Beneficial effects of tigerinin-1R on glucose homeostasis and beta cell function in mice with diet-induced obesity-diabetes

• Tigerinin-1R is resistant to in vitro degradation by plasma enzymes.
• Tigerinin-1R improved glucose tolerance in high-fat fed mice.
• Tigerinin-1R improved secretory functions of islets isolated from treated mice.

AimsThis paper investigates the anti-diabetic effects of tigerinin-1R (RVCSAIPLPICH.NH2), a previously described amphibian host defence peptide, in mice with diet-induced obesity-diabetes.MethodsProteolytic degradation of synthetic tigerinin-1R was investigated by reversed-phase HPLC and MALDI-TOF mass spectrometry. Changes in glycaemic responses and metabolic parameters were measured in mice with high fat diet-induced obesity-diabetes treated with twice-daily with of tigerinin-1R (75 nmol/kg bw) for 15 days. Indirect calorimetry and body composition were measured by CLAMS and DEXA whole body scanning. Insulin secretory responses of islets isolated from treated and untreated mice were examined.ResultsTigerinin-1R was resistant to in vitro degradation by plasma enzymes. Twice-daily injection of tigerinin-1R for 15 days had no significant effect on food intake or body weight. Non-fasting glucose levels were significantly lowered, and insulin levels were elevated compared to saline treated controls. Glycaemic responses to both oral and intraperitoneal glucose administration were significantly improved by tigerinin-1R treatment. Plasma insulin was also significantly elevated. The peptide had no significant effect on insulin sensitivity but the beta cell responses of islets isolated from treated mice to a range of nutrients and peptidergic secretagogues were significantly improved. Oxygen consumption, CO2 production, respiratory exchange ratio, energy expenditure and body composition were not significantly altered by treatment with tigerinin-1R.ConclusionTigerinin-1R significantly improves glucose homeostasis and may have potential as a novel antidiabetic agent.