Summary
This study was undertaken to ascertain whether enhanced oxidation of intracellular lipids could explain the impaired carbohydrate metabolism of diabetes. Pieces of diaphragms removed from diabetic (60–75 mg/kg streptozotocin i.v.) and control rats were incubated for 1 h with palmitate-1-14C. Tissue lipids from one piece were separated on silicic acid columns and the amount and specific activity of free fatty acids (FFA), triglycerides (TG) and phospholipids (PL) were measured.14CO2 production was also assessed in some experiments. The other pieces of tissue were incubated for a subsequent hour (without radioactivity) at which time measurements of tissue lipid content and specific activity and14CO2 production were again performed. FFA incorporation into CO2, tissue TG and PL was normal. TG content was moderately and PL content was slightly reduced in diabetic tissue. Changes in diaphragm TG and PL content and specific activity during the 2nd h of incubation strongly suggested that most of the14CO2 produced during this period was derived from TG. Approximately 25% of tissue TG in both control and diabetic muscle was oxidized to CO2 during the 2nd h of incubation. In diaphragms from diabetic rats, (+)-octanoylcarnitine (an inhibitor of FFA oxidation) decreased TG oxidation considerably but had no effect on the impaired glucose uptake. Thus, these data do not support the hypothesis that the glucose-fatty acid cycle (utilizing either extra- or intracellular lipids) may account for the altered carbohydrate metabolism of diabetic muscle.
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Balasse E. O.: Effect of free fatty acids and ketone bodies on glucose uptake and oxidation in the dog — Hormone metab. Res.3, 403, 1971.
Beringer A., Bänder A., Glaninger J., Mayrhofer E., Schnack H.: Attempts towards oral diabetes therapy by means of inhibition of lipolysis with 5-methylpyrazole-3-carbonic acid — Hormone metab. Res.2, 81, 1970.
Bierman E. L., Dole V. P., Roberts T. N.: An abnormality of nonesterified fatty acid metabolism in diabetes mellitus — Diabetes6, 475, 1957.
Björntorp P., Hood B.: Studies on adipose tissue from obese patients with or without diabetes mellitus. I. Release of glycerol and free fatty acids — Acta med. scand.179, 221, 1966.
Bragdon J. H., Gordon R. S. Jr.: Tissue distribution of C14 after the intravenous injection of labeled chylomicrons and unesterified fatty acids in the rat — J. clin. Invest.37, 574, 1958.
Bray G. A., Davidson M. B., Drenick E. J.: Obesity: a serious symptom — Ann. intern. Med.77, 779, 1972.
Brozek J., Grande F.: Body composition and basal metabolism in man: correlation analysis versus physiological approach — Hum. Biol.27, 22, 1955.
Csorba T. R., Matsuda I., Kalant N.: Effects of insulin and diabetes on flux rates of plasma glucose and free fatty acids — Metabolism15, 262, 1966.
Davidson M. B.: Studies on the mechanism of pentobarbital-induced glucose intolerance — Hormone metab. Res.3, 243, 1971.
Davidson M. B.: Primary insulin antagonism of glucose transport in muscle from older-obese rat — Metabolism27 (Suppl. 2), 1994, 1978.
Davidson M. B.: Studies on the oxidation of muscle triglycerides — (Submitted for publication).
Davidson M. B.: Effect of growth hormone administration to hypophysectomized rats on muscle lipid metabolism — Metabolism (in press).
Davidson M. B., Bernstein J. M.: The effect of nicotinic acid on growth hormone-induced lipolysis and glucose intolerance — J. Lab. clin. Med.81, 568, 1973.
Davidson M. B., Goodner C. J.: Assay of insulin antagonism by serial incubation of paired rat hemidiaphragms — Diabetes15, 380, 1966.
Denton R. M., Randle P. J.: Hormonal control of lipid concentration in rat heart and gastrocnemius — Nature (Lond.)208, 488, 1965.
Dole V. P.: Relation between non-esterified fatty acids in plasma and metabolism of glucose — J. clin. Invest.35, 150, 1956.
Felber J. P., Vannotti A.: Effects of fat infusion on glucose tolerance and insulin plasma levels — Med. exp. (Basel)10, 153, 1964.
Fritz I. B., Kaplan E.: Effects of glucose on palmitate esterification by isolated rat diaphragms — Amer. J. Physiol.200, 1047, 1961.
Garland P. B., Randle P. J.: Regulation of glucose uptake by muscle. 10. Effects of alloxandiabetes, starvation, hypophysectomy and adrenalectomy, and of fatty acids, ketone bodies and pyruvate, on the glycerol output and concentrations of free fatty acids, long-chain fatty acyl-coenzyme A, glycerol phosphate and citrate-cycle intermediates in rat heart and diaphragm muscles — Biochem. J.93, 678, 1964.
Gilbert C. H., Kaye J., Galton D. J.: The effect of a glucose load on plasma fatty acids and lipolysis in adipose tissue of obese diabetic and nondiabetic patients — Diabetologia10, 135, 1974.
Ginsberg H., Kimmerling G., Olefsky J. M., Reaven G. M.: Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia — J. clin. Invest.55, 454, 1975.
Gomez F., Jequier E., Chabot V., Buber V., Felber J.-P.: Carbohydrate and lipid oxidation in normal human subjects: its influence on glucose tolerance and insulin response to glucose — Metabolism21, 381, 1972.
