This paper describes a new method for evaluating glucose metabolism in man using an oral glucose load. The procedure permits the calculation of a blood glucose disappearance rate constant (K) and thereby makes it possible to compare quantitatively the response to oral and intravenous glucose administration in a given individual. Ten metabolically normal adult humans were studied under carefully controlled conditions. Each received similar amounts (20 g) of glucose both orally and intravenously (2-7 days apart) by constant infusion for 1 hr. The effects on blood glucose disappearance rate constants (K) and plasma insulin concentrations (immunoassay) during and for 1 hr following the infusion were compared. Blood glucose concentrations and K values with the 2 routes of glucose administration were similar. In contrast, plasma insulin responses showed a significant difference: oral glucose resulted in a significant and sustained rise, whereas intravenous glucose was associated with a smaller and transient increase.The plasma insulin increase with intravenous glucose is considered to be due to the wellknown effect of hyperglycemia on insulin secretion. The greater and more sustained increase in plasma insulin with oral glucose is interpreted as evidence for an additional stimulus to insulin secretion, possibly a gastrointestinal or liver factor triggered by alimentary glucose. (J Clin Endocr 24: 1076, 1964 B OTH ORAL and intravenous glucose tolerance tests are widely used to evaluate glucose metabolism in man. Intravenous methods permit the calculation of a specific rate constant for glucose utilization (K) from a relationship of blood glucose and time, whereas present oral methods do not allow for such a quantitative expression of data and are handicapped by the variable of intestinal absorption. Thus, there are no published reports on a quantitative comparison of oral and intravenous glucose utilization in man.This paper describes a new method for

In an effort to answer many unresolved questions concerning orthotopic homotransplantation of the canine liver, a complete reappraisal of this preparation was under-taken in early 1964 in both the untreated and modified host. A particular effort was made to (A) reduce the operative mortality; (B) interpret the significance of pathologic changes in the homograft and in the recipient tissues; (C) define the presence or absence of a graft-host reaction; (D) study the effect of variations in therapy upon results; (E) assess the hepatotoxic properties of azathioprine; (F) determine if and with what regularity hepatic rejection could be reversed and chronic survival attained; and (G) find if and when a state of relative host-graft non-reactivity developed some time after homotransplantation. METHODS Mongrel dogs weighing 8.3 to 27.3 kilograms were used. All animals had hematologic and liver function determinations before and at regular intervals after the experiments were begun. Red cell survival studies were performed with a Cr 51 technique. 6 Tetracycline and chloramphenicol were routinely administered. Azathioprine * was employed in most experiments with a dose of 2 to 8 mg. per kilogram per day. Insofar as possible, the induction of leukopenia was avoided. Azathioprine and antibiotic therapy was discontinued at 120 days in all surviving animals. Other variations in therapy are described below. Tissues were examined with light and electron microscopy. For homotransplantation, livers were obtained from donors of dissimilar appearance, but of approximately the same weight as the recipients. Prior to removal, the donor liver was cooled by perfusion of chilled Ringer's lactate solution through the portal vein. The technique of transplantation 24 resulted in an essentially normal blood supply (Fig. 1). The intervals of ischemia were almost all less than one hour. Cholecystoduodenostomy was established for internal biliary drainage. Azathioprine toxicity study In 18 non-transplanted dogs the effects of 40 days of azathioprine were studied. The animals were divided into 3 groups of 6 each which received: Group I. Daily azathioprine (2 to 4 mg. per kilogram).

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Evidence is presented to show that the extreme variation in rate constants for blood glucose disappearance reported by different laboratories is due to the use of an incorrect equation and/or an incorrect method of data analysis. It is demonstrated that graphic (semi-log) methods are too insensitive to be used to justify equations describing blood glucose disappearance. The correct equation is shown to be one of exponential form containing an added constant term which in the normal subject is significantly less than the fasting level of blood glucose. A new method of data analysis (slope analysis) is described which results in the same specific rate constant, K, regardless of the equation employed. This method is made practical by the introduction of a mechanical slope reader which eliminates excessive calculations.

The transfer of certain electrolytes (Na22, Cl36, K42 and P32O4) from the isolated urinary bladder to the plasma compartment was studied in the dog. The rate of transfer was shown to be a function of the ph of the bladder contents over a range of 5 through 8. It was also shown that the rate of transfer was decreased by addition of common ion. Na22 and Cl36 showed greater rates of transfer than did P32O4 and K42. However, ph influences held true for all isotopes. No active mechanism of transfer could be demonstrated and it was concluded that ion exchange was the probable explanation for the transfer process.