Lack of effect of parathyroid hormone on hepatic glucose metabolism in the dog

It has been suggested that raised levels of parathyroid hormone (PTH) may induce glucose intolerance and impair insulin action in primary as well as secondary hyperparathyroidism. Furthermore, PTH is known to stimulate glycogenolysis in isolated hepatocytes and renal cortical cells. We administered a bolus of bovine 1:84 PTH to 8 awake dogs, and measured hepatic glucose production by the primed-constant 3H-3-Glucose infusion technique for 2 hr. PTH injection had no effect on fasting plasma glucose concentration or hepatic glucose production. Plasma insulin and glucagon, serum ionized and total calcium, and serum phosphate did not show any significant change following PTH administration. Synthetic bovine 1:34 PTH, administered to another 3 dogs using the same experimental protocol, also failed to affect any of the measured parameters. To investigate the possible synergism between PTH and other glycoactive hormones, we infused glucagon (3 ng/min · kg, 5 dogs) or epinephrine (0.1 ng/min · kg, 6 dogs) with or without 1:84 PTH in matched experiments. Glucagon alone caused a 22% rise (p < 0.01) in plasma glucose concentration and a 27% rise (p < 0.05) in hepatic glucose production; epinephrine alone induced a 54% rise (p < 0.01) in plasma glucose and a 39% increase (p < 0.01) in glucose production. When PTH injection was combined with glucagon or epinephrine infusion, no further stimulation of hepatic glucose production was observed. In another 6 awake dogs with portal and hepatic venous and arterial catheters, the hepatic response to PTH was determined both by measuring net hepatic glucose balance (hepatic plasma flow times transhepatic glucose concentration difference) and by tracer methodology. While the two techniques showed excellent agreement, both failed to show any effect of PTH. Four dogs in this group received 1:84 PTH obtained from commercial source. In all the other studies here reported, 1:84 PTH prepared in our laboratory was used. Both preparations caused a marked rise in phosphate excretion in dogs, and had the same potency as standard synthetic bovine 1:34 PTH in stimulating c-AMP generation by isolated renal tubular membranes. We conclude that the acute administration of PTH does not stimulate hepatic glucose production in the dog.