Effect of Casein Hydrolysates and Zinc on Insulin Resistance, Renal Function, Pancreatic and Kidney Histopathology in Diabetic Rats
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Abstract
Goat's milk casein hydrolysates combined or not with zinc have interesting nutraceutical properties that limit the multiple complications of type 2 diabetes (T2D). This study aimed to evaluate the effect of goat’s milk casein hydrolysates and zinc (Zn) on insulin resistance, renal function and pancreatic and kidney histopathology, in type 2 diabetic rats (T2D). T2D was induced in rats by high fat diet (HFD) followed by intraperitoneal injection of streptozotocin (35 mg/kg body weight). Diabetic rats (n = 21) were divided into three groups: HFD or HFD combined with casein hydrolysates (HFD-CH) or HFD-CH combined with Zinc (HFD-CH-Zn). The control group (C) fed a standard diet. In high fat diet fed group vs control group HFD vs C, increased glucose levels, Glycated Hemoglobin (HbA1c), Oral Glucose Tolerance Test (OGGT) and Homeostasis model assessment Index-Insulin resistance (HOMA-IR) as well as renal dysfunction were observed while decreased serum insulin levels and Homeostasis model assessment Index-Pancreatic beta cells (HOMA- β ) (p<0.01) was noted. Treatment of diabetic rats with CH and CH-Zn increased insulin levels and HOMA-β index vs HFD group (p<0.01). Both treatments also prevented kidney injury by reducing serum creatinine, urea and uric acid. Histopathological analysis of the pancreas and kidney revealed tissue damages in the HFD vs C. These histological disturbances were reduced by the CH diet associated or not with Zn. Casein hydrolysates when used alone or in combination with zinc showed a beneficial effect on hyperglycaemia and improved renal function and repaired pancreatic and kidney histological damages induced by diabetes.
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References
1. Matboli M, Shafei A, Ali M, Kamal KM, Noah M, Lewis P, Habashy A, Ehab M, Gaber AI, Abedlzaher H. Emerging role of nutrition and the non-coding landscape in type 2 diabetes mellitus: A review of literature. Gene. 2018; 675: 54–61.
2- Cheng F, Han L, Xiao Y, Pan C, Li Y, Ge X, Zhang Y, Yan S, Wang M. D-chiro-inositol ameliorates high fat diet-induced hepatic steatosis and insulin resistance via PKCε-PI3K/AKT pathway. J Agric Food Chem. 2019; 67(21): 5957–5967.
3- Parsamanesh N, Moossavi M, Bahrami A, Butler AE, Sahebkar A. Therapeutic potential of curcumin in diabetic complications. Pharmacol Res. 2018; 136: 181–193.
4- Grossman LD, Roscoe R, Shack AR. Complementary and alternative medicine for diabetes. Can J Diabetes. 2018; 42: S154–61.
5- Aligita W, Muhsinin S, Susilawati E, Dahlia, S. Pratiwi D, Aprilliani D, Artarini A, Adnyana IK. Antidiabetic activity of okra (Abelmoschus
esculentus L) fruit extract. Rasayan J Chem. 2019; 12(1): 157–167. xs
6- Zaky AA, Chen Z, Liu Y, Li S, Jia Y. Preparation and assessment of bioactive extracts having antioxidant activity from rice bran protein hydrolysates. J Food Meas Charact. 2019; 13(4): 2542– 2548.
7- Liu W, Zhou Y, Sun H, Li R, Qin Y, Yu L, Chen Y, Li Y, Tan Y, Zhao R, Zhang W,Jiang S, Xu Y. Goat milk improves glucose homeostasis via enhancement of hepatic and skeletal muscle AMP-activated protein kinase activation and modulation of gut microbiota in streptozocin-induced diabetic rats. Mol Nutr Food Res. 2021; 65(6): e2000888. doi: 10.1002/mnfr.202000888.
8- Murakami M, Hirano T. Intracellular zinc homeostasis and zinc signaling. Cancer Sci. 2008; 99(8): 1515– 1522.
9- Nongonierma AB, FitzGerald RJ. Strategies for the discovery, identification and validation of milk protein-derived bioactive peptides. Trends Food Sci Technol. 2016; 50:26–43.
10- Nongonierma AB , Cadamuro C , Gouic AL , Mudgil P , Maqsood S , FitzGerald RJ, Dipeptidyl peptidase IV (DPP-IV) inhibitory properties of a camel whey protein enriched hydrolysate preparation. Food chem. 2019; 1(279): 70-79.
11- Sultan S, Huma N, Butt MS, Aleem M, Abbas M. Therapeutic potential of dairy bioactive peptides: A contemporary perspective. Crit Rev Food Sci Nutr. 2018; 58(1): 105– 115.
12- Sharma G, Rout PK, Singh G. Characterization of goat milk protein and comparison of milk proteins using polyacrylamide gel electrophoresis. IJSEAS. 2017; 3(4): 13.
13- Zhang Y, Chen R, Ma H, Chen S. Isolation and identification of dipeptidyl peptidase IV-inhibitory peptides from trypsin/chymotrypsin-treated goat milk casein hydrolysates by 2D-TLC and LC–MS/MS. J Agric Food Chem. 2015; 63(40): 8819–8828.
