Inhibition of insulin secretion, but normal peripheral insulin sensitivity, in a patient with a malignant endocrine pancreatic tumour producing high amounts of an islet amyloid polypeptide-like molecule.
Islet amyloid polypeptide or amylin is a polypeptide secreted mainly from the pancreatic beta cells together with insulin upon stimulation. High levels of islet amyloid polypeptide have also been shown to increase the peripheral insulin resistance and consequently a role for islet amyloid polypeptide in the glucose homeostasis has been suggested. We have studied the glucose homeostasis in a patient with a malignant endocrine pancreatic tumour producing large amounts of an islet amyloid polypeptide-like molecule (about 400 times the upper reference level for islet amyloid polypeptide). This patient developed insulin-requiring diabetes mellitus shortly after the tumour diagnosis. Both intravenous and oral glucose tolerance tests revealed inhibited early responses in insulin and C-peptide release, but the insulin and C-peptide response to glucagon stimulation was less affected. Aneuglycaemic insulin clamp showed normal insulin-mediated glucose disposal. In vitro experiments, where isolated rat pancreatic islets were cultured with serum from the patient, showed a moderately decreased islet glucose oxidation rate and glucose-stimulated insulin release compared to islets cultured with serum from healthy subjects. However, culture of rat islets with normal human serum supplemented with synthetic rat islet amyloid polypeptide did not affect the glucose-stimulated insulin release. In conclusion, the observed effects show that the diabetic state in this patient was associated with an impaired glucose-stimulated insulin release but not with an increased peripheral insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Stridsberg
M
M
Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
Berne
C
C
Sandler
S
S
Wilander
E
E
Oberg
K
K
D000682:Amyloid / Q000096:biosynthesis* / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002478:Cells, Cultured; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood*; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000682:Amyloid; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D058228:Islet Amyloid Polypeptide