Havel R. J., Naimark A., Brochgrevink C. F.: Turnover rate and oxidation of free fatty acids of blood plasma in man during exercise: studies during continuous infusion of palmitate-1-C14 — J. clin. Invest.42, 1054, 1963.
Hoffman W. S.: A rapid photoelectric method for the determination of glucose in blood and urine — J. biol. Chem.120, 51, 1937.
Hollobaugh S. L., Tzagournis M., Folk R. L., Kruger F. A., Hamwi G. J.: The diabetogenic action of human growth hormone: glucose-fatty acid interrelationships — Metabolism17, 485, 1968.
Issekutz B. Jr., Miller H. I., Paul P., Rodahl K.: Source of fat oxidation in exercising dogs — Amer. J. Physiol.207, 583, 1964.
Jackson R. A., Peters N., Advani U., Perry G., Rogers J., Brough W. H., Pilkington T. R. E.: Forearm glucose uptake during the oral glucose tolerance test in normal subjects — Diabetes22, 442, 1973.
Lassers B. W., Wahlqvist M. L., Kaijser L., Carlson L. A.: Relationship in man between plasma free fatty acids and myocardial metabolism of carbohydrate substrates — Lancet2, 448, 1971.
Lowry O. H., Rosenbrough N. J., Farr A. L., Randall R. J.: Protein measurements with the Folin phenol reagent — J. biol. Chem.193, 265, 1951.
Magyar I., Lehoczky D., Marton I.: Sugar consumptionin vitro of the muscle tissue of diabetic patients — Diabetes14, 716, 1965.
Masoro E. J.: Skeletal muscle lipids. III. Analysis of the functioning of skeletal muscle lipids during fasting — J. biol. Chem.242, 1111, 1967.
McGarry J. D., Foster D. W.: Studies with (+)-octanoylcarnitine in experimental diabetic ketoacidosis — Diabetes23, 485, 1974.
Moody A. J., Jeffcoate S. L., Volund A.: The effects of anti-insulin serum on the disposal of an oral load of (6-14C) glucose by the tissues of the rat — Hormone metab. Res.4, 193, 1970.
Munkner C.: Fasting concentrations of non-esterified fatty acids in diabetic and non-diabetic plasma and diurnal variations in normal subjects — Scand. J. clin. Lab. Invest.11, 388, 1959.
Murthy V. K., Shipp J. C.: Accumulation of myocardial triglycerides in ketotic diabetes. Evidence for increased biosynthesis — Diabetes26, 222, 1977.
Neptune E. M. Jr., Sudduth H. C., Foreman D. R., Fash F. J.: Phospholipid and triglyceride metabolism of exercised rat diaphragm and the role of these lipids in fatty acid uptake and oxidation — J. Lipid Res.1, 229, 1960.
Nestel P. J., Carroll K. F., Silverstein M. D.: Influence of free fatty acid metabolism on glucose tolerance — Lancet2, 115, 1964.
Östman J.: Studiesin vitro on fatty acid metabolism of human subcutaneous adipose tissue in diabetes mellitus — Acta med. scand.177, 639, 1965.
Paul P., Issekutz B. Jr., Miller H. I.: Interrelationship of free fatty acids and glucose metabolism in the dog — Amer. J. Physiol.211, 1313, 1966.
Raben M. S., Hollenberg C. H.: Effect of growth hormone on plasma fatty acids — J. clin. Invest.38, 484, 1959.
Rabinowitz D.: Some endocrine and metabolic aspects of obesity — Ann. Rev. Med.21, 241, 1970.
Randle P. J., Garland P. B., Hales N. C., Newsholme E. A.: The glucose fatty acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus — Lancet1, 785, 1963.
Rizza R. A., Crass M. F., Shipp J. C.: Effect of insulin treatmentin vivo on heart glycerides and glycogen of alloxan-diabetic rats — Metabolism20, 539, 1971.
Schalch D. S., Kipnis D. M.: Abnormalities in carbohydrate tolerance associated with elevated plasma nonesterified fatty acids — J. clin. Invest.44, 2010, 1965.
Schonfeld G., Kipnis D. M.: Glucose-fatty acid interactions in the rat diaphragmin vivo — Diabetes17, 422, 1968.
Schonfeld G., Kipnis D. M.: Effect of fatty acid on carbohydrate and fatty acid metabolism of rat diaphragm — Amer. J. Physiol.215, 513, 1968.
Shen S.-W., Reaven G. M., Farquhar J. W.: Comparison of impedance to insulin-mediated glucose uptake in normal subjects and in subjects with latent diabetes — J. clin. Invest.49, 2151, 1970.
Soeldner J. S., Slone D.: Critical variables in the radioimmunoassay of serum insulin using the double antibody technic — Diabetes17, 771, 1965.
Spitzer J. J., Gold M.: Free fatty acid metabolism by skeletal muscle — Amer. J. Physiol.206, 159, 1964.
Stadie W. C., Haugaard N., Marsh J. B., Hills A. G.: The chemical combination of insulin with muscle (diaphragm) of normal rat — Amer. J. med. Sci.218, 265, 1949.
van Handel E.: Estimation of glycogen in small amounts of tissue — Analyt. Chem.11, 256, 1965.
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Davidson, M.B., Karjala, R.G. Lipid metabolism by muscle of diabetic rats. Acta diabet. lat 16, 95–104 (1979). https://doi.org/10.1007/BF02581088
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DOI: https://doi.org/10.1007/BF02581088