scholarly journals Mesopelagic Fish Protein Hydrolysates and Extracts: A Source of Novel Anti-Hypertensive and Anti-Diabetic Peptides

2021 ◽  
Vol 8 ◽  
Author(s):  
Azza S. Naik ◽  
R. D. Whitaker ◽  
S. Albrektsen ◽  
Runar G. Solstad ◽  
Lars Thoresen ◽  
...  

The abundance of fish and zooplankton (1 × 109 tons to 7 × 1010 tons) in the mesopelagic zone of the ocean is a source of novel raw materials that provides opportunities for sustainable new product development. The peculiar conditions of light and pressure in this ecological zone and the position of the specific organisms in the marine food chain results in diversity in their bio-composition. Mesopelagic fish are an underutilized resource, rich in proteins and omega-3 oils, and present opportunities to develop novel feed, food and functional food ingredients and products. However, there is also a need to ensure that this resource is not overfished and is processed to optimize the catch in line with sustainability goals. There is therefore a need to establish sustainable bioprocessing technologies to yield value added products from mesopelagic fish species. In the present study, various protein extracts from the mesopelagic fish Maurolicus muelleri (M) and Meganyctiphanes norvegica (Northern Krill) (K) and combinations of proteins from these species (C) were generated using hydrolysis methods. Protein Hydrolysates were generated using four different enzymes including Alcalase, endocut-01, endogenous M/K enzymes and FoodPro PNL. Hydrolysates were characterized and assessed for their ability to inhibit enzymes important in diseases associated with metabolic syndrome. The ability of generated Hydrolysates to inhibit enzymes including Angiotensin-1-converting enzyme (ACE-1; EC. 3.4.15.1) associated with blood pressure regulation, Acetylcholinesterase (AChE; EC 3.1.1.7) associated with maintenance of the nervous system, and Dipeptidyl peptidase IV (DPP-IV; EC 3.4.14.5) linked with development of type-2-diabetes, was determined. In a separate process, the same mesopelagic fish species were transformed into fishmeal, Hydrolysates, fish-silage, and aqueous extracts (AQ) and screened for bioactivities using the same bioassays. The Hydrolysates contained greater than 60% protein (dry weight basis) when analyzed using the DUMAS method. A hydrolysate from M. muelleri generated using FoodPro PNL (M1) inhibited the ACE-1 enzyme by 89.56% when assayed at a concentration of 1 mg/ml compared to the positive control Captopril©. Aqueous extract two (AQ2) inhibited ACE-1 by 95.28% when assayed at 1 mg/ml compared to the control. Sample M1 inhibited DPP-IV by 100% and aqueous extract one (AQ1) inhibited the same enzyme by 90.08% when assayed at a concentration of 1 mg/ml compared to Sitagliptin used as the positive control. All samples assayed did not significantly inhibit the enzyme AChE–fraction C3 (combined hydrolzate 3: Krill and M. muelleri) inhibited AChE by 27.48% only. Based on these results samples M1, C3, and AQ1 were selected for further characterization and the IC50 values for each were determined in relation to ACE-1 and DPP-IV inhibition as well as their amino acid composition. Glutamate and aspartate were the most abundant amino acids in the selected samples. IC50 values of <0.2 mg/ml and distinct terminal amino acids were identified in each of the three fractions. The study shows that targeting processing of mesopelagic fish have potential to generate Hydrolysates for use in the prevention of type-2-diabetes and hypertension.

