Effects of Inhibiting Dipeptidyl Peptidase-4 (DPP4) in Cows with Subclinical Ketosis

Abstract

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.

Haematological, clinical–chemical and immunological consequences of feeding Fusarium toxin contaminated diets to early lactating dairy cows

“…Thus, early lactating cows seem to be in an immunologically more dysregulated T cell balance compared to later stages of lactation. This finding is in general agreement with recent findings in transition cows (Schulz et al 2015, Tienken et al 2015) but contrasts another experiment where time and treatment (body condition score, monensin, essential oils) around calving influenced the CD4+/CD8+ ratio in an interactive manner (Drong et al 2016). A successive increase in dietary energy concentration resulted in a significant decrease of the CD4+/CD8+ ratio from 2.5 to 2.1 in non-gravid and non-lactating cows (Dänicke et al 2016).…”

Novel Antidiabetic Agents and Their Effects on Lipid Profile: A Single Shot for Several Cardiovascular Targets

“…reported similar results in high-fat-fed animals, including reduction in plasma non-esterified fatty acids, after 14 weeks of treatment with evo-gliptin [ 114 ]. Moreover, a study conducted in cows showed how the use of DPP4i was related to reduced non-esterified fatty acids and triglycerides levels [ 115 ]. In addition, sitagliptin reduced intestinal cholesterol absorption in obese insulin-resistant mice, suggesting another potential mechanism translating into improved cholesterol metabolism [ 116 ].…”

Different milk feeding intensities during the first 4 weeks of rearing dairy calves: Part 2: Effects on the metabolic and endocrine status during calfhood and around the first lactation

“…Hormone Analyses. For trial 1, RIA was used for determining the insulin concentrations (IM3210, Insulin IRMA KIT, Immunotech, Beckman Coulter, Brea, CA) as described previously (Schulz et al, 2015). The intra-assay coefficient of variation (CV) was 7.6% and the interassay CV was 10.7%; the limit of detection (LOD) was 3.95 µU/mL.…”