Clinical Science and Molecular Medicine (19 78) 54,107-109
SHORT
COMMUNICATION
The metabolic response to galactose as a measure of hepatic glucose release in man G. R O Y L E , M. G. W. K E T T L E W E L L , V E R A I L I C 1 " A N D D . H. W I L L I A M S O N * " Nujfield Department of Surgery, and ^Metabolic Research Laboratory, Nujfield Department of Clinical Medicine, Radclijfe Infirmary, Oxford, U.K.
{Received20 June 1977; accepted!! September 1977)
function, and also as an aid to the diagnosis of disorders of glycogen metabolism, along with measurements of blood glucose and lactate. In glycogen storage disease type I (absence of glucose 6-phosphatase, EC 3.1.3.9) injection of galactose results in no rise in blood glucose but a marked increase in blood lactate, presumably due to increased hepatic glycolysis (Schwartz, Ashmore & Renold, 1957). In contrast, in glycogen synthase (EC 2.4.1.11) deficiency galactose administration results in both hyperglycaemia and hyperlactataemia (Dykes & Spencer-Peet, 1972; Aynsley-Green, Williamson & Gitzelmann, 1977). We have investigated the metabolic response to galactose under different physiological conditions in normal adult man as a possible indicator of hepatic carbohydrate metabolism. We have measured the rate of disappearance of galactose together with changes in blood glucose and lactate in the same patients, both 90 min after a meal and also after an overnight fast.
Summary 1. Galactose utilization after intravenous injec tion was measured in fed and fasted man together with changes in blood glucose, lactate and insulin. 2. Feeding did not alter blood galactose half-life. 3. The mean increases in blood glucose and lac tate were greater in the fasted subjects but their concentrations reached similar values in both fed and fasted states. 4. Plasma insulin increased after galactose in the fasted state, but there was no change in the fed state, indicating that galactose is not insulinogenic. 5. After an intravenous galactose load in the fed state insulin appears to inhibit hepatic glucose release. 6. An intravenous galactose test might be a useful measure of hepatic glucose release under different physiological and pathological conditions. Key words: galactose, glucose, insulin, lactate, liver.
Methods Introduction Subjects Galactose is predominantly metabolized in the liver, where it can be converted into glycogen or released as glucose, pyruvate and lactate (Fischer & Weinland, 1965; Cohn & Segal, 1973). The rate of galactose removal has been used as a test of liver Correspondence: Mr G. Royle. Nuffield Department of Surgery. Radcliffe Infirmary. Oxford OX2 6HE, U.K.
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Nine patients (six males, three females) admitted for elective surgery (three cholecystectomy, two femoro-popliteal bypass grafts, two haemorrhoidectomy, one rectal prolapse, one mastectomy; age range 19—68 years; mean 50 years) were studied both 90 min after a standard meal and again after a 12 h overnight fast. None of the patients had
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malignant disease or diabetes mellitus, and none was receiving drugs known to alter carbohydrate metabolism. They were studied before surgery and on the day of discharge from hospital (8-10 days after surgery). Five patients were studied in the fed state and four in the fasted state before surgery. The project was approved by the Ethics Committee of the Radcliffe Infirmary and the procedure fully explained to the patients before their permission was sought.
Procedure D-Galactose (100 ml of 20%, w/v, solution) was injected at time 0 into an antecubital vein, over 4-6 min via an indwelling cannula. Venous samples (2 ml) were withdrawn without stasis via a threeway tap at - 1 0 , - 5 , +10, +15, +20, +25 and + 30 min. The samples were immediately deproteinized with 5 ml of cold 10% (w/v) per chloric acid. Heparinized blood (5 ml) for separation of plasma was also taken at - 5 and +30 min. The neutralized supernatant from the deproteinized blood was analysed enzymically for whole blood glucose (Slein, 1963), galactose (Kurz & Wallenfels, 1974) and lactate (Hohorst, Kreutz & Bücher, 1959). Immunoreactive insulin was estimated by a double-antibody technique (Albano, Ekins, Maritz & Turner, 1972). Blood galactose half-life was calculated from the iemi-logarithmic plot of its disappearance curve. Galactose con centrations ranged between 8 and 1 mmol/1 during the period +10 to +30 min. The decay curve was exponential. The mean glucose and lactate changes over 30 min in the fed and fasted states were calculated from the individual incremental areas of glucose and lactate change against time. The baseline values were obtained by averaging the values of the — 10 to —5 min samples. Values are expressed as mean ± SEM (« = 9). Comparisons were made by paired i-tests.
