Abstract
Ketonemia can be a physiological response to a reduction in dietary intake. It also may occur when energy demands exceed the energy intake. Normally, alimentary ketogenesis is the major source of ketone bodies in ruminants. During ketonemia there is increased hepatic ketone body production. During physiological ketosis, the mobilization of free fatty acids is inadequate to support a high rate of hepatic ketogenesis. However, during clinical ketosis, the hormonal status (low insulin, high glucagon/insulin ratio) in combination with hypoglycemia promotes excessive lipid mobilization and a greater hepatic removal of fatty acids and switches the liver to a higher rate of ketogenesis. The low insulin, furthermore, can impair maximal ketone body utilization, thus exacerbating the hyperketonemia.
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- ANNISON E. F., HILL K. J., LEWIS D. Studies on the portal blood of sheep. II. Absorption of volatile fatty acids from the rumen of the sheep. Biochem J. 1957 Aug;66(4):592–599. doi: 10.1042/bj0660592. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ANNISON E. F., WHITE R. R. Further studies on the entry rates of acetate and glucose in sheep, with special reference to endogenous production of acetate. Biochem J. 1962 Sep;84:546–552. doi: 10.1042/bj0840546. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BERGMAN E. N., KON K. ACETOACETATE TURNOVER AND OXIDATION RATES IN OVINE PREGNANCY KETOSIS. Am J Physiol. 1964 Feb;206:449–452. doi: 10.1152/ajplegacy.1964.206.2.449. [DOI] [PubMed] [Google Scholar]
- Baird G. D. Aspects of ruminant intermediary metabolism in relation to ketosis. Biochem Soc Trans. 1977;5(3):819–827. doi: 10.1042/bst0050819. [DOI] [PubMed] [Google Scholar]
- Balasse E. O., Havel R. J. Evidence for an effect of inulin on the peripheral utilization of ketone bodies in dogs. J Clin Invest. 1971 Apr;50(4):801–813. doi: 10.1172/JCI106551. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bassett J. M. The effects of glucagon on plasma concentrations of insulin, growth hormone, glucose, and free fatty acids in sheep: comparison with the effects of catecholamines. Aust J Biol Sci. 1971 Apr;24(2):311–320. doi: 10.1071/bi9710311. [DOI] [PubMed] [Google Scholar]
- Bassett J. M., Wallace A. L. Short-term effects of ovine growth hormone on plasma glucose, free fatty acids and ketones in sheep. Metabolism. 1966 Oct;15(10):933–944. doi: 10.1016/0026-0495(66)90164-8. [DOI] [PubMed] [Google Scholar]
- Bauman D. E. Intermediary metabolism of adipose tissue. Fed Proc. 1976 Sep;35(11):2308–2313. [PubMed] [Google Scholar]
- Bergman E. N. Hyperketonemia-ketogenesis and ketone body metabolism. J Dairy Sci. 1971 Jun;54(6):936–948. doi: 10.3168/jds.S0022-0302(71)85950-7. [DOI] [PubMed] [Google Scholar]
- Bergman E. N., Wolff J. E. Metabolism of volatile fatty acids by liver and portal-drained viscera in sheep. Am J Physiol. 1971 Aug;221(2):586–592. doi: 10.1152/ajplegacy.1971.221.2.586. [DOI] [PubMed] [Google Scholar]
- Bieberdorf F. A., Chernick S. S., Scow R. O. Effect of insulin and acute diabetes on plasma FFA and ketone bodies in the fasting rat. J Clin Invest. 1970 Sep;49(9):1685–1693. doi: 10.1172/JCI106386. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blom A. K., Hove K., Nedkvitne J. J. Plasma insulin and growth hormone concentrations in pregnant sheep II: post-absorptive levels in mid- and late pregnancy. Acta Endocrinol (Copenh) 1976 Jul;82(3):553–560. doi: 10.1530/acta.0.0820553. [DOI] [PubMed] [Google Scholar]
- Brockman R. P., Bergman E. N., Joo P. K., Manns J. G. Effects of glucagon and insulin on net hepatic metabolism of glucose precursors in sheep. Am J Physiol. 1975 Nov;229(5):1344–1349. doi: 10.1152/ajplegacy.1975.229.5.1344. [DOI] [PubMed] [Google Scholar]
