from the important of the glucose–fatty acid cycle: rather, they have reinforced the importance of mechanisms whereby glucose and fat can interact.

scholarly journals GH replacement causing acute hyperglycaemia and ketonuria in a type 1 diabetic patient

2013 ◽  
Vol 2013 ◽  
Author(s):  
Dominic Cavlan ◽  
Shanti Vijayaraghavan ◽  
Susan Gelding ◽  
William Drake
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Type 1 Diabetes ◽  
Fatty Acid ◽  
Diabetic Patient ◽  
Acid Cycle ◽  
Gh Replacement ◽  
Glucose Fatty Acid Cycle ◽  
Gh Excess

Summary A state of insulin resistance is common to the clinical conditions of both chronic growth hormone (GH) deficiency and GH excess (acromegaly). GH has a physiological role in glucose metabolism in the acute settings of fast and exercise and is the only anabolic hormone secreted in the fasting state. We report the case of a patient in whom knowledge of this aspect of GH physiology was vital to her care. A woman with well-controlled type 1 diabetes mellitus who developed hypopituitarism following the birth of her first child required GH replacement therapy. Hours after the first dose, she developed a rapid metabolic deterioration and awoke with hyperglycaemia and ketonuria. She adjusted her insulin dose accordingly, but the pattern was repeated with each subsequent increase in her dose. Acute GH-induced lipolysis results in an abundance of free fatty acids (FFA); these directly inhibit glucose uptake into muscle, and this can lead to hyperglycaemia. This glucose–fatty acid cycle was first described by Randle et al. in 1963; it is a nutrient-mediated fine control that allows oxidative muscle to switch between glucose and fatty acids as fuel, depending on their availability. We describe the mechanism in detail. Learning points There is a complex interplay between GH and insulin resistance: chronically, both GH excess and deficiency lead to insulin resistance, but there is also an acute mechanism that is less well appreciated by clinicians. GH activates hormone-sensitive lipase to release FFA into the circulation; these may inhibit the uptake of glucose leading to hyperglycaemia and ketosis in the type 1 diabetic patient. The Randle cycle, or glucose–fatty acid cycle, outlines the mechanism for this acute relationship. Monitoring the adequacy of GH replacement in patients with type 1 diabetes is difficult, with IGF1 an unreliable marker.

Insulin sensitivity of rates of glycolysis and glycogen synthesis in soleus, stripped soleus, epitrochlearis, and hemi-diaphragm muscles isolated from sedentary rats

1983 ◽  
Vol 3 (7) ◽  
pp. 675-679 ◽  
Author(s):  
R. A. J. Challiss ◽  
J. Espinal ◽  
E. A. Newsholme
Keyword(s):  
Fatty Acid ◽  
Glucose Utilization ◽  
Glycogen Synthesis ◽  
Maximal Inhibition ◽  
Maximal Stimulation ◽  
Glucose Fatty Acid Cycle ◽  
Isolated Adipocytes ◽  
Stimulation Of

The effect of insulin concentrations on the rates of glycolysis and glycogen synthesis in four different in vitro rat muscle preparations (intact soleus, stripped soleus, epitrochlearis, and hemi-diaphragm) were investigated: the concentrations of insulin that produced half-maximal stimulation of the rates of these two processes in the four muscle preparations were similar – about 100 μunits/ml. This is at least 10-fold greater than the concentration that produced half-maximal inhibition of lipolysis in isolated adipocytes. Since 100 μunits/ml insulin is outside the normal physiological range in the rat, it is suggested that, in vivo, insulin influences glucose utilization in muscle mainly indirectly, via changes in the plasma fatty acid levels and the ‘glucose/fatty acid cycle’. Consequently the view that insulin stimulates glucose utilization in muscle mainly by a direct effect on membrane transport must be treated with caution.

scholarly journals THE GLUCOSE-FATTY ACID CYCLE

1981 ◽  
Vol 53 (2) ◽  
pp. 123-129 ◽  
Author(s):  
J.C. STANLEY
Keyword(s):  
Fatty Acid ◽  
Acid Cycle ◽  
Glucose Fatty Acid Cycle

Skeletal muscle pyruvate dehydrogenase activity during acetate infusion in humans

1995 ◽  
Vol 268 (5) ◽  
pp. E1007-E1017 ◽  
Author(s):  
C. T. Putman ◽  
L. L. Spriet ◽  
E. Hultman ◽  
D. J. Dyck ◽  
G. J. Heigenhauser
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Dehydrogenase Activity ◽  
Pyruvate Dehydrogenase ◽  
Acetate Metabolism ◽  
Acetyl Coa ◽  
Acid Cycle ◽  
Citrate Accumulation ◽  
Acetyl Group ◽  
Glucose Fatty Acid Cycle

Pyruvate dehydrogenase activity (PDHa), acetyl group, and citrate accumulation were examined in human skeletal muscle at rest and during cycling exercise while acetate was infused. Eight subjects received 400 mmol of sodium acetate (Ace) at a constant rate during 20 min of rest, 5 min of cycling at 40% maximal O2 uptake (VO2max) and 15 min of cycling at 80% VO2max. Two weeks later experiments were repeated while 400 mmol of sodium bicarbonate was infused in the control condition (CON). Ace infusion increased muscle acetyl-coenzyme A (acetyl-CoA), citrate, and acetylcarnitine. A decline in resting PDHa during 20 min of Ace infusion (0.37 +/- 0.08 vs. 0.16 +/- 0.03 mmol.min-1.kg wet wt-1) coincided with an elevation in the acetyl-CoA-to-free CoA ratio (acetyl-CoA/CoASH; 0.28 +/- 0.04 to 0.73 +/- 0.14). After 20 min of CON infusion, resting PDHa (0.32 +/- 0.06 mmol.min-1.kg wet wt-1) was similar to PDHa before Ace infusion. During exercise, acetyl-CoA, citrate, and acetyl-CoA/CoASH were further elevated, and the differences that existed at rest were resolved. PDHa increased to the same extent in Ace and CON, in which it was 44-47% transformed after 5 min at 40% VO2max and completely transformed after 15 min at 80% VO2max. At rest PDHa was regulated by variations in acetyl-CoA/CoASH secondary to enhanced acetate metabolism. Conversely, during exercise PDHa regulation appeared independent of variations in acetyl-CoA/CoASH. The resting data are consistent with a central role for PDHa and citrate in the regulation of the glucose-fatty acid cycle in skeletal muscle, as classically proposed. However, in the present study Ace infusion was not effective in perturbing the glucose-fatty acid cycle during exercise.

THE GLUCOSE FATTY ACID CYCLE IN OBESITY AND MATURITY ONSET DIABETES MELLITUS

1965 ◽  
Vol 131 (1 Adipose Tissu) ◽  
pp. 324-333 ◽  
Author(s):  
P. J. Randle ◽  
P. B. Garland ◽  
E. A. Newsholmet ◽  
C. N. Hales
Keyword(s):  
Diabetes Mellitus ◽  
Fatty Acid ◽  
Maturity Onset Diabetes ◽  
Acid Cycle ◽  
Onset Diabetes ◽  
Glucose Fatty Acid Cycle

scholarly journals Effects of starvation and exercise on concentrations of citrate, hexose phosphates and glycogen in skeletal muscle and heart. Evidence for selective operation of the glucose-fatty acid cycle

1985 ◽  
Vol 232 (2) ◽  
pp. 585-591 ◽  
Author(s):  
A Zorzano ◽  
T W Balon ◽  
L J Brady ◽  
P Rivera ◽  
L P Garetto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Ketone Bodies ◽  
Recovery Period ◽  
Moderate Intensity ◽  
Glycogen Depletion ◽  
Acid Cycle ◽  
Glucose Fatty Acid Cycle ◽  
Fructose 1,6 Bisphosphate ◽  
Hexose Phosphates

Concentrations of citrate, hexose phosphates and glycogen were measured in skeletal muscle and heart under conditions in which plasma non-esterified fatty acids and ketone bodies were physiologically increased. The aim was to determine under what conditions the glucose-fatty acid cycle might operative in skeletal muscle in vivo. In keeping with the findings of others, starvation increased the concentrations of glycogen, citrate and the fructose 6-phosphate/fructose 1,6-bisphosphate ratio in heart, indicating that the cycle was operative. In contrast, it decreased glycogen and had no effect on the concentration of citrate or the fructose 6-phosphate/fructose 1,6-bisphosphate ratio in the soleus, a slow-twitch red muscle in which the glucose-fatty acid cycle has been demonstrated in vitro. In fed rats, exercise of moderate intensity caused glycogen depletion in the soleus and red portion of gastrocnemius muscle, but not in heart. In starved rats the same exercise had no effect on the already diminished glycogen contents in skeletal muscle, but it decreased cardiac glycogen by 25-30%. After exercise, citrate and the fructose 6-phosphate/fructose 1,6-bisphosphate ratio were increased in the soleus of the starved rat. Significant changes were not observed in fed rats. The data suggest that in the resting state the glucose-fatty acid cycle operates in the heart, but not in the soleus muscle, of a starved rat. In contrast, the metabolite profile in the soleus was consistent with activation of the glucose-fatty acid cycle in the starved rat during the recovery period after exercise. Whether the cycle operates during exercise itself is unclear.

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