The glucagon-like peptide-1 mimetic exenatide has a glucose-dependent insulinotropic
effect, and it is effective in controlling blood glucose (BG) with minimal side effects
in people with type 2 diabetes. Exenatide also delays gastric emptying, increases
satiety, and improves β-cell function. We studied the effect of exenatide on insulin
secretion during euglycemia and hyperglycemia in cats. Nine young, healthy, neutered,
purpose-bred cats were used in a randomized, cross-over design. BG concentrations
during an oral glucose tolerance test were determined in these cats previously. Two
isoglycemic glucose clamps (mimicking the BG concentration during the oral glucose
tolerance test) were performed in each cat on separate days, one without prior treatment
(IGC) and the second with exenatide (1 μg/kg) injected subcutaneously 2 h before (ExIGC).
BG, insulin, and exenatide concentrations were measured, and glucose infusion rates
were recorded and compared in paired tests between the two experiments. After exenatide
injection, insulin serum concentrations increased significantly (2.4-fold; range 1.0-
to 9.2-fold; P = 0.004) within 15 min. This was followed by a mild decrease in BG
concentration and a return of insulin concentration to baseline despite a continuous
increase in serum exenatide concentrations. Insulin area under the curve (AUC) during
ExIGC was significantly higher than insulin AUC during IGC (AUC ratio, 2.0 ± 0.4;
P = 0.03). Total glucose infused was not significantly different between IGC and ExIGC.
Exenatide was detectable in plasma at 15 min after injection. The mean exenatide concentration
peaked at 45 min and then returned to baseline by 75 min. Exenatide was still detectable
in the serum of three of five cats 8 h after injection. No adverse reactions to exenatide
were observed. In conclusion, exenatide affects insulin secretion in cats in a glucose-dependent
manner, similar to its effect in other species. Although this effect was not accompanied
by a greater ability to dispose of an intravenous glucose infusion, other potentially
beneficial effects of exenatide on pancreatic β cells, mainly increasing their proliferation
and survival, should be investigated in cats.
Copyright © 2011 Elsevier Inc. All rights reserved.