14- Jao CL, Hung CC, Tung YS, Lin PY, Chen MC, Hsu KC. The development of bioactive peptides from dietary proteins as a dipeptidyl peptidase IV inhibitor for the management of type 2 diabetes. Bio Medicine (Taipei). 2015; 5(3): 14.
15- Jou MY, Philipps AF, Lönnerdal B. Maternal zinc deficiency in rats affects growth and glucose metabolism in the offspring by inducing insulin resistance postnatally. J Nutr. 2010; 140(9): 1621–1627.
16- Capdor J, Foster M, Petocz P, Samman S. Zinc and glycemic control: A meta-analysis of randomised placebo controlled supplementation trials in humans. J Trace Elem Med Biol. 2013; 27(2): 137–142.
17- Gembillo G, Visconti L, Giuffrida AE, Labbozzetta V, Peritore L, Lipari A, Calabrese V, Piccoli GB, Torreggiani M, Siligato R, Santoro D. Role of zinc in diabetic Kidney Disease .Nutrients.2022; 14(7): 1353.
18- Derouiche S, Kechrid Z. Zinc supplementation overcomes effects of copper on zinc status, carbohydrate metabolism and some enzyme activities in diabetic and nondiabetic rats. Can J Diabetes. 2016; 40(4): 342–347.
19- Pompano LM, Boy E. Effects of dose and duration of zinc interventions on risk factors for type 2 diabetes and cardiovascular disease: A systematic review and meta-analysis. Adv Nutr. 2021; 12(1): 141–160.
20- Mercier JC, Maubois JL, Poznanski S, Ribadeau-Dumas B. Preparative fractionation of caseins from cattle and sheep by chromatography on D.E.A.E. cellulose using urea and 2-mercaptoethanol. Bull Soc Biol Chem. 1968; 50: 521-530.
21- Adler-Nissen J. Limited enzymatic degradation of proteins: A new approach in the industrial application of hydrolases. J Chem Technol Biotechnol. 1982; 32(1): 138–156.
22- Mat D JL, Cattenoz T, Souchon I, Michon C, Le Feunteun, S. Monitoring protein hydrolysis by pepsin using pH-stat: In vitro gastric digestions in static and dynamic pH conditions. Food Chemistry J (2018); 15 ; 239: 268-275
23- Council of European Communities. Council instructions about the protection of living animals used in scientific investigation. Official J 1987 L 358 of 18-12-1986.
24- Benaicheta N, Labbaci FZ, Bouchenak M, Boukortt FO. Effect of sardine proteins on hyperglycaemia, hyperlipidaemia and lecithin:cholesterol acyltransferase activity, in high-fat diet-induced type 2 diabetic rats. Br J Nutr. 2016; 115(1): 6–13.
25- Kilari BP, Mudgil P, Azimullah S, Bansal N, Ojha S, and Maqsood S. Effect of camel milk protein hydrolysates against hyperglycemia, hyperlipidemia, and associated oxidative stress in streptozotocin (STZ)-induced diabetic rats. J. Dairy Sci. 2020; 104:1–14.
26- Barman S, Srinivasan K. Zinc supplementation alleviates hyperglycemia and associated metabolic abnormalities in streptozotocin-induced diabetic rats. J Physiol Pharmacol. 2016; 570 020: 1-35.
27- Tanaka Y, Mochizuki K, Fukaya N, Shimada M, Goda T. The α-glucosidase inhibitor miglitol suppresses postprandial hyperglycaemia and interleukin-1β and tumour necrosis factor-α gene expression in rat peripheral leucocytes induced by intermittent sucrose loading. Br J Nutr.
2009; 102(2): 221–225.
28- Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia J. 1985; 28(7): 412–419.
29- Gondwe M, Kamadyaapa DR, Tufts M, Chuturgoon AA, Musabayane CT. Sclerocarya birrea [(A. Rich.) Hochst.] [Anacardiaceae] stem-bark ethanolic extract (SBE) modulates blood glucose, glomerular filtration rate (GFR) and mean arterial blood pressure (MAP) of STZ-
induced diabetic rats. Phytomedicine. 2008; 15(9): 699–709.
30- Ismail T, Ahmad Z, Sestili P, Hussain M, Akram K, Ismail A, Akhtar S. Camel’s milk concentrate inhibits streptozotocin induced diabetes. Food Biosci. 2018; 26: 73–79.
31- Tenenbaum M, Bonnefond A, Froguel P, Abderrahmani A. Physiopathology of Diabetes . Rev Francoph Lab. 2018; (502): 26–32.
32- Saeedi PI, Petersohn P, Salpea B, Malanda S, Karuranga N. Unwin S, Colagiuri L, Guariguata A, Motala A, Ogurtsova K. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Research and Clinical Practice. Diabetes Res .Clin. Pract. 2019; 157: 109-119.
33- Foster M, Samman S. Zinc and regulation of inflammatory cytokines: implications for cardio metabolic disease. Nutrients. 2012; 4(7): 676–694.
