Pancreatectomised man: A model for diabetes without glucagon

Area of Science:

• Endocrinology
• Metabolic Disorders
• Diabetes Research

Background:

• The role of glucagon in maintaining hyperglycemia in diabetes mellitus is debated.
• Investigating extrapancreatic glucagon production is crucial for understanding diabetes pathophysiology.

Purpose of the Study:

• To investigate the role of glucagon in maintaining hyperglycemia in patients with and without a pancreas.
• To determine if extrapancreatic alpha cells contribute significantly to glucagon levels in humans.

Main Methods:

• Studied 5 totally pancreatectomized subjects and 5 insulin-dependent diabetic patients.
• Utilized a novel affinity chromatography technique to measure true basal glucagon levels.
• Administered arginine infusion to assess glucagon response.

Main Results:

• Pancreatectomized subjects had markedly elevated fasting plasma glucose (251 +/- 46 mg/dl) but near-zero basal glucagon (1.3 +/- 0.6 pmol/l).
• Arginine did not increase glucagon in pancreatectomized subjects.
• Insulin-dependent diabetics showed elevated basal glucagon (17.2 +/- 5.3 pmol/l) that significantly increased post-arginine infusion.

Conclusions:

• Pronounced hyperglycemia can occur independently of glucagon.
• Findings suggest a lack of significant functional extrapancreatic alpha cells in humans.
• Glucagon is likely not a primary driver of hyperglycemia in insulin-dependent diabetes.