<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>The incretin hormones glucagon-like peptide-1 (GLP-1)
and glucose-dependent insulinotropic polypeptide (GIP)
are important in blood glucose regulation.However, both incretin
hormones are rapidly degraded by the enzyme dipeptidyl
peptidase IV (DPPIV). The concept of DPPIV inhibition
as a treatment for type 2 diabetes was evaluated in a new
large animal model of insulin-deficient diabetes and reduced
<italic>β</italic>-cell mass, the nicotinamide (NIA) (67 mg/kg) and streptozotocin
(STZ) (125 mg/kg)–treated minipig, using the
DPPIV inhibitor, valine pyrrolidide (VP) (50 mg/kg).VP did
not significantly affect levels of intact GLP-1 but increased
levels of intact GIP (from 4543 ± 1880 to 9208 ± 3267 pM
× min; <italic>P</italic>&lt;.01), thus improving glucose tolerance (area under
the curve [AUC] for glucose reduced from 1904 ± 480 to
1582 ± 353 mM × min;<italic>P</italic> = .05).VP did not increase insulin
levels during the oral glucose tolerance test (OGTT) but increased
the insulinogenic index in normal animals (from 83 ± 42 to 192 ± 108; <italic>P</italic> &lt; .05), but not after NIA + STZ,
possibly because of less residual insulin secretory capacity
in these animals. GIP seems to contribute to the antihyperglycemic
effect of VP in this model; however, additional
mechanisms for the effect of DPPIV inhibition cannot be
excluded. The authors conclude that DPPIV inhibitors may
be useful to treat type 2 diabetes, even when this is due to
reduced <italic>β</italic>-cell mass.</p>
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Exp Diabesity Res. 2003; 4(2):93-105