ARS | Publication request: AMINO ACID, GLUCOSE, AND LIPID KINETICS AFTER PALLIATIVE RESECTION IN A PATIENT WITH GLUCAGONOMA SYNDROME

Submitted to: Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 20, 2001
Publication Date: June 20, 2001
Citation: BERNSTEIN, M., JAHOOR, F., TOWNSEND, C.M., KLEIN, S. AMINO ACID, GLUCOSE, AND LIPID KINETICS AFTER PALLIATIVE RESECTION IN A PATIENT WITH GLUCAGONOMA SYNDROME. METABOLISM. 2001. v. 50(6). p. 720-722.

Interpretive Summary: Glucagon is a hormone which causes the body to breakdown fat and protein at a fast rate and to convert some of the fat and protein to sugar. When people develop a condition called glucagonoma syndrome they have tumors in their livers that produce large amounts of this hormone. Over time the excessive glucagon causes them to lose a lot of body fat and muscle and become wasted. They also get high levels of blood sugar like patients with diabetes. To help these patients surgeons operate on them to remove as many of the tumors as possible. However, it is not known whether this surgery really brings their glucagon down and prevent them from breaking down body protein and fat and making excess sugar. In this study, we evaluated the effects of surgery on a patient with glucagon-producing tumor 25 days after surgery to see whether the patient was producing less glucagon and whether this lessened protein and fat breakdown rate and the rate at which sugar was made. We repeated the measurements when the patient was also getting a drug, somatostatin, which suppresses production of glucagon. We found that surgery alone did not lower glucagon or slow down the breakdown rate of fat and protein and their conversion to sugar. However, somatostatin decreased blood glucagon, reduced breakdown of body protein and fat and the rate at which sugar was made in the body. In these patients, somatostatin therapy can be an effective method to suppress secretion of glucagon and help alleviate the bad effects of the excess glucagon produced by these patients.

Technical Abstract: Glucagon excess causes catabolic changes, including enhanced glucose production, lipolysis, and amino acid oxidation. In this study, we evaluate the metabolic effects of debulking surgery on a patient with glucagon-producing tumor. Stable isotope tracer methods were used to measure glucose, glycerol, and alpha-ketoisocaproic acid (alpha KICA) rates of appearance (Ra) into plasma. Measurements were obtained 25 days after surgery in the basal state and during hormonal suppression of glucagon production by infusing somatostatin with insulin replacement. Basal plasma glucagon concentration (14,100 pg/mL) remained high after debulking surgery. Somatostatin infusion decreased plasma glucagon concentration to 6,735 pg/mL and basal substrate kinetics (alpha-KICA Ra from 1.97 to 1.48 micromol/kg/min; glucose Ra from 16.89 to 11.56 micromol/kg/min; and glycerol Ra from 3.33 to 2.74 micromol/kg/min). We conclude that debulking surgery fails to adequately suppress glucagon production and the alterations in substrate metabolism associated with excess glucagon. In these patients, somatostatin therapy can be an effective method to suppress secretion of glucagon and help attenuate its catabolic effects.