- Brockman R. P. Effects of glucagon and insulin on lipolysis and ketogenesis in sheep. Can J Comp Med. 1976 Apr;40(2):166–170. [PMC free article] [PubMed] [Google Scholar]
- Brockman R. P. Roles of glucagon and insulin in the regulation of metabolism in ruminants. A review. Can Vet J. 1978 Mar;19(3):55–62. [PMC free article] [PubMed] [Google Scholar]
- Costa N. D., McIntosh G. H., Snoswell A. M. Production of endogenous acetate by the liver in lactating ewes. Aust J Biol Sci. 1976 Mar;29(1-2):33–42. [PubMed] [Google Scholar]
- Gerich J. E., Lorenzi M., Bier D. M., Schneider V., Tsalikian E., Karam J. H., Forsham P. H. Prevention of human diabetic ketoacidosis by somatostatin. Evidence for an essential role of glucagon. N Engl J Med. 1975 May 8;292(19):985–989. doi: 10.1056/NEJM197505082921901. [DOI] [PubMed] [Google Scholar]
- HIRD F. J., SYMONS R. H. The mode of formation of ketone bodies from butyrate by tissue from the rumen and omasum of the sheep. Biochim Biophys Acta. 1961 Jan 29;46:457–467. doi: 10.1016/0006-3002(61)90577-7. [DOI] [PubMed] [Google Scholar]
- Heitzman R. J., Hibbitt K. G., Mather I. The effects of thyroxine on hepatic gluconeogenesis and ketogenesis in dairy cows. Eur J Biochem. 1971 Aug 16;21(3):411–415. doi: 10.1111/j.1432-1033.1971.tb01485.x. [DOI] [PubMed] [Google Scholar]
- Hove K., Halse K. Absence of feeding-induced variations in plasma insulin in hypoglycaemic-ketonaemic cows. Acta Vet Scand. 1978;19(2):215–228. doi: 10.1186/BF03547627. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hove K. Maintenance of lactose secretion during acute insulin deficiency in lactating goats. Acta Physiol Scand. 1978 Jun;103(2):173–179. doi: 10.1111/j.1748-1716.1978.tb06205.x. [DOI] [PubMed] [Google Scholar]
- Hove K. Nocturnal plasma insulin levels in cows with varying levels of plasma ketone bodies; relations to plasma sugar and acetoacetate. Acta Endocrinol (Copenh) 1974 Jul;76(3):513–524. doi: 10.1530/acta.0.0760513. [DOI] [PubMed] [Google Scholar]
- Jarrett I. G., Filsell O. H., Ballard F. J. Metabolic and endocrine interrelationships in normal and diabetic sheep. Horm Metab Res. 1974;Suppl 4:111–116. [PubMed] [Google Scholar]
- Jarrett I. G., Filsell O. H., Ballard F. J. Utilization of oxidizable substrates by the sheep hind limb: effects of starvation and exercise. Metabolism. 1976 May;25(5):523–531. doi: 10.1016/0026-0495(76)90006-8. [DOI] [PubMed] [Google Scholar]
- KRONFELD D. S. GROWTH HORMONE-INDUCED KETOSIS IN THE COW. J Dairy Sci. 1965 Mar;48:342–346. doi: 10.3168/jds.s0022-0302(65)88225-x. [DOI] [PubMed] [Google Scholar]
- KRONFELD D. S., TOMBROPOULOS E. G., KLEIBER M. Glucose biokinetics in normal and ketitic cows. J Appl Physiol. 1959 Nov;14:1026–1028. doi: 10.1152/jappl.1959.14.6.1026. [DOI] [PubMed] [Google Scholar]
- Katz M. L., Bergman E. N. Hepatic and portal metabolism of glucose, free fatty acids, and ketone bodies in the sheep. Am J Physiol. 1969 Apr;216(4):953–960. doi: 10.1152/ajplegacy.1969.216.4.953. [DOI] [PubMed] [Google Scholar]
- Kaufman C. F., Bergman E. N. Renal glucose, free fatty acid, and ketone body metabolism in the unanesthetized sheep. Am J Physiol. 1971 Oct;221(4):967–972. doi: 10.1152/ajplegacy.1971.221.4.967. [DOI] [PubMed] [Google Scholar]
- Keller U., Chiasson J. L., Liljenquist J. E., Cherrington A. D., Jennings A. S., Crofford O. S. The roles of insulin, glucagon, and free fatty acids in the regulation of ketogenesis in dogs. Diabetes. 1977 Nov;26(11):1040–1051. doi: 10.2337/diab.26.11.1040. [DOI] [PubMed] [Google Scholar]
- Knowles S. E., Jarrett I. G., Filsell O. H., Ballard F. J. Production and utilization of acetate in mammals. Biochem J. 1974 Aug;142(2):401–411. doi: 10.1042/bj1420401. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kronfeld D. S. Hypoglycemia in ketotic cows. J Dairy Sci. 1971 Jun;54(6):949–961. doi: 10.3168/jds.S0022-0302(71)85951-9. [DOI] [PubMed] [Google Scholar]