34- Li YV. Zinc and insulin in pancreatic beta-cells. Endocrine. 2014; 45(2): 178–189.
35- Labbaci FZ, Boukortt FO. Beneficial effects of Algerian green alga Ulva lactuca and its hydroethanolic extract on insulin resistance and cholesterol reverse transport in high-fat/streptozotocin diabetic rats. Prev Nutr Food Sci. 2020; 25(4): 353–361.
36- Liu W, Sun H, Zhou Y, Li Y, Qin Y, Li R, Chen Y, Yu L, Zhao M, Zhang W, Xu Y. Goat milk consumption ameliorates abnormalities in glucose metabolism and enhances hepatic and skeletal muscle AMP-activated protein kinase activation in rats fed with high-fat diets. Mol Nutr Food Res. 2019; 63(24): e1900703.
37- Gong H, Gao J, Wang Y, Luo QW, Guo KR, Ren FZ, Mao XY. Identification of novel peptides from goat milk casein that ameliorate high-glucose-induced insulin resistance in HepG2 cells. J Dairy Sci. 2020; 103(6): 4907–4918.
38- Marquart TJ, Allen RM, Ory DS, Baldán A. miR-33 links SREBP-2 induction to repression of sterol transporters. Proc Natl Acad Sci U S A. 2010; 107(27): 12228–12232.
39- Jia L, Betters JL, Yu L. Niemann-pick C1-like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport. Annu Rev Physiol. 2011; 73(1): 239–259.
40- Oztürk Z, Gurpinar T, Vural K, Boyacıoglu S, Korkmaz M, Var A. Effects of selenium on endothelial dysfunction and metabolic profile in low dose streptozotocin induced diabetic rats fed a high fat diet. Biotech Histochem. 2015; 90(7): 506–515.
41- Magnan C. Lipotoxicité et insulinorésistance. Nutr Clin Métab. 2006; 20(2): 108–113.
42- Selbach Dries S., Da Silveira Soares B., Ziulkoski AL. Oxidative stress in patients with type 2 diabetes mellitus treated with metformin. Scientia Medica. 2017; 27(2): 25857. http://dx.doi.org/10.15448/1980-6108.2017.2.25857.
43- Hurrle S, Hsu WH. The etiology of oxidative stress in insulin resistance. Biomed J. 2017; 40(5): 257–262.
44- Roussel AM. Trace elements (zinc, selenium, chromium, iron), metabolic syndrome, and type 2 diabetes. Med Mal Metab. 2014; 8(5): 489–493.
45- Barman S, Srinivasan K. Attenuation of oxidative stress and cardio protective effects of zinc supplementation in experimental diabetic rats. Br J Nutr. 2017; 117(3): 335–350.
46- Skurikhin E , Pershina O V, Ermakova N N, Ermolaeva L A, Krupin V A, Pakhomova AV, Pan E S, Zeuner MT, Khmelevskaya WDS, Fisenko VP, Mikhaylovich A. J Stem Cell Res Ther, 2018; 8:8.
47- Anton IC, Mititelu-Tartau L, Popa EG, Poroch M, Poroch V, Pelin A-M, Pavel LL, Drochioi IC, Botnariu GE. Zinc chloride enhances the antioxidant status, improving the functional and structural organic disturbances in streptozotocin-induced diabetes in rats. Medicina. 2022;
58(11): 1620.
48- Wang YH, Liu YH, He GR, Lv Y, Du GH. Esculin improves dyslipidemia, inflammation and renal damage in streptozotocin-induced diabetic rats. BMC Complement Altern Med. 2015; 15(1):402.
49- Ziyadeh FN. Mediators of diabetic renal disease: The case for TGF-β as the major mediator. J Am Soc Nephrol. 2004; 15(1): S55–S57.
50- Mason RM, Wahab NA. Extracellular matrix metabolism in diabetic nephropathy. J Am Soc Nephrol. 2003; 14(5): 1358–1373.
51- Lin TA, Wu VC, Wang CY. Autophagy in chronic kidney diseases. Cells. 2019; 8(1): 61.
52- Sen S, Chen S, Feng B, Wu Y, Lui E, Chakrabarti S. Preventive effects of North American ginseng (Panax quinquefolium) on diabetic nephropathy. Phytomedicine. 2012; 19(6): 494–505.
53- Jayaraman R, Subramani S, Sheik Abdullah SH, Udaiyar M. Antihyperglycemic effect of hesperetin, a citrus flavonoid, extenuates hyperglycemia and exploring the potential role in antioxidant and antihyperlipidemic in streptozotocin-induced diabetic rats. Biomed Pharmacother. 2018; 97: 98–106.
54- Thakur N, Chauhan G, Mishra BP, Mendiratta SK, Pattanaik AK, Singh TU, Meshram SK, Mathesh K, Garg L. Comparative evaluation of feeding effects of A1 and A2 cow milk derived casein hydrolysates in diabetic model of rats. J Funct Foods. 2020; 75: 104272.
55- Dixon T., Seeba Z., Abdelgadir Elamin EE., Ahmed Luay OH. Limitations of serum creatinine as a marker of renal function. Sch Acad J Pharm. 2017; 6: 168-170.