Effects of prolonged exendin-4 administration on entero-insular axis of normal and streptozotocin-induced diabetic rats.
The effects of the glucagon-like peptide 1 (GLP-1) receptor agonist exendin-4 (EX4) and antagonist EX4(9-39) EX4-A on entero-insular axis have been investigated in normoglycemic and streptozotocin (STZ)-induced diabetic rats. Rats were administered daily subcutaneous injections of 1 nmol/kg EX4 and/or EX4-A for 7 days, and were decapitated 3 h after the last injection. In STZ-untreated rats, EX4 reduced body-weight (BW) gain and raised glycemia, and the effects were prevented by EX4-A; conversely, EX4 did not alter plasma concentrations of insulin, glucagon and leptin. STZ-treated rats displayed body and hematochemical alterations typical of experimental diabetes: decrease in BW and insulin blood level, coupled with normal glucagon plasma concentration and marked hyperglycemia. In diabetic rats, both EX4 and EX4-A decreased BW gain, thereby suggesting a mechanism at least in part independent of GLP-1 receptors. EX4 did not alter glucagon blood level, but decreased glycemia and raised insulin and leptin plasma levels. These effects were annulled by EX4-A, which indicates that they occur through the activation of GLP-1 receptors. Collectively, our findings add support to the view that EX4 can be considered an important therapeutical tool to improve glucose metabolism in diabetes.
Malendowicz
Ludwik K
LK
Department of Histology and Embryology, Karol Marcinkowski University of Medical Sciences, PL-60781 Poznan, Poland.
Macchi
Carlo
C
Nussdorfer
Gastone G
GG
Nowak
Krzysztof W
KW
Zyterska
Agnieszka
A
Ziolkowska
Agnieszka
A
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D000077270:Exenatide; D005260:Female; D005934:Glucagon / Q000097:blood; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D008112:Liver Glycogen / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage; D010455:Peptides / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000819:agonists / Q000037:antagonists & inhibitors; D014688:Venoms / Q000008:administration & dosage*
D001786:Blood Glucose; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D020738:Leptin; D008112:Liver Glycogen; D010446:Peptide Fragments; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C083773:exendin (9-39); D005934:Glucagon; D000077270:Exenatide