- Kronfeld D. S., Raggi F., Ramberg C. F., Jr Mammary blood flow and ketone body metabolism in normal, fasted, and ketotic cows. Am J Physiol. 1968 Jul;215(1):218–227. doi: 10.1152/ajplegacy.1968.215.1.218. [DOI] [PubMed] [Google Scholar]
- Liljenquist J. E., Bomboy J. D., Lewis S. B., Sinclair-Smith B. C., Felts P. W., Lacy W. W., Crofford O. B., Liddle G. W. Effects of glucagon on lipolysis and ketogenesis in normal and diabetic men. J Clin Invest. 1974 Jan;53(1):190–197. doi: 10.1172/JCI107537. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindsay D. B., Setchell B. P. The oxidation of glucose, ketone bodies and acetate by the brain of normal and ketonaemic sheep. J Physiol. 1976 Aug;259(3):801–823. doi: 10.1113/jphysiol.1976.sp011496. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Manns J. G. Separation of pancreatic and gut glucagon-like immunoreactivity (G.L.I.) with observations on plasma concentrations of these hormones during lactation. Can J Physiol Pharmacol. 1972 Jun;50(6):554–560. doi: 10.1139/y72-083. [DOI] [PubMed] [Google Scholar]
- Mayes P. A., Felts J. M. Regulation of fat metabolism of the liver. Nature. 1967 Aug 12;215(5102):716–718. doi: 10.1038/215716a0. [DOI] [PubMed] [Google Scholar]
- McGarry J. D., Foster D. W. Hormonal control of ketogenesis. Biochemical considerations. Arch Intern Med. 1977 Apr;137(4):495–501. [PubMed] [Google Scholar]
- McGarry J. D., Foster D. W. The regulation of ketogenesis from oleic acid and the influence of antiketogenic agents. J Biol Chem. 1971 Oct 25;246(20):6247–6253. [PubMed] [Google Scholar]
- McGarry J. D., Robles-Valdes C., Foster D. W. Role of carnitine in hepatic ketogenesis. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4385–4388. doi: 10.1073/pnas.72.11.4385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- PENNINGTON R. J., SUTHERLAND T. M. Ketone-body production from various substrates by sheep-rumen epithelium. Biochem J. 1956 Jul;63(3):353–361. doi: 10.1042/bj0630353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patterson D. S. Depôt fat mobilization and liver lipogenesis and ketogenesis in ovine pregnancy toxaemia and the effects of corticotrophin administration. Res Vet Sci. 1966 Oct;7(4):484–492. [PubMed] [Google Scholar]
- Prior R. L., Christenson R. K. Insulin and glucose effects on glucose metabolism in pregnant and nonpregnant ewes. J Anim Sci. 1978 Jan;46(1):201–210. doi: 10.2527/jas1978.461201x. [DOI] [PubMed] [Google Scholar]
- Reid R. L. The physiopathology of undernourishment in pregnant sheep, with particular reference to pregnancy toxemia. Adv Vet Sci. 1968;12:163–238. [PubMed] [Google Scholar]
- Remesy C., Demigne C. Variations in some plasma metabolites from neoglucogenesis and ketogenesis in pregnant ewes in relation to diet. Ann Rech Vet. 1976;7(4):329–341. [PubMed] [Google Scholar]
- Roe W. E., Bergman E. N., Kon K. Absorption of ketone bodies and other metabolites via the portal blood of sheep. Am J Vet Res. 1966 May;27(118):729–736. [PubMed] [Google Scholar]
- Schade D. S., Eaton R. P. The contribution of endogenous insulin secretion to the ketogenic response to glucagon in man. Diabetologia. 1975 Dec;11(6):555–559. doi: 10.1007/BF01222106. [DOI] [PubMed] [Google Scholar]
- Schwalm J. W., Schultz L. H. Relationship of insulin concentration to blood metabolites in the dairy cow. J Dairy Sci. 1976 Feb;59(2):255–261. doi: 10.3168/jds.S0022-0302(76)84192-6. [DOI] [PubMed] [Google Scholar]
- Varnam G. C., Jeacock M. K., Shepherd D. A. Activities of ketone body utilising enzymes in tissues of fed and fasted sheep. Res Vet Sci. 1978 Jan;24(1):124–125. [PubMed] [Google Scholar]
- West C. E., Passey R. F. Effect of glucose load and of insulin on the metabolism of glucose and of palmitate in sheep. Biochem J. 1967 Jan;102(1):58–64. doi: 10.1042/bj1020058. [DOI] [PMC free article] [PubMed] [Google Scholar]