2013 ◽  
Vol 73 (1) ◽  
pp. 34-46 ◽  
Author(s):  
Orla Power ◽  
A. B. Nongonierma ◽  
P. Jakeman ◽  
R. J. FitzGerald

The prevalence of type 2 diabetes mellitus (T2DM) is increasing and it is estimated that by 2030 approximately 366 million people will be diagnosed with this condition. The use of dipeptidyl peptidase IV (DPP-IV) inhibitors is an emerging strategy for the treatment of T2DM. DPP-IV is a ubiquitous aminodipeptidase that cleaves incretins such as glucagon like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), resulting in a loss in their insulinotropic activity. Synthetic DPP-IV drug inhibitors are being used to increase the half-life of the active GLP-1 and GIP. Dietary intervention is accepted as a key component in the prevention and management of T2DM. Therefore, identification of natural food protein-derived DPP-IV inhibitors is desirable. Peptides with DPP-IV inhibitory activity have been identified in a variety of food proteins. This review aims to provide an overview of food protein hydrolysates as a source of the DPP-IV inhibitory peptides with particular focus on milk proteins. In addition, the proposed modes of inhibition and structure–activity relationship of peptide inhibitors are discussed. Milk proteins and associated peptides also display insulinotropic activity and help regulate blood glucose in healthy and diabetic subjects. Therefore, milk protein derived peptide inhibitors may be a unique multifunctional peptide approach for the management of T2DM.


2018 ◽  
Vol 56 (2) ◽  
pp. 187-195 ◽  
Author(s):  
Akinkunmi Paul Okekunle ◽  
Meng Zhang ◽  
Zhen Wang ◽  
Justina Ucheojor Onwuka ◽  
Xiaoyan Wu ◽  
...  

2021 ◽  
Author(s):  
Qian Zhou ◽  
Wan-Wan Sun ◽  
Jia-Cong Chen ◽  
Huilu Zhang ◽  
Jie Liu ◽  
...  

Abstract Although elevated circulating amino acids are associated with the onset of type 2 diabetes (T2D), how amino acids act on cell insulin signaling and glucose uptake remains unclear. Herein, we report that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or overexpressing human phenylalanyl-tRNA synthetase (hFARS) developed insulin resistance and symptoms of T2D. Mechanistically, FARS phenylalanylated lysine 1057/1079 of IRβ (F-K1057/1079) inactivated IRβ and prevented insulin from generating insulin signaling to promote glucose uptake by cells. SIRT1 reversed F-K1057/1079 and counteracted the insulin-inactivating effects of hFARS and phenylalanine. F-K1057/1079 and SIRT1 levels of white cells of T2D patients’ blood samples were positively and negatively correlated with T2D onset, respectively. Blocking F-K1057/1079 with phenylalaninol sensitized insulin signaling and relieved T2D symptoms in hFARS-transgenic and db/db mice. We revealed mechanisms of how phenylalanylation inactivates insulin signaling that may be employed to control T2D.


2020 ◽  
Vol 66 (1) ◽  
pp. 18-36
Author(s):  
Toyin D. Alabi ◽  
Nicole L. Brooks ◽  
Oluwafemi O. Oguntibeju

SummaryIntroduction: The liver is involved in the metabolism of xenobiotics and their metabolites and it is vulnerable to oxidative damage. Hyperglycaemia is highly implicated in the progression of diabetes mellitus, and adversely affects the liver. Though, conventional hypoglycaemic drugs may be effective in reducing blood glucose, they do not appear to be effective in attenuating the progression of diabetes and its complications.Objective: This study evaluated the ameliorative effects of Anchomanes difformis on hyperglycaemia and hepatic injuries in type 2 diabetes.Methods: Type 2 diabetes was induced in male Wistar rats with a single intraperitoneal injection of streptozotocin (40 mg/kg BW) after two weeks of fructose (10%) administration. Aqueous extract of A. difformis (200 and 400 mg/kg BW) and glibenclamide (5 mg/kg BW) were administered orally for six weeks. Blood glucose concentrations were measured. Serum levels of liver dysfunction markers (ALT, AST, and ALP), total cholesterol, triglycerides, HDL- and LDL-cholesterol were investigated. Total protein, albumin, and globulin were also assessed. Antioxidant parameters: ORAC, GSH, GSSG, SOD, CAT and FRAP were evaluated in the liver while ORAC, FRAP and lipid peroxidation were determined in the serum. Histological examination of the liver tissue was carried out.Results: Treatment with aqueous extract of A. difformis significantly (p<0.05) reduced blood glucose and reversed steatosis in the diabetic-treated rats. The antioxidant status of diabetic-treated rats was significantly (p<0.05) improved. Serum levels of liver dysfunction markers were significantly (p<0.05) reduced in diabetic-treated rats.Conclusion: The findings in this study revealed that 400 mg/kgBW Anchomanes difformis was more effective than 200 mg/kg BW in ameliorating diabetes-induced hepatopathy, however, both doses of Anchomanes difformis demonstrated more antidiabetic ability than glibenclamide. Anchomanes difformis may be a novel and potential therapeutic agent in the management of diabetes and resulted hepatic injuries.


