Impaired Glucose-Induced Glucagon Suppression after Partial Pancreatectomy

• Published in: The journal of clinical endocrinology and metabolism 2009-08, Vol.94 (8), p.2857-2863
• Main Authors: Schrader, Henning, Menge, Bjoern A., Breuer, Thomas G. K., Ritter, Peter R., Uhl, Waldemar, Schmidt, Wolfgang E., Holst, Jens J., Meier, Juris J.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Blood Glucose - analysis; C-Peptide - analysis; Endocrinopathies; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glucagon - blood; Glucagon-Secreting Cells - physiology; Glucose - pharmacology; Humans; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - pathology; Male; Medical sciences; Middle Aged; Pancreatectomy; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2009-0826

Introduction: The glucose-induced decline in glucagon levels is often lost in patients with type 2 diabetes. It is unclear whether this is due to an independent defect in α-cell function or secondary to the impairment in insulin secretion. We examined whether a partial pancreatectomy in humans would also impair postchallenge glucagon concentrations and, if so, whether this could be attributed to the reduction in insulin levels. Patients and Methods: Thirty-six patients with pancreatic tumours or chronic pancreatitis were studied before and after approximately 50% pancreatectomy with a 240-min oral glucose challenge, and the plasma concentrations of glucose, insulin, C-peptide, and glucagon were determined. Results: Fasting and postchallenge insulin and C-peptide levels were significantly lower after partial pancreatectomy (P < 0.0001). Likewise, fasting glucagon concentrations tended to be lower after the intervention (P = 0.11). Oral glucose ingestion elicited a decline in glucagon concentrations before surgery (P < 0.0001), but this was lost after partial pancreatectomy (P < 0.01 vs. preoperative values). The loss of glucose-induced glucagon suppression was found after both pancreatic head (P < 0.001) and tail (P < 0.05) resection. The glucose-induced changes in glucagon levels were closely correlated to the respective increments in insulin and C-peptide concentrations (P < 0.01). Conclusions: The glucose-induced suppression in glucagon levels is lost after a 50% partial pancreatectomy in humans. This suggests that impaired α-cell function in patients with type 2 diabetes may also be secondary to reduced β-cell mass. Alterations in glucagon regulation should be considered as a potential side effect of partial pancreatectomies. The glucose-induced suppression of glucagon secretion appears to be lost after hemipancreatectomy in humans.