Studies of the Role of the Liver in Human Carbohydrate Metabolism by the Venous Catheter Technic. I. Normal Subjects Under Fasting Conditions and Following the Injection of Glucose1

Abstract

Previous observations on the role of the liver in carbohydrate metabolism have been made entirely in animals. Recently a method has been developed for obtaining specimens of hepatic venous blood and estimating the hepatic blood flow in human beings (1). This has supplied a tool which makes possible direct investigation of the activity of the liver during various phases of carbohydrate metabolism in man. The present paper deals with the application of this technic to the study of the response of the liver to the fasting state and to the intravenous injection of glucose solution. METHODSHepatic blood flow was estimated by the bromsulfalein method of Bradley (1) in some cases and in others by the urea method of Myers (2). In the few cases where blood flow determinations were not done, it was assumed that the hepatic blood flow was equal to the mean found in our other patients. The Glucose (0.5 gm./kg.) was administered intravenously in 250 ml. of distilled water over a period of 15 minutes.Blood samples were obtained simultaneously from the artery and hepatic vein before injection and 15, 45, and 60 minutes after the beginning of the infusion. The samples were taken into a sodium fluoride-oxalate mixture and were promptly treated to obtain the necessary filtrates. Glucose determinations were performed by the method of Nelson (3) using a 1:10 zinc hydroxide filtrate. In our laboratory this method has had a standard error of + 1.0 mg./100 ml. at a level of 100 mg./ 100 ml. Blood urea was determined on a 10% tungstic acid blood filtrate by the xanthydrol precipitation technic of Engel and Engel (5) and also on a 1: 200 dilution of urine. With this method, the standard error of the urea determination was 0.1 mg./100 ml. at a level of 20 mg./ 100 ml. All determinations were read on a Lumetron photoelectric calorimeter. CLINICAL MATERIALThe subjects of these experiments were 15 essentially normal volunteers who were convalescing from acute diseases. All were well nourished and had been on a diet supplying more than 200 gm. of carbohydrate for at least three days prior to the procedure. The subjects were fasted for 18 hours before the tests. In some cases 0.1 or 0.2 gm. of nembutal in 50 ml. of water was given orally about 30 minutes before the procedure. Every attempt was made to keep the subjects comfortable. Venipunctures and arterial punctures were done under procaine local anesthesia. The patients were usually at ease, and most of them dozed during the course of the experiment. As a result of the precautions taken, it seems unlikely that the normal physiological reactions to pain, fear, or anger significantly affected the observations. CALCULATIONSThe arterio-hepatic venous difference (A-HV) in mg./100 ml. is obtained by subtracting the hepatic venous from the arterial concentration. When the concentration is higher in the hepatic venous blood than in the arterial, the result is a negative quantity, indicating that the liver was losing the substance into the circulation. Where the A-HV value is positive, the liver ...

Amino acid balance across tissues of the forearm in postabsorptive man. Effects of insulin at two dose levels

“…For a man weighing 70 kg whose skeletal muscle comprises 40% of body weight, 0.43 moles/day would be released from this tissue. This estimate agrees well with the total quantity of amino acids consumed by the liver as calculated from direct measurements of both hepatic urea output (36) and amino acid uptake (37) in postabsorptive man. Moreover, agreement is good between the pattern of individual amino acids released by muscle and their pattern of uptake by the liver (37,38).…”

Splanchnic Uptake and Release of Energy Substrates in the Fasting Baboon Infant

“…Because hepatic vein catheterization has not proved technically feasible in this preparation, the following formula utilizing the Fick principle was employed to derive estimates of HV, based upon determinations of FLC, FSP, and substrate concentrations V2 and Vl. This formula cannot be validated in the neonatal baboon, but values for glucose production derived by this technique agree well with previous data for glucose turnover in the neonate and hepatic glucose production in adult humans (4,5,7,9,15). …”

Net Splanchnic Glucose Production in Normal Man and in Various Disease States 1

“…The only previous estimates in man of peripheral glucose utilization from measurement of the splanchnic glucose production are those of Bondy (5 If for purposes of calculation it is assumed that our control subjects remained fasting for 24 hours and maintained their net splanchnic glucose productions at the rate herein determined, then the mean glucose output of 65 mg. per minute per sq. M. amounts to a total production of 162 gms.…”

“…The recent introduction of the procedure of catheterization of the hepatic veins of man (2) has allowed estimation of the hepatic blood flow (3,4) and the collection of blood samples from those veins for the determination of the glucose difference between hepatic venous and arterial bloods. This technique has been used by Bondy (5,6) and ourselves (7) in the study of hepatic carbohydrate balance in normal and diabetic subjects.…”