Pancreatic alpha-cell function in diabetic hemochromatotic subjects

Area of Science:

• Endocrinology
• Metabolic Disorders
• Gastroenterology

Background:

• Idiopathic hemochromatosis is associated with carbohydrate intolerance.
• The exact cause of this intolerance, particularly concerning pancreatic islet function, requires further investigation.

Purpose of the Study:

• To investigate the glucose, insulin, C-peptide, and glucagon responses to arginine stimulation in patients with hemochromatosis and other conditions causing carbohydrate intolerance.
• To differentiate the etiology of carbohydrate intolerance in hemochromatosis from other diabetic states.

Main Methods:

• Arginine (0.5 g/kg) was infused over 30 minutes in lean normal subjects, insulin-requiring subjects with hemochromatosis, genetic diabetes, total pancreatectomy, and non-diabetic cirrhotic subjects.
• Serum glucose, insulin, C-peptide, and glucagon levels were measured using RIA and glucose oxidase techniques.

Main Results:

• Hemochromatotic and genetic diabetic subjects exhibited subnormal C-peptide peak responses to arginine stimulation compared to normal subjects.
• Subjects with hemochromatosis, diabetes, and cirrhosis showed significantly higher basal and stimulated glucagon levels than normal subjects.
• Pancreatectomized subjects demonstrated no glucagon or C-peptide response to arginine, confirming the assay's sensitivity.

Conclusions:

• The impaired C-peptide response in hemochromatosis suggests islet cell dysfunction.
• Elevated glucagon levels in hemochromatosis, diabetes, and cirrhosis indicate a generalized dysregulation of glucagon secretion.
• Generalized islet cell destruction is unlikely to be the primary cause of diabetes in hemochromatosis.