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The Hepatic Extraction of Gastric Inhibitory Polypeptide and Insulin^*

JOHN B. HANKS, DANA K. ANDERSEN, JOYCE E. WISE, WILLIAM S. PUTNAM, WILLIAM C. MEYERS and R. SCOTT JONES

Departments of Surgery, Physiology, and Pediatrics, Duke University Medical Center and Veterans Administration Medical Center Durham, North Carolina 27710

Address all correspondence and requests for reprints to: John B. Hanks, M.D., Box 181, Department of Surgery, University of Virginia Medical Center, Charlottesville, Virginia 22908.

Abstract

The hepatic extractions of gastric inhibitory polypeptide (GIP) and insulin were determined using in vitro arid in vivo methods to assess the role of the liver in GIP metabolism and the possible effect of GIP on the hepatic extraction of insulin. During in vitro studies using the isolated perfused rat liver, infusion of GIP (2000 pg/ml) alone and in combination with porcine insulin (200 µU/ml) resulted in negligible hepatic extraction of immunoreactive GIP (IR-GIP) in both fed and fasted animals during either physiologically eugly-cemic or hyperglycemic perfusions. Hepatic extraction of insulin, however, ranged from 26–36% in fasted animals and from 7–25% in fed animals. Hepatic extraction of insulin and net hepatic glucose appearance were minimally affected by GIP. In vivo studies in awake dogs were then performed, in which simultaneous portal and peripheral venous levels of IR-GIP, immunoreactive insulin (IRI), and glucose were assessed after intraduodenal glucose administration. The portal to peripheral (PORT/PERI) venous ratio of endogenous IRI and IR-GIP reflected the findings of the in vitro studies; the PORT/PERI ratio of IRI levels rose from a basal value of 1.9 ± 0.3 to a peak of 3.7 ± 0.9, while the PORT/PERI ratio of IR-GIP levels rose from a basal value of 1.0 ± 0.1 to a peak of 1.4 ± 0.2, then rapidly returned to 1.0. The in vivo data are consistent with a continuous hepatic extraction of 40–50% of the insulin entering the liver and a negligible hepatic extraction of IR-GIP. We conclude that he-patic extraction of GIP in vitro or in vivo is minimal. In addition, while the fed state of the animal before infusion can result in changes in the in vitro hepatic extraction of insulin, GIP does not mediate these changes. (Endocrinology 115: 1011–1018, 1984)

Footnotes

^* Data were presented in part at the Third International Symposium on Gastrointestinal Hormones, Cambridge, England, September 1980, and at the American College of Surgeons Annual Clinical Congress, Atlanta, GA, October 1980. This work was supported by grants from the North Carolina United Way Fund, the NIH (AM-16421), and the V.A. (no. 4790).

Present address: Box 181, Department of Surgery, University of Virginia Medical Center, Charlottesville, Virginia 22908.

Present address: Departments of Medicine and Surgery, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203.

Present address: Department of Pediatrics, Peoria School of Medicine, University of Illinois College of Medicine, Peoria, Illinois 61656.

Received April 25, 1984.

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