TY - JOUR
T1 - The frog skin host-defense peptide CPF-SE1 improves glucose tolerance, insulin sensitivity and islet function and decreases plasma lipids in high-fat fed mice
AU - Srinivasan, Dinesh
AU - Ojo, Opeolu O.
AU - Owolabi, Bosede O.
AU - Conlon, J. Michael
AU - Flatt, Peter R.
AU - Abdel-Wahab, Yasser H.A.
N1 - Funding Information:
Funding for this study was provided by a project Grant from Diabetes UK (Grant number 12/0004457 ) and an award of a University Vise Chancellor Research Studentship to DKS.
Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/7/7
Y1 - 2015/7/7
N2 - Abstract The frog skin host-defense peptide CPF-SE1 has previously been shown to stimulate the in vitro release of insulin from clonal BRIN-BD11 β-cells. In this study, the in vivo effects of the peptide were investigated in male NIH Swiss mice maintained on a high-fat diet to induce obesity and insulin resistance. Insulin-secretory responses of islets isolated from treated and untreated mice and changes in islet morphology were also examined. Total body fat, plasma glucagon, triglyceride and cholesterol concentrations were measured at the end of the treatment period. Acute intraperitoneal administration of CPF-SE1 (75 nmol body weight) to high-fat fed mice together with glucose (18 mmol/kg body weight) improved glucose tolerance and insulin responses compared to high-fat fed controls. Long term administration of CPF-SE1 (twice-daily administration of 75 nmol/kg body weight for 28 days) did not affect body weight or energy intake but decreased circulating glucose and increased insulin concentrations. Insulin sensitivity and insulin-secretory responses of islets to secretagogues were also significantly improved at 28 days in peptide-treated mice. In addition, significant decreases in plasma glucagon concentrations, pancreatic insulin and glucagon content, islet and beta cell area, body fat and plasma triglyceride levels were observed in CPF-SE1 treated with mice. In conclusion, CPF-SE1 improves beta cell function, insulin sensitivity and glycaemic control whilst reducing total body fat and circulating triglyceride levels. The peptide shows potential for development into an agent for treatment of patients with metabolic syndrome and type 2 diabetes.
AB - Abstract The frog skin host-defense peptide CPF-SE1 has previously been shown to stimulate the in vitro release of insulin from clonal BRIN-BD11 β-cells. In this study, the in vivo effects of the peptide were investigated in male NIH Swiss mice maintained on a high-fat diet to induce obesity and insulin resistance. Insulin-secretory responses of islets isolated from treated and untreated mice and changes in islet morphology were also examined. Total body fat, plasma glucagon, triglyceride and cholesterol concentrations were measured at the end of the treatment period. Acute intraperitoneal administration of CPF-SE1 (75 nmol body weight) to high-fat fed mice together with glucose (18 mmol/kg body weight) improved glucose tolerance and insulin responses compared to high-fat fed controls. Long term administration of CPF-SE1 (twice-daily administration of 75 nmol/kg body weight for 28 days) did not affect body weight or energy intake but decreased circulating glucose and increased insulin concentrations. Insulin sensitivity and insulin-secretory responses of islets to secretagogues were also significantly improved at 28 days in peptide-treated mice. In addition, significant decreases in plasma glucagon concentrations, pancreatic insulin and glucagon content, islet and beta cell area, body fat and plasma triglyceride levels were observed in CPF-SE1 treated with mice. In conclusion, CPF-SE1 improves beta cell function, insulin sensitivity and glycaemic control whilst reducing total body fat and circulating triglyceride levels. The peptide shows potential for development into an agent for treatment of patients with metabolic syndrome and type 2 diabetes.
KW - Amphibian skin peptide
KW - CPF-SE1
KW - Insulin sensitivity
KW - Insulin-release
KW - Metabolic syndrome
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=84935417266&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84935417266&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2015.06.042
DO - 10.1016/j.ejphar.2015.06.042
M3 - Article
C2 - 26123844
AN - SCOPUS:84935417266
SN - 0014-2999
VL - 764
SP - 38
EP - 47
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
M1 - 70077
ER -