Enzymatic Stability and Comparative Effects of Kisspeptin-14, Kisspeptin-13 and Kisspeptin-10 on Beta-Cell Function, Glucose Homeostasis and Appetite Regulation.

Comparative in vitro and in vivo study assessing enzymatic stability and metabolic effects of kisspeptin isoforms

“The current study compared the enzymatic stability and biological effects of kisspeptin-14 (KP-14), kisspeptin-13 (KP-13) and kisspeptin-10 (KP-10) on beta-cell health and function, glucose homeostasis and appetite.”

BRIN-BD11 beta-cells, isolated murine islets, and healthy male and female mice

“Metabolic effects of KP-14, KP-13 and KP-10 were subsequently evaluated in healthy male and female mice.”

In vivo studies used 6 mice per group (3 male, 3 female); in vitro studies used n=3 to n=8 replicates depending on the assay

“Groups of normal homozygous lean (+/+) male (n = 3) and female (n = 3) mice (n = 6 in total per group), originally derived from the colony maintained at Aston University, UK [24], were used at 15–18 weeks of age.”

Acute administration with observations over 180 minutes for food intake and 120 minutes for glucose tolerance

“Indeed, exenatide and KP-10 were associated with distinct reductions (p < 0.01–0.001) in food intake across the full 180 min observation period, although KP-10 was less efficacious (p < 0.01) than exenatide (Figure 5).”

KP-14 was resistant to plasma degradation, while KP-13 and KP-10 underwent N-terminal proteolysis

“KP-14 was resistant to plasma degradation, whereas KP-13 and KP-10 underwent N-terminal proteolysis, with KP-13 degradation generating KP-10 amongst other fragment peptides.”

KP-13 enhanced beta-cell proliferation and protected against cytokine-induced apoptosis, with effects superior to exenatide

“In addition, KP-13 significantly enhanced beta-cell proliferation and protected against cytokine-induced apoptosis, producing superior beta-cell proliferative effects compared to exenatide.”

KP-13 did not impair glucose tolerance, whereas KP-14 and KP-10 did, and all isoforms suppressed food intake

“Acute administration of all kisspeptin peptides elevated circulating glucose concentrations, and while KP-14 and KP-10 impaired glucose tolerance, KP-13 did not.”

Small sample size for in vivo experiments, use of a crossover design, and lack of quantification for KP-10 generation from KP-13 degradation

“In addition, our relatively small sample size for in vivo experiments and the crossover design could also be regarded as limitations in terms of translation.”