Reduced GLP-1 and insulin responses and glucose intolerance after gastric glucose in GRP receptor-deleted mice.
By applying a newly developed ELISA technique for determining biologically active intact glucagon-like peptide [GLP-1, GLP-1-(7-36)amide] in mouse, plasma baseline GLP-1 in normal NMRI mice was found to be normally distributed (4.5 +/- 0.3 pmol/l; n = 72). In anesthetized mice, gastric glucose (50 or 150 mg) increased plasma GLP-1 levels two- to threefold (P < 0.01). The simultaneous increase in plasma insulin correlated to the 10-min GLP-1 levels (r = 0.36, P < 0.001; n = 12). C57BL/6J mice deleted of the gastrin-releasing peptide (GRP) receptor by genetic targeting had impaired glucose tolerance (P = 0.030) and reduced early (10 min) insulin response (P = 0.044) to gastric glucose compared with wild-type controls. Also, the GLP-1 response to gastric glucose was significantly lower in the GRP receptor-deleted mice than in the controls (P = 0.045). In conclusion, this study has shown that 1) plasma levels of intact GLP-1 increase dose dependently on gastric glucose challenge in correlation with increased insulin levels in mice, and 2) intact GRP receptors are required for normal GLP-1 and insulin responses and glucose tolerance after gastric glucose in mice.
Persson
K
K
Department of Medicine, Lund University, Malmö, SE-205 02 Sweden.
Gingerich
R L
RL
Nayak
S
S
Wada
K
K
Wada
E
E
Ahrén
B
B
D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005751:Gastric Lavage; D005934:Glucagon / Q000097:blood*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000008:administration & dosage*; D018149:Glucose Intolerance; D007328:Insulin / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000097:blood*; D011498:Protein Precursors / Q000097:blood*; D018004:Receptors, Bombesin / Q000235:genetics / Q000502:physiology*
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D018004:Receptors, Bombesin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose