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New approaches to treatment of feline diabetes mellitus

Final report, Winn grant W09-015
The incretin effect: A potential role for GLP-1 analogues in the treatment of feline diabetes?
Investigators: Chen Gilor, Thomas Graves; University of Illinois at Urbana-Champaign
A compelling animal model for diabetes is the cat because cats develop a spontaneous form of diabetes that closely resembles human type 2 diabetes. Incretin hormones are secreted from the intestines in response to specific nutrients. They potentiate insulin secretion and offer beneficial effects of glucose homeostasis. Two incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1), account for the incretin effect in humans. One goal of this study was to determine whether the incretin effect occurs in cats by comparing the effect of oral glucose, lipids, or amino acids on serum concentrations of insulin, GIP, and GLP-1 in 10 healthy cats. The results indicated that the incretin effect does exist in cats but the effect on glucose-dependent insulin secretion is not as substantial as it is in people. They also noted that this potentiated effect is mediated by GLP-1 but not GLP. This lack of GIP response and a weak incretin effect could make the cat relatively glucose intolerant and might lead to inappropriate glycemic control in cats fed a diet high in carbohydrates.
Exenatide is a GLP-1 mimetic drug that has a glucose-dependent insulinotropic effect. In people with type 2 diabetes, exenatide is effective in controlling blood glucose with minimal side effects. The other goal of this study was to evaluate the effect of exenatide on insulin secretion during euglycemia and hyperglycemia in 9 young, healthy cats. The results indicate that exenatide in cats does stimulate glucose-dependent insulin secretion that is similar to the effect of exenatide in people. Further evaluation of the results did not show improved glucose tolerance with exenatide because its duration of effect was too short. The investigators feel that GLP-1-based medications have potential in treatment of diabetes in cats. Though exenatide will most likely not be clinically useful in cats, other drugs with a similar mechanism of action but longer duration of effect may be helpful. Such drugs would likely promote insulin secretion but may be safer than insulin injections because of the reduced likelihood of hypoglycemia. [VT]
Gilor, C., T. K. Graves, et al. (2011). The GLP-1 mimetic exenatide potentiates insulin secretion in healthy cats. Domest Anim Endocrinol 41(1): 42-49.

Gilor, C., T. K. Graves, et al. (2011). The incretin effect in cats: comparison between oral glucose, lipids, and amino acids. Domest Anim Endocrinol 40(4): 205-212.

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