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.
Highlights
Dipeptidyl peptidase-4 (DPP4) plays a major role in glucose metabolism and is responsible for the degradation of incretin hormones, such as glucagon-like peptide-1 (GLP-1)
According to the pharmacokinetics and pharmacodynamics (PK/PD) results, we considered the dosage of 0.3 mg/kg body weight (BW) as most suitable
The results showed that the impact of DPP4 inhibition was less in cows of subclinical ketosis, respectively during early lactation
Summary
Dipeptidyl peptidase-4 (DPP4) plays a major role in glucose metabolism and is responsible for the degradation of incretin hormones, such as glucagon-like peptide-1 (GLP-1). Human GLP1 is released from the small intestine in response to oral glucose [1]. It stimulates insulin secretion via activating specific receptors on the islet β-cells, suppresses glucagon secretion, inhibits gastric emptying and reduces appetite [2]. Chronic elevated concentrations of GLP-1 were shown to result in reduced hepatic fat accumulation and significantly lower TG concentrations in rat and mouse model [3]. After enzymatic degeneration via DPP4, which occurs within minutes following ingestion, only 10–20% of active GLP-1 remains in blood. DPP4 inhibitors are employed in human medicine to prolong the beneficial incretin effects, in particular to improve insulin sensitivity, with the aim to treat type II diabetes [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
