The Significance of Ketosis

MacKay, Eaton M.

doi:10.1210/jcem-3-2-101

Cited by 27 publications

(3 citation statements)

References 55 publications

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“…In this manner the molar concentration of NEFA and ketones may rise and then be maintained within relatively narrow limits at a new elevated level without the danger of fatal ketosis. Such changes in the concentration of plasma ketones and NEFA have been described during starvation (4,5,27,29).…”

Section: Methodsmentioning

confidence: 76%

“…These changes occurred within 10 minutes before plasma ketone levels reached 3.5 mmoles per L and suggest that levels below this stimulate the secretion of endogenous insulin. Such stimulatory levels of plasma ketones occur during carbohydrate deprivation associated witlh either a high fat diet or complete starvation, where plasma ketone levels of 3.2 mmoles per L are not unusual and values as high as 6.5 mmoles per L may be found (2,4,(27)(28)(29)(30).…”

Section: Methodsmentioning

confidence: 99%

“…Although plasma ketones are known to rise to levels between 3.5 and 5.0 mmoles per L during starvation of similar duration (4,5,27,29), this relative and actual increase in plasma ketone concentration serves to increase the efficiency of ketones as a competitor of glucose for metabolism by the peripheral tissues and has been shown to inhibit peripheral glucose utilization. In previous, in vivo, studies from this laboratory (18,19), ketone infusions were noted to produce a 30%o reduction in the utilization of glucose by peripheral tissues.…”

Section: Methodsmentioning

confidence: 99%

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The Hypoglycemic Action of Ketones. II. Evidence for a Stimulatory Feedback of Ketones on the Pancreatic Beta Cells *

Madison¹,

Mebane²,

Unger³

et al. 1964

J. Clin. Invest.

223

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The effects of alterations in carbohydrate metabolism induced by starvation and insulin deprivation on hepatic ketone production and peripheral ketone utilization have been the subject of intensive investigation (1-12). Only scant attention, however, has been paid to the effects that hyperketonemia, in turn, might have on carbohydrate and fat metabolism. The conflicting results from such studies (13-17) have been reviewed recently (18). Studies in this laboratory, designed to define the effects of induced hyperketonemia on carbohydrate and fat metabolism (18,19), showed that iv infusions of ,8-hydroxybutyric acid, acetoacetic acid, or their sodium salts produced the following immediate changes in glucose and nonesterified fatty acid (NEFA) metabolism: 1) blood glucose concentration fell promptly, at times to distinctly hypoglycemic levels, 2) hepatic glucose output decreased sharply to less than 50% of control values, a reduction accounting entirely for the decrease in arterial glucose concentration, and 3) these changes in glucose metabolism were accompanied simultaneously by a greater than 50% fall in arterial plasma NEFA concentration. The qualitative similarity between ketone infusion and the slow iv administration of insulin (20) only on blood glucose concentration and hepatic glucose output but also on plasma NEFA concentration suggested the possibility that ketones produce these effects via stimulation of endogenous insulin secretion.The present studies were designed specifically to determine whether ketone bodies stimulate the pancreatic 8-cells, directly or indirectly, to secrete increased amounts of insulin. Two types of studies were performed: in the first group, the effects of hyperketonemia produced by infusions of 8-hydroxybutyrate and acetoacetate on blood glucose concentrations were compared in depancreatized dogs and in dogs with alloxan diabetes; in the second group of studies, the changes in pancreatic venous insulin concentrations were determined by immunoassay during infusions of ketones either into a femoral vein or into a branch of the pancreatic artery. MethodsIn the studies designed to compare the effects of ,3-hydroxybutyrate and acetoacetate on the arterial glucose concentration of totally diabetic depancreatized and partially diabetic alloxanized dogs, experiments were performed at least 2 weeks after alloxanization (21)

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Section: Methodsmentioning

confidence: 76%