Leslie E. Neidert

The serine protease, dipeptidyl peptidase IV as a myokine: dietary protein and exercise mimetics as a stimulus for transcription and release.

Dipeptidyl‐peptidase IV (DPP‐IV) is an enzyme with numerous roles within the body, mostly related to regulating energy metabolism. DPP‐IV is also a myokine, but the stimulus for its release is poorly understood. We investigated the transcription and release of DPP‐IV from skeletal muscle in a three‐part study using C2C12 myotube cultures, an acute rat exercise and postexercise feeding model, and human feeding or human exercise models. When myotubes were presented with leucine only, hydrolyzed whey protein, or chemicals that cause exercise‐related signaling to occur in cell culture, all caused an increase in the mRNA expression of DPP‐IV (1.63 to 18.56 fold change, P < 0.05), but only whey protein caused a significant increase in DPP‐IV activity in the cell culture media. When rats were fed whey protein concentrate immediately following stimulated muscle contractions, DPP‐IV mRNA in both the exercised and nonexercised gastrocnemius muscles significantly increased 2.5‐ to 3.7‐fold (P < 0.05) 3–6 h following the exercise/feeding bout; of note exercise alone or postexercise leucine‐only feeding had no significant effect. In humans, plasma and serum DPP‐IV activities were not altered by the ingestion of whey protein up to 1 h post consumption, after a 10 min bout of vigorous running, or during the completion of three repeated lower body resistance exercise bouts. Our cell culture and rodent data suggest that whey protein increases DPP‐IV mRNA expression and secretion from muscle cells. However, our human data suggest that DPP‐IV is not elevated in the bloodstream following acute whey protein ingestion or exercise.

Plasma dipeptidyl peptidase IV activity and measures of body composition in apparently healthy people

Aim Based on its regulatory action on glucagon-like peptide 1, dipeptidyl peptidase IV (DPP-IV) has increasingly been linked to Type 2 diabetes. However, there is no evidence as to how this normal modulatory enzyme leads to pathology. It is thought that DPP-IV is affected by the development of obesity, which is a common precursor to Type 2 diabetes. Little is known about the relationship between DPP-IV activity in plasma and specific body composition measures. Main methods In the current study, plasma DPP-IV activity and body composition measures were collected from 111 healthy subjects between the ages of 19 and 70 years old for analysis. Key findings The mean plasma DPP-IV activity was 35.9U/L ± 12.3, falling within normal reference value range presented by Durinx et al. DPP-IV activity was negatively correlated with absolute body fat mass, but absolute lean mass was positively correlated. Consistent with the findings, DPP-IV activity was also negatively correlated with absolute gynoid fat (p = 0.0047). DPP-IV activity did not have a significant correlation with absolute android fat mass, visceral adipose tissue, BMI, and age. Significance From these results, it can be concluded that high activity of DPP-IV is not indicative of pathology, and specific body composition components may influence soluble DPP-IV activity in the blood.

Post-exercise Glucose Response Following Whey Protein Ingestion in Healthy Young People: A Randomized Pilot Study

Methods: Twenty-four participants were randomly assigned to one of three supplementation conditions (CTL: water, WPI: 31g whey protein isolate, and CHO: 32g fructose beverage; WPI and CHO beverages were isocaloric). During the Baseline Visit, participants performed an Oral Glucose Tolerance Test (OGTT) with no exercise or supplementation. On their second and third visits, participants consumed their assigned beverage then completed a maximal treadmill protocol until volitional fatigue. An OGTT was completed on the second visit, and blood samples were collected via venipuncture on the third visit for IL-6, Insulin and DPP-IV.

Endogenous dipeptidyl peptidase IV modulates skeletal muscle arteriolar diameter in rats

The purpose of this study is to investigate that dipeptidyl peptidase IV (DPP‐IV) released from skeletal and vascular smooth muscle can increase arteriolar diameter in a skeletal muscle vascular bed by reducing neuropeptide Y (NPY)‐mediated vasoconstriction. We hypothesized that the effect of myokine DPP‐IV would be greatest in the smallest and least in the largest arterioles. Eight male Sprague Dawley rats (age 7–9 weeks; mass, mean ± SD: 258 ± 41 g) were anesthetized and the gluteus maximus dissected in situ for intravital microscopy analysis of arteriolar diameter of the vascular network. Computational modeling was performed on the diameter measurements to evaluate the overall impact of diameter changes on network resistance and flow distribution. In the first set of experiments, whey protein isolate powder was added to physiological saline solution, put in a heated reservoir, and applied to the preparation to induce release of DPP‐IV from the muscle. This resulted in an order‐dependent increase in arteriolar diameter, with the largest change in the 6A arterioles (63% more reactive than 1A arterioles; P < 0.05). This effect was abolished by adding the DPP‐IV inhibitor, Diprotin A. To test if the DPP‐IV released was affecting NPY‐mediated vasoconstriction, we applied NPY and whey protein, which resulted in attenuated vasoconstriction. These findings suggest that DPP‐IV is released from muscle and has a unique effect on blood flow, which appears to act on NPY to attenuate vasoconstriction. The findings suggest that DPP‐IV released from the skeletal or smooth muscle can alter muscle blood flow.