This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stingl, H. Articles by Roden, M. Search for Related Content PubMed PubMed Citation Articles by Stingl, H. Articles by Roden, M.

Reduction of Hepatic Glycogen Synthesis and Breakdown in Patients with Agenesis of the Dorsal Pancreas

Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna (H.S., M.K., E.B., M.G.B., M.R.), A-1090 Vienna, Austria; Department of Internal Medicine, University of Graz (W.J.S., T.L.), A-8036 Graz, Austria; and Institute of Systems Science and Biomedical Engineering, University of Padova (G.P.), I-35127 Padova, Italy

Address all correspondence and requests for reprints to: Michael Roden, M.D., Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna Medical School, General Hospital of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. E-mail: michael.roden{at}akh-wien.ac.at.

Abstract

In a family with agenesis of the dorsal pancreas only the mother presents with insulin-dependent diabetes mellitus, whereas her sons are glucose tolerant. We examined whether metabolic defects can be detected early in this disease. Plasma glucose profiles were obtained from patients with dorsal pancreas agenesis and from matched healthy subjects. Hepatic glycogen synthesis and breakdown were determined from the time course of glycogen concentrations using noninvasive ¹³C nuclear magnetic resonance spectroscopy. Gluconeogenesis was calculated from the difference between glucose production (measured with D-[6,6-²H₂]glucose) and glycogen breakdown. Frequently sampled iv glucose tolerance tests were performed to assess insulin secretion and sensitivity. The mean plasma glucose level was higher (12.9 ± 0.4 vs. 5.9 ± 0.1 mmol/liter), whereas the peak plasma insulin level was lower (236 vs. 397 ± 23 pmol/liter) in the diabetic mother than in her nondiabetic sons and healthy subjects. In all patients, however, glycogen synthesis and breakdown were reduced by approximately 55% (P < 0.05) and 40% (P < 0.02), respectively. Gluconeogenesis (6.8 ± 0.8 vs. 4.2 ± 0.3 µmol/kg·min; P < 0.05) and hepatic insulin clearance (6.8 ± 1.3 vs. 2.8 ± 1.0 ml/kg·min) were increased in all patients.

In conclusion, patients with complete agenesis of the dorsal pancreas exhibit marked defects in hepatic glycogen metabolism, which are present even in the nondiabetic offspring.

This article has been cited by other articles:

				O. Kunert, H. Stingl, E. Rosian, M. Krssak, E. Bernroider, W. Seebacher, K. Zangger, P. Staehr, V. Chandramouli, B.R. Landau, et al. Measurement of Fractional Whole-Body Gluconeogenesis in Humans From Blood Samples Using 2H Nuclear Magnetic Resonance Spectroscopy Diabetes, October 1, 2003; 52(10): 2475 - 2482. [Abstract] [Full Text] [PDF]