Effect of Intact Parathyroid Hormone on Hepatic Glucose Release in the Dog

Keith A. Hruska; Joan Blondin; Raymond Bass; Julio Santiago; Lorraine Thomas; Paul Altsheler; Kevin Martin; Saulo Klahr

doi:10.1172/JCI109538

Effect of Intact Parathyroid Hormone on Hepatic Glucose Release in the Dog

Keith A. Hruska, Joan Blondin, Raymond Bass, Julio Santiago, Lorraine Thomas, Paul Altsheler, Kevin Martin, and Saulo Klahr

Published October 1, 1979 - More info

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Abstract

The liver has been shown to remove parathyroid hormone (PTH) from its arterial circulation by a mechanism that is selective for the intact form of the peptide (PTH 1-84). The present studies demonstrate that PTH has biologic effects on the liver in vivo. Bovine PTH 1-84 stimulated hepatic glucose release in dogs with indwelling hepatic vein catheters from basal values of 31±8 to 68±9 mg/min per kg after bolus injections of PTH. The effect on hepatic glucose release was apparent by 5 min and persisted for the 80 min of observation. The NH₂-terminal PTH fragment (syn b-PTH 1-34) had no effect. Bovine PTH 1-84 administered in doses designed to produce circulating levels of immunoreactive PTH similar to the endogenous levels observed in uremic dogs also increased the incorporation of ¹⁴C from infused [¹⁴C]alanine into glucose, and increased estimated hepatic uptake of both chemical and [¹⁴C]alanine, while increasing hepatic glucose release. Thus, administration of “physiologic levels” of b-PTH 1-84 stimulated hepatic glucose release in part through increased gluconeogenesis in vivo, whereas syn b-PTH 1-34 had no demonstrable effect. Circulating levels of insulin rose after PTH administration, an increase which presumably represents a secondary response to the rise in glucose release.

These results suggest that the liver is a target organ of PTH, and that PTH might potentially alter carbohydrate metabolism during hypersecretion. They also suggest that hepatic uptake of PTH may be related in part to production of a specific biologic effect rather than just simple peptide degradation.