A novel oral form of salmon calcitonin improves glucose homeostasis and reduces body weight in diet-induced obese rats

Aim: To investigate the effects of acute and chronic administration of a novel oral formulation of salmon calcitonin (sCT) on glycaemic control, glucose homeostasis and body weight regulation in diet-induced obese (DIO) rats-an animal model of obesity-related insulin resistance and type 2 diabetes. Methods: DIO rats were acutely given a single dose of oral sCT (0.5 and 2 mg/kg), its oral vehicle N-(5-chlorosalicyloyl)-8-aminocaprylic acid (5-CNAC) or injectable sCT (5 and 10 mu g/kg) (n = 8), followed by oral glucose tolerance test (OGTT). Other DIO rats were chronic treated twice daily with oral vehicle 5-CNAC (n = 6), oral sCT (0.5 and 2 mg/kg) or injectable sCT (10 mu g/kg) (n = 8). Fasting and postprandial glucose and pancreatic hormones, body weight and insulin sensitivity were assessed. Results: A single dose of oral sCT acutely reduced glucose and insulin area under the curve during OGTT by approximately 65 and 85%, respectively, compared with vehicle (p < 0.001). Chronic treatment with oral sCT significantly reduced both fasting and postprandial glucose and insulin levels by approximately 1.5 mM and 65%, respectively, compared with vehicle. Oral sCT concomitantly improved insulin sensitivity (homeostatic model assessment, HOMA). In contrast, injectable sCT resembling higher systemic exposure did not improve glycaemic control, either acutely or during chronic treatment. Furthermore, both oral and injectable sCT reduced body weight by 15% compared with vehicle (p < 0.05). Conclusion: A novel oral form of sCT showed antidiabetic effects in DIO rats by improving glycaemic control, glucose homeostasis, insulin sensitivity and body weight.