Evidence of cosecretion of islet amyloid polypeptide and insulin by beta-cells.
Islet amyloid polypeptide (IAPP) has been identified as the major constituent of the pancreatic amyloid of non-insulin-dependent diabetes mellitus (NIDDM) and is also present in normal beta-cell secretory granules. To determine whether IAPP is a pancreatic secretory product, we measured the quantity of IAPP-like immunoreactivity (IAPP-LI), insulin, and glucagon released into 5 ml of incubation medium during a 2-h incubation of monolayer cultures (n = 5) of neonatal (3- to 5-day-old) Sprague-Dawley rat pancreases under three conditions: 1.67 mM glucose, 16.7 mM glucose, and 16.7 mM glucose plus 10 mM arginine and 0.1 mM isobutylmethylxanthine (IBMX). The quantity of IAPP-LI, insulin, and glucagon in the cell extract was also determined. Mean +/- SE IAPP-LI in the incubation medium increased from 0.041 +/- 0.003 pmol in 1.67 mM glucose to 0.168 +/- 0.029 pmol in 16.7 mM glucose (P less than 0.05) and 1.02 +/- 0.06 pmol in 16.7 mM glucose plus arginine and IBMX (P less than 0.05 vs. 1.67 or 16.7 mM glucose). Insulin secretion increased similarly from 4.34 +/- 0.27 to 20.2 +/- 0.6 pmol (P less than 0.05) and then to 135 +/- 5 pmol (P less than 0.05 vs. 1.67 or 16.7 mM glucose). Glucagon release tended to decrease with the increase in glucose concentration (0.39 +/- 0.01 vs. 0.33 +/- 0.02 pmol, P less than 0.1), whereas with the addition of arginine and IBMX to high glucose, glucagon release increased to 1.32 +/- 0.03 pmol (P less than 0.05 vs. 1.67 or 16.7 mM glucose).(ABSTRACT TRUNCATED AT 250 WORDS)
Kahn
S E
SE
Department of Medicine, University of Washington, Seattle.
D'Alessio
D A
DA
Schwartz
M W
MW
Fujimoto
W Y
WY
Ensinck
J W
JW
Taborsky
G J
GJ
Porte
D
D
D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D005947:Glucose