Altered glucose dependence of glucagon-like peptide I(7-36)-induced insulin secretion from the Zucker (fa/fa) rat pancreas.
In previous studies on the enteroinsular axis in Zucker rats, it was found that glucose-dependent insulinotropic polypeptide (GIP) levels were normal in obese animals, but the glucose threshold for the insulinotropic action of GIP in the perfused rat pancreas was reduced. Glucagon-like peptide I (GLP-I)(7-36) is also an important incretin, and in the current study, glucose, insulin, and immunoreactive (IR)-COOH-terminal GLP-I responses to oral glucose were compared in lean (Fa/?) and obese (fa/fa) rats. In addition, the concentration thresholds for stimulation and glucose dependence of perfused pancreases to GLP-I(7-36) were examined. Glucose responses to oral glucose were similar in fa/fa and Fa/? rats. Obese animals were hyperinsulinemic when fasting and after oral glucose. Significant increases in IR-GLP-I levels in response to glucose were only observed in fa/fa rats. Perfused pancreases from fa/fa rats hypersecreted insulin at all glucose concentrations. In the presence of 4.4 mmol/l glucose, GLP-I(7-36) increased insulin secretion in fa/fa pancreases approximately 25-fold, whereas there was only a 5-fold increase in Fa/? pancreases. Pancreases from fa/fa rats, perfused with a glucose gradient (2.8-11 mmol/l) in the presence of GLP-I(7-36), responded with an immediate increase in insulin secretion, i.e., at a glucose concentration of 2.8 mmol/l, whereas Fa/? pancreases required a minimum of 4.22 mmol/l glucose for stimulation. With high glucose (16.7 mmol/l), both fa/fa and Fa/? rat pancreases exhibited similar responsiveness to GLP-I(7-36), having thresholds of < 50 pmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
Jia
X
X
Department of Physiology, University of British Columbia, Vancouver, Canada.
Elliott
R
R
Kwok
Y N
YN
Pederson
R A
RA
McIntosh
C H
CH
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D011924:Rats, Zucker
D007328:Insulin; D010446:Peptide Fragments; C061970:glucagon-like peptide 1 (7-36); D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose