Elevated glucagon-like peptide-1 plasma levels, as a possible adaptive response, in diabetic NOD mice.
The incretin glucagon-like peptide-1 (GLP-1) and other GLP-1 receptor agonists have been shown to cause both antiapoptotic as well as regenerative effects on beta-cells in different animal models for diabetes. Our aim of this study was to test the hypothesis that spontaneously diabetic non obese diabetic (NOD) mice show an altered expression of GLP-1 compared to normoglycemic age-matched controls as a consequence of a diabetic state. To do this we used an ELISA prototype for mouse GLP-1 to measure plasma total GLP-1 from recently diabetic NOD mice as well as from age-matched normoglycemic NOD mice (controls). We also stained sections of pancreatic glands for GLP-1 from diabetic NOD mice and controls. We found increased levels of plasma total GLP-1 in diabetic NOD mice, when compared to control mice, both from non-fasted mice and from mice fasted for 2h. Furthermore, diabetic NOD mice displayed a higher GLP-1 response to an oral glucose tolerance test, compared to control mice. We also found that sections of pancreatic glands from diabetic NOD mice had an increased GLP-1 positive islet area in regard to relative islet area (i.e. total islet area / total pancreas area of the sections) compared to control mice. To our knowledge, this study is the first to show increased levels of GLP-1 in plasma in spontaneously diabetic NOD mice. We suggest that these results might represent a compensatory mechanism of the diabetic NOD mice to counteract beta-cell loss and hyperglycemia.
Department of Medical Cell Biology, Uppsala University, Biomedicum, P.O. Box 571, SE-75123 Uppsala, Sweden. Tobias.Rydgren@mcb.uu.se
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Rydgren
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Börjesson
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Carlsson
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Sandler
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood* / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D052216:Glucagon-Like Peptide 1