Studies on the Metabolism of Free Fatty Acids in Diabetic and Fasting Dogs*

Spitzer, John J.; Gold, Martin

doi:10.1111/j.1749-6632.1965.tb34792.x

Cited by 24 publications

(12 citation statements)

References 20 publications

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“…It should be noted, however, that if the (a -cs) concentration difference represents a net value, (combining cardiac release and uptake of FFA) the question of selectivity with regard to the extraction of individual FFA cannot be determined unless studied with several different labeled FFA. One cannot assume from the data obtained in this study that palmitate and total FFA fractional extractions are identical, but data from animal studies (42,43) and for exercising human skeletal muscle (13,44) indicate that this approach may lead to only small errors.…”

Section: Discussionmentioning

confidence: 86%

Free fatty acid metabolism of the human heart at rest

Most¹,

Brachfeld²,

Gorlin³

et al. 1969

J. Clin. Invest.

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A B S T R A C T Myocardial substrate metabolism was studied in 13 subjects at the time of diagnostic cardiac catheterization by means of palmitic acid-14C infusion with arterial and coronary sinus sampling. Two subjects were considered free of cardiac pathology and all, with one exception, demonstrated lactate extraction across the portion of heart under study. Data for this single lactate-producing subject were treated separately.The fractional extraction of '4C-labeled free fatty acids (FFA) (44.4+±9.5%) was nearly twice that of unlabeled FFA (23.2 ±7.8%) and raised the possibility of release of FFA into the coronary sinus. FFA uptake, based on either the arterial minus coronary sinus concentration difference or the FFA-14C fractional extraction, was directly proportional to the arterial FFA concentration. Gas-liquid chromatography failed to demonstrate selective handling of any individual FFA by the heart. Fractional oxidation of FFA was 53.5 ±+12.7%, accounting for 53.2 ±14.4% of the heart's oxygen consumption while nonlipid substrates accounted for an additional 30.0 ±17.3%. Determinations of both labeled and unlabeled triglycerides suggested utilization of this substrate by the fasting human heart. Direct measurement of FFA fractional oxidation as well as FFA uptake, exclusive of possible simultaneous FFA release, would appear necessary in studies concerned with human myocardial FFA metabolism.

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Section: Discussionmentioning

confidence: 86%

Free fatty acid metabolism of the human heart at rest

Most¹,

Brachfeld²,

Gorlin³

et al. 1969

J. Clin. Invest.

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“…I n the diabetic animals arterial acetoacetate levels were increased 50 fold (acute diabetic dogs) and 10 fold (chronic diabeth dogs), respectively ( Table I) [43] no correlation between AVDFFA and ArtFFA was found in the diabetic animals. The relevance of these results has been discussed in detail elsewhere [ 13,43,44].…”

Section: Lo-mentioning

confidence: 94%

“…Hence, any conclusions drawn from extracellular L/P values as to the state of the cytoplasmic redox potential do not seem to be justified under such conditions. [13,42,43]) and the extraction coefficient significantly reduced and negatively correlated to the arterial free fatty acids…”

Section: Pyruvate and Lactatementioning

confidence: 99%

Arterial Levels, Cardiac and Hepatic Arteriovenous Differences, Extraction Coefficients and Oxygen Extraction Ratios of Various Substrates in Normal, and in Acute and Chronic Alloxan‐Diabetic Dogs