(0-62 ± 0 0 8 mmol/1; / > < 0 0 2 ) in the fasted state. Basal lactate was lower after the fast (0-59 + 0-05 vs 1-0 ±0-10 mmol/1; P
SHORT
COMMUNICATION
The metabolic response to galactose as a measure of hepatic glucose release in man G. R O Y L E , M. G. W. K E T T L E W E L L , V E R A I L I C 1 " A N D D . H. W I L L I A M S O N * " Nujfield Department of Surgery, and ^Metabolic Research Laboratory, Nujfield Department of Clinical Medicine, Radclijfe Infirmary, Oxford, U.K.
{Received20 June 1977; accepted!! September 1977)
function, and also as an aid to the diagnosis of disorders of glycogen metabolism, along with measurements of blood glucose and lactate. In glycogen storage disease type I (absence of glucose 6-phosphatase, EC 3.1.3.9) injection of galactose results in no rise in blood glucose but a marked increase in blood lactate, presumably due to increased hepatic glycolysis (Schwartz, Ashmore & Renold, 1957). In contrast, in glycogen synthase (EC 2.4.1.11) deficiency galactose administration results in both hyperglycaemia and hyperlactataemia (Dykes & Spencer-Peet, 1972; Aynsley-Green, Williamson & Gitzelmann, 1977). We have investigated the metabolic response to galactose under different physiological conditions in normal adult man as a possible indicator of hepatic carbohydrate metabolism. We have measured the rate of disappearance of galactose together with changes in blood glucose and lactate in the same patients, both 90 min after a meal and also after an overnight fast.
Summary 1. Galactose utilization after intravenous injec tion was measured in fed and fasted man together with changes in blood glucose, lactate and insulin. 2. Feeding did not alter blood galactose half-life. 3. The mean increases in blood glucose and lac tate were greater in the fasted subjects but their concentrations reached similar values in both fed and fasted states. 4. Plasma insulin increased after galactose in the fasted state, but there was no change in the fed state, indicating that galactose is not insulinogenic. 5. After an intravenous galactose load in the fed state insulin appears to inhibit hepatic glucose release. 6. An intravenous galactose test might be a useful measure of hepatic glucose release under different physiological and pathological conditions. Key words: galactose, glucose, insulin, lactate, liver.
Methods Introduction Subjects Galactose is predominantly metabolized in the liver, where it can be converted into glycogen or released as glucose, pyruvate and lactate (Fischer & Weinland, 1965; Cohn & Segal, 1973). The rate of galactose removal has been used as a test of liver Correspondence: Mr G. Royle. Nuffield Department of Surgery. Radcliffe Infirmary. Oxford OX2 6HE, U.K.
107
Nine patients (six males, three females) admitted for elective surgery (three cholecystectomy, two femoro-popliteal bypass grafts, two haemorrhoidectomy, one rectal prolapse, one mastectomy; age range 19—68 years; mean 50 years) were studied both 90 min after a standard meal and again after a 12 h overnight fast. None of the patients had
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G. Royle et al.
malignant disease or diabetes mellitus, and none was receiving drugs known to alter carbohydrate metabolism. They were studied before surgery and on the day of discharge from hospital (8-10 days after surgery). Five patients were studied in the fed state and four in the fasted state before surgery. The project was approved by the Ethics Committee of the Radcliffe Infirmary and the procedure fully explained to the patients before their permission was sought.
Procedure D-Galactose (100 ml of 20%, w/v, solution) was injected at time 0 into an antecubital vein, over 4-6 min via an indwelling cannula. Venous samples (2 ml) were withdrawn without stasis via a threeway tap at - 1 0 , - 5 , +10, +15, +20, +25 and + 30 min. The samples were immediately deproteinized with 5 ml of cold 10% (w/v) per chloric acid. Heparinized blood (5 ml) for separation of plasma was also taken at - 5 and +30 min. The neutralized supernatant from the deproteinized blood was analysed enzymically for whole blood glucose (Slein, 1963), galactose (Kurz & Wallenfels, 1974) and lactate (Hohorst, Kreutz & Bücher, 1959). Immunoreactive insulin was estimated by a double-antibody technique (Albano, Ekins, Maritz & Turner, 1972). Blood galactose half-life was calculated from the iemi-logarithmic plot of its disappearance curve. Galactose con centrations ranged between 8 and 1 mmol/1 during the period +10 to +30 min. The decay curve was exponential. The mean glucose and lactate changes over 30 min in the fed and fasted states were calculated from the individual incremental areas of glucose and lactate change against time. The baseline values were obtained by averaging the values of the — 10 to —5 min samples. Values are expressed as mean ± SEM (« = 9). Comparisons were made by paired i-tests.
(0-62 ± 0 0 8 mmol/1; / > < 0 0 2 ) in the fasted state. Basal lactate was lower after the fast (0-59 + 0-05 vs 1-0 ±0-10 mmol/1; P
