Fish skin gelatin hydrolysates as dipeptidyl peptidase IV inhibitors and glucagon-like peptide-1 stimulators improve glycaemic control in diabetic rats: A comparison between warm- and cold-water fish

• Warm-water fish skin gelatin contains high amounts of imino acids.
• Warm-water fish skin gelatin hydrolysates have great DPP-IV inhibitory activity.
• Six isolated peptides comprised Pro as the second N-terminal residue.
• HSGH and TSGH inhibited plasma DPP-IV activity and induced GLP-1 secretion.
• TSGH improved the glycaemic control better than HSGH in diabetic rats.
• The protein with high imino acid content had the potential to improve diabetes.

Various warm- and cold-water fish skins were used to prepare gelatin hydrolysates and compare their in vitro dipeptidyl peptidase IV (DPP-IV) inhibitory activity. The DPP-IV inhibitory activity of gelatin hydrolysates from warm-water fish was greater than that from cold-water fish. The <1.5 kDa ultrafiltration fractions obtained from halibut skin hydrolysate (HSGH) and tilapia skin gelatin hydrolysate (TSGH) displayed in vitro DPP-IV inhibitory activity of 38.2 and 51.9% at a sample concentration of 1 mg solid/mL, respectively, and they were used for in vivo antihyperglycaemic experiment. The daily administration of TSGH for 30 days was more potent to improve the glucose tolerance in streptozotocin-induced diabetic rats than that of HSGH due to the inhibition of plasma DPP-IV activity, enhancement of glucagon-like peptide-1 (GLP-1) and insulin secretion. Therefore, the warm-water fish skin gelatin, rich in imino acids, has the potential to be the precursor of DPP-IV inhibitor for improvement of diabetes.