Kraupp¹,

Adler-Kastner²,

Kolassa³

et al. 1968

European Journal of Biochemistry

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Arterial levels and cardiac and hepatic arteriovenous differences (AVD), extraction coefficients and oxygen extraction ratios of glucose, lactate, pyruvate, free fatty acids, acetoacetate, 3-hydroxybutyrate, citrate and oxygen were determined simultaneously by catheter techniques in anaesthetized (chloralose-urethane) normal, and in acute and chronic alloxandiabetic dogs. The differences in mean values between the normal and the diabetic groups were tested for their significance by analysis of variance and the dependence of AVD values on their corresponding arterial levels by correlation analysis. I.The arterial levels of glucose, free fatty acids, acetoacetate an2 3-hydroxybutyrate were significantly raised in both diabetic groups. Citrate was significantly elevated only in the acute diabetic animals. Arterial pyruvate was significantly lowered in both diabetic groups. Arterial pH values of around 7.24 were found in the acute diabetic animals.2. Cardiac AVD of glucose was significantly reversed in the acute diabetic dogs. The myocardial AVD of pyruvate and lactate were positive in normal, and significantly negative (except lactate in chronic diabetes) in both diabetic groups. A significant, positive correlation between myocardial AVD and arterial levels was obtained for lactate in the normal group and for pyruvate in normal and diabetic animals. Arterial lactate/pyruvate ratios were Significantly correlated to arterial lactate and pyruvate levels in the diabetic animals. Myocardial AVD and oxygen extraction ratio values of free fatty acids were not significantly changed in the diabetic groups, but myocardial free fatty acids extraction coefficient values were significantly reduced. The myocardial AVD and oxygen extraction ratio values of acetoacetate and 3-hydroxybutyrate were significantly increased in both diabetic groups. A positive correlation between AVD and the corresponding arterial levels of free fatty acids and acetoacetate was obtained in normal dogs. Myocardial citrate AVD and oxygen extraction ratio were significantly raised in the acute diabetic animals. 3.The hepatic AVD of glucose, lactate and pyruvate were negative (release) in normal animals. No significant change in hepatic glucose AVD was found in the diabetic animals, yet the hepatic AVD of lactate and pyruvate became significantly positive (uptake). A highly significant, positive correlation between hepatic AVD and the arterial level of pyruvate was obtained in normal and in diabetic animals, the regression line of the diabetic animals being shifted to a 10-fold lower range of arterial levels. The hepatic AVD of free fatty acids was significantly raised in the acute diabetic dogs and significantly correlated to the arterial free fatty acids level in normal and diabetic animals, with almost identical regression lines. The hepatic AVD of acetoacetate and 3-hydroxybutyrate were negative in all animals but significantly more negative in the diabetic groups. A positive, significant correlation was obtained between AVD and the arterial level of a...

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“…Total lipid oxidation was calculated from continuous indirect calorimetric measurements in the basal state and during the last 40 min of each insulin step as previously described (28 (30). Because palmitate has been shown to be representative of other long-chain fatty acids in healthy man (30,31) and in cirrhotic patients (13), the fractional turnover of palmitate can be assumed to be similar to that of total FFA. Therefore, labeled palmitate can be used to trace the total FFA fraction when studying whole-body FFA turnover.…”

Section: Analytical Determinationsmentioning

confidence: 99%

Effect of physiologic hyperinsulinemia on glucose and lipid metabolism in cirrhosis.

Petrides¹,

Groop²,

Riely³

et al. 1991

J. Clin. Invest.

140

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Insulin secretion and insulin sensitivity were evaluated in eight clinically stable cirrhotic patients and in 12 controls. OGTT was normal in cirrhotics but plasma insulin response was increased approximately twofold compared with controls. Subjects received a three-step (0.1, 0.5, 1.0 mU/kg -min) euglycemic insulin clamp with indirect calorimetry, 16-311J-glucose, and 11-"CJ-palmitate. During the two highest insulin infusion steps glucose uptake was impaired (333±031 vs. 5.06±0.40 mg/ kg. min, P < 0.01, and 6.09+0.50 vs. 7.95±0.52 mg/kg.m-, P < 0.01). Stimulation of glucose oxidation by insulin was normal; in contrast, nonoxidative glucose disposal (i.e., glycogen synthesis) was markedly reduced. Fasting (r = -0.553, P < 0.01) and glucose-stimulated (r = -0.592, P < 0.01) plasma insulin concentration correlated inversely with the severity of insulin resistance. Basal hepatic glucose production was normal in cirrhotics and suppressed normally with insulin. In postabsorptive state, plasma FFA conc (933±42 vs. 711±44 Mmol/ liter, P < 0.01) and FFA turnover (9.08±1.20 vs. 6. 03±0.53 ,umol/kg min, P < 0.01) were elevated in cirrhotics despite basal hyperinsulinemia; basal FFA oxidation was similar in cirrhotic and control subjects. With low-dose insulin infusion, plasma FFA oxidation and turnover failed to suppress normally in cirrhotics. During the two higher insulin infusion steps, all parameters of FFA metabolism suppressed normally. In summary, stable cirrhotic patients with normal glucose tolerance exhibit marked insulin resistance secondary to the impaired nonoxidative glucose disposal. Our results suggest that chronic hyperinsulinism may be responsible for the insulin resistance observed in cirrhosis. (J. Clin. Invest. 1991. 88:561-570.)

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Studies on the Metabolism of Free Fatty Acids in Diabetic and Fasting Dogs*

Cited by 24 publications

References 20 publications

Free fatty acid metabolism of the human heart at rest

Free fatty acid metabolism of the human heart at rest

Arterial Levels, Cardiac and Hepatic Arteriovenous Differences, Extraction Coefficients and Oxygen Extraction Ratios of Various Substrates in Normal, and in Acute and Chronic Alloxan‐Diabetic Dogs

Effect of physiologic hyperinsulinemia on glucose and lipid metabolism in cirrhosis.

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