2010 ◽  
Vol 89 (3) ◽  
pp. e49-e52 ◽  
Author(s):  
Seung Jin Han ◽  
Hae Jin Kim ◽  
Sung-E Choi ◽  
Yup Kang ◽  
Kwan Woo Lee ◽  
...  

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Yun Zhu ◽  
Jiang He ◽  
Lyle G Best ◽  
Elisa T Lee ◽  
Barbara V Howard ◽  
...  

Background: Type 2 diabetes (T2D) is characterized by profound metabolic abnormalities. Current glycemic indicators have limitations in identifying early metabolic alterations. Objective: To identify novel metabolic predictors of T2D in American Indians participating in the Strong Heart Family Study. Methods: Among 2,129 participants who had normal fasting glucose (NFG) at baseline (2001-2003) and also attended clinical examination after 5-year follow-up (2006-2009), 142 developed incident T2D, 514 developed incident impaired fasting glucose (IFG), and 1,473 remained to be NFG. The current analysis included all incident cases of T2D (n=142), 146 incident IFG (randomly selected from 514 participants with incident IFG) and 144 NFG (randomly selected from 1,473 participants with NFG at both visits). Baseline plasma metabolites were detected by high-resolution LC/MS. The prospective association of each metabolite with risk for T2D or IFG was investigated using weighted Cox’s hazard regression with frailty model, adjusting for sex, study center, age, BMI, renal function, fasting glucose and fasting insulin at baseline. Multiple testing was corrected by Bonferroni correction (significance level 2.8х10-6). Results: Thirty-nine metabolites from several major fuel sources, including sugar amino acids, amino acids, lipids, alkaloids, alkylamines, carboxylic acids, steroids, and aromatic homomonocylic/heteropolycyclic compounds, significantly predicted future risk of T2D (10 metabolites), or IFG (27 metabolites), or both (2 metabolites). Of these, N1,N12-diacetylspermine and betanidin, respectively, were the strongest predictors for increased (HR=4.59, 95% CI, 2.55-8.24, P=3.49х10-7) and decreased risk of T2D (HR=0.38, 95% CI, 0.28-0.52, P=4.64х10-10). The corresponding strongest predictors for IFG were hexanoic acid (HR=2.34, 95% CI, 1.84-2.98, P=3.15х10-12) and l-palmitoylcarnitine (HR=0.26, 95% CI, 0.18-0.37, P=1.14х10-13), respectively. Two metabolites, betanidin and dopamine, significantly predicted future onset of both T2D (HR=0.38, 95% CI, 0.28,0.52, P=4.64х10-10 for betanidin; HR=2.48, 95% CI, 1.71-3.58, P=1.42х10-6 for dopamine) and IFG (HR=0.52, 95% CI, 0.43,0.62, P=1.35х10-12 for betanidin; HR=2.24, 95% CI, 1.73,2.89, P=5.79х10-10 for dopamine). Multiple unknown compounds were also independently associated with risk of T2D, IFG or both. Conclusions: This study identifies both novel and known metabolic alterations associated with risk of diabetes in American Indians, an ethnic group suffering from disproportionately high rates of T2D. The incomplete overlapping of metabolic profiles between T2D and IFG highlights differential metabolic states of diabetes development. Our results not only provide novel insights in disease pathogenesis but also valuable data on potential new targets for risk prediction and treatment.


Sign in / Sign up

Export Citation Format

Share Document