1. bookVolume 53 (2019): Issue 1 (January 2019)
Journal Details
First Published
30 Mar 2016
Publication timeframe
4 times per year
access type Open Access

The effect of peptide tyrosine tyrosine (PYY3–36), a selective Y2 receptor agonist on streptozotocin-induced diabetes in albino rats

Published Online: 23 Feb 2019
Volume & Issue: Volume 53 (2019) - Issue 1 (January 2019)
Page range: 26 - 33
Journal Details
First Published
30 Mar 2016
Publication timeframe
4 times per year

Objective. The aim of the present study was to assess the effect of the PYY3–36, as a potential therapy for the type 2 diabetes mellitus (T2DM), induced by high fat diet (HFD) and an intraperitoneal (i.p.) administration of streptozotocin (STZ) in albino rats.

Methods. Forty adult male albino Wistar rats were divided into: 1) control group (C, in which the rats were fed with a standard diet and received vehicle; 2) diabetic group (D, in which T2DM was induced by feeding the rats with HFD for four weeks followed by a single i.p. injection of 35 mg/kg STZ, this group was also allowed to have HFD till the end of the study; and 3) D+PYY3–36 group (in which the diabetic rats were treated with 50 µg/kg i.p. PYY3–36 twice a day for one week). Food intake, water intake, body weight (b.w.), visceral fat weight (VFW), liver glycogen content, serum levels of glucose, insulin, and interleukin-6 (IL-6), were measured. Homeostatic-model assessment of insulin resistance (HOMA-IR) was estimated. The gene expression of the hypothalamic neuropeptide Y (NPY) and visceral nuclear factor kappa B (NF-κB) were assessed by a reverse transcription polymerase chain reaction (RT-PCR).

Results. The PYY3–36 administration to the diabetic group of rats significantly increased the serum insulin levels and liver glycogen content, decreased the body weight, VFW, food intake, water intake, serum levels of the glucose, IL-6, and HOMA-IR. It also decreased the expression of both the hypothalamic NPY and the visceral fat NF-κB.

Conclusion. With respect to the fact of improved insulin release and enhanced insulin sensitivity (an effect that may be mediated via suppressing accumulation of visceral fat and inflammatory markers), in the rats treated with PYY3–36, the PYY3–36 might be considered for the future as a promising therapeutic tool in T2DM.


Abdalla MM. Central and peripheral control of food intake. Endocr Regul 51, 52–70, 2017.2822202210.1515/enr-2017-000628222022Search in Google Scholar

Acuna-Goycolea C, van den Pol AN. Peptide YY (3–36) inhibits both anorexigenic proopiomelanocortin and orexigenic neuropeptide Y neurons: implications for hypothalamic regulation of energy homeostasis. J Neurosci 25, 10510–10519, 2005.10.1523/JNEUROSCI.2552-05.2005672581716280589Search in Google Scholar

Al-Baldawi HF, Al-Shukri al-Wahab D, Al-Abbassi MG, Khazaal FAK. Effect of Bromocriptine on peptide YY and prolactin hormones in Iraqi obese women. Int J Pharm Sci Rev Res 44, 259–264, 2017.Search in Google Scholar

Bobronnikova L. Galectin-3 as a potential biomarker of metabolic disorders and cardiovascular remodeling in patients with hypertension and type 2 diabetes. Vessel Plus 1, 61–70, 2017.10.20517/2574-1209.2016.10Search in Google Scholar

Dabelea D, Stafford JM, Mayer-Davis EJ, D’Agostino R Jr, Dolan L, Imperatore G, Linder B, Lawrence JM, Marcovina SM, Mottl AK, Black MH, Pop-Busui R, Saydah S, Hamman RF, Pihoker C; SEARCH for Diabetes in Youth Research Group. Association of type 1 diabetes vs type 2 diabetes diagnosed during childhood and adolescence with complications during teenage years and young adulthood. JAMA 317, 825–835, 2017.10.1001/jama.2017.0686548385528245334Search in Google Scholar

Dum E, Furtinger S, Gasser E, Bukovac A, Drexel M, Tasan R, Sperk G. Effective G-protein coupling of Y2 receptors along axonal fiber tracts and its relevance for epilepsy. Neuropeptides 61, 49–55, 2017.2784712810.1016/j.npep.2016.10.00527847128Search in Google Scholar

Castro CA, da Silva KA, Buffo MM, Pinto KNZ, Duarte FO, Nonaka KO, Anibal FF, Duarte ACGO. Experimental type 2 diabetes induction reduces serum vaspin, but not serum omentin, in Wistar rats. Int J Exp Pathol 98, 26–33, 2017.10.1111/iep.12220544785928444853Open DOISearch in Google Scholar

