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.
Department of Histology and Embryology, Karol Marcinkowski University of Medical Sciences, PL-60781 Poznan, Poland.
Ludwik K
LK
Malendowicz
Carlo
C
Macchi
Gastone G
GG
Nussdorfer
Krzysztof W
KW
Nowak
Agnieszka
A
Zyterska
Agnieszka
A
Ziolkowska
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