AbstractIn Type-2 diabetes, the classic biguanide and sulphonylurea drugs remain first line treatments for alleviating chronic insulin resistance and hyperglycaemia. However, newly emerging DPP-4 enzyme inhibitors or long acting hormone-based therapeutics provide second line alternatives. The discovery of novel peptide therapeutics for the treatment of diabetes and obesity offers simultaneously targeting of multiple molecular pathways. Peptide-based therapies provide highly specific mechanisms for controlling multiple aspects of glucose dysregulation including improving post-prandial glycaemia, satiety and gastric emptying. Dietary proteins must first be hydrolysed to unlock their bioactive peptide components. Investigating the oral efficacy of marine protein hydrolysates was a key aim of this research. Initial screening, using BRIN-BD11, GLUTag and STC-1 cell lines, enabled bioactivities to be identified from a variety of biological protein sources. Generally, hydrolysates generated using multiple proteolytic enzymes, provided a more effective strategy for enhancing insulin, GLP-1 and GIP secretion from cultured cells. The bioactivity blue whiting, boarfish, salmon and Palmaria palmata derived peptides varied significantly, interestingly, even when identical enzyme hydrolysis methods were used. Hydrolysates administered orally at 50-150 mg/kg/bw led to an improvement in post-prandial glycaemia and insulinotropic responses in normal mice, but unfortunately in some instances were less effective at reducing food intake and promoting satiety. Long-term oral administration of Palmaria palmata, boarfish and salmon skin hydrolysates resulted in improved non-fasting glucose, plasma lipids and terminal glycated haemoglobin in ob/ob or Streptozotocin diabetes induced mouse models. Finally, within a double blind placebo controlled crossover trial, glucose tolerance in healthy individuals had resulted in no improvement in post-prandial glucose excursion using 3.5g of boarfish protein hydrolysate, of which had previously shown the most promising in vitro and in vivo results. Future study will need to assess the quantity of protein hydrolysate required for humans aiming to present the same positive effects seen within the cell and animal study models.
|Date of Award||Nov 2018|
|Sponsors||Science Foundation Ireland & DEL|
|Supervisor||Finbarr O'Harte (Supervisor) & Philip Allsopp (Supervisor)|
Exploring the antidiabetic potential of protein hydrolysates derived from underutilized marine sources
McLaughlin, C. (Author). Nov 2018
Student thesis: Doctoral Thesis