The inhibition of dipeptidyl peptidase-4 (DPP4) via specific inhibitors is known to result in improved
glucose tolerance and
insulin sensitivity and decreased accumulation of hepatic fat in type II diabetic human patients. The metabolic situation of dairy cows can easily be compared to the status of human diabetes and non-
alcoholic fatty liver. For both,
insulin sensitivity is reduced, while hepatic fat accumulation increases, characterized by high levels of non-
esterified fatty acids (
NEFA) and
ketone bodies.Therefore, in the present study, a
DPP4 inhibitor was employed (BI 14332) for the first time in cows. In a first investigation BI 14332 treatment (
intravenous injection at dosages of up to 3 mg/kg
body weight) was well tolerated in healthy lactating pluriparous cows (n = 6) with a significant inhibition of DPP4 in plasma and liver. Further testing included primi- and pluriparous lactating cows suffering from subclinical
ketosis (β-hydroxybutyrate concentrations in serum > 1.2 mM; n = 12). The intension was to offer effects of DPP4 inhibition during comprehensive lipomobilisation and hepatosteatosis. The cows of subclinical
ketosis were evenly allocated to either the treatment group (daily
injections, 0.3 mg BI 14332/kg
body weight, 7 days) or the control group. Under condition of subclinical
ketosis, the impact of DPP4 inhibition via BI 14332 was less, as in particular β-hydroxybutyrate and the hepatic
lipid content remained unaffected, but
NEFA and
triglyceride concentrations were decreased
after treatment. Owing to lower
NEFA, the revised quantitative
insulin sensitivity check index (
surrogate marker for
insulin sensitivity) increased. Therefore, a positive influence on energy metabolism might be quite possible. Minor impacts on immune-modulating variables were limited to the lymphocyte CD4+/CD8+ ratio for which a trend to decreased values in treated versus control animals was noted. In sum, the DPP4 inhibition in cows did not affect glycaemic control like it is shown in humans, but was able to impact
hyperlipemia, as
NEFA and TG decreased.