Chandarana K, Gelegen C, Irvine EE, Choudhury AI, Amouyal C, Andreelli F, Withers DJ, Batterham RL. Peripheral activation of the Y2-receptor promotes secretion of GLP-1 and improves glucose tolerance. Mol Metab 2, 142–152, 2013.10.1016/j.molmet.2013.03.001377382424049729Search in Google Scholar

Chao PT, Yang L, Aja S, Moran TH, Bi S. Knockdown of NPY expression in the dorsomedial hypothalamus promotes development of brown adipocytes and prevents diet-induced obesity. Cell Metab 13, 573–583, 2011.2153133910.1016/j.cmet.2011.02.019309316121531339Search in Google Scholar

Chatree S, Churintaraphan M, Nway N, Sitticharoon C. Expression of Y2R mRNA expression in subcutaneous and visceral adipose tissues compared between normal weight and obese female subjects. Siriraj Medical Journal 65, 163–167, 2017.Search in Google Scholar

Gautier-Stein A, Mithieux G. A role for PYY3–36 in GLP1-induced insulin secretion. Mol Metab 2, 123–125, 2013.10.1016/j.molmet.2013.06.002377383424049724Search in Google Scholar

Gelling RW, Morton GJ, Morrison CD, Niswender KD, Myers MG Jr, Rhodes CJ, Schwartz MW. Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes. Cell Metabolism 3, 67–73, 2006.10.1016/j.cmet.2005.11.0131639950616399506Open DOISearch in Google Scholar

Girisha BS, Viswanathan N. Comparison of cutaneous manifestations of diabetic with nondiabetic patients: A case-control study. Clin Dermatol Rev 1, 9–14, 2017.10.4103/2542-551X.196944Search in Google Scholar

Ghosh S. Ectopic fat: The potential target for obesity management. J Obes Metab Res 1, 30–38, 2014.10.4103/2347-9906.123883Search in Google Scholar

Gutierrez-Rodelo C, Roura-Guiberna A, Olivares-Reyes JA. Molecular mechanisms of insulin resistance: An update. Gac Med Mex 153, 197–209, 2017.Search in Google Scholar

Hassan AM, Ibrahim MY, Ibrahim HM, Ragy MM, Ali H. Effect of peptide tyrosine tyrosine (PYY3–36) on high fat diet induced obesity and its metabolic hazards in adult albino rats. MJMR 26, 1–14, 2015.Search in Google Scholar

Hassan AM, Jain P, Mayerhofer R, Frohlich EE, Farzi A, Reichmann F, Herzog H, Holzer P. Visceral hyperalgesia caused by peptide YY deletion and Y2 receptor antagonism. Sci Rep 7, 40968, 2017.10.1038/srep40968524770228106168Search in Google Scholar

Ibrahim MY, Aziz NM. Effects of monosodium glutamate on some metabolic parameters in adult male albino rats. MJMR 27, 48–59, 2016.Search in Google Scholar

Jiang JM, Sacco SM, Ward WE. Ovariectomy-induced hyperphagia does not modulate bone mineral density or bone strength in rats. J Nutr 138, 2106–2110, 2008.10.3945/jn.108.09378118936205Search in Google Scholar

Khan D, Vasu S, Moffett RC, Irwin N, Flatt PR. Islet distribution of peptide YY and its regulatory role in primary mouse islets and immortalised rodent and human beta-cell function and survival. Mol Cell Endocrinol 436, 102–13, 2016.10.1016/j.mce.2016.07.02027465830Search in Google Scholar

Li L, de La Serre CB, Zhang N, Yang L, Li H, Bi S. Knockdown of neuropeptide Y in the dorsomedial hypothalamus promotes hepatic insulin sensitivity in male rats. Endocrinology 157, 4842–4852, 2016.10.1210/en.2016-1662513334327805869Search in Google Scholar

Litvinova L, Atochin D, Vasilenko M, Fattakhov N, Zatolokin P, Vaysbeyn I, Kirienkova E. Role of adiponectin and proinflammatory gene expression in adipose tissue chronic inflammation in women with metabolic syndrome. Diabetol Metab Syndr 6, 137, 2014.2551677210.1186/1758-5996-6-137426714525516772Search in Google Scholar

Loh K, Zhang L, Brandon A, Wang Q, Begg D, Qi Y, Fu M, Kulkarni R, Teo J, Baldock P, Bruning JC, Cooney G, Neely GG, Herzog H. Insulin controls food intake and energy balance via NPY neurons. Mol Metab 6, 574–584, 2017.10.1016/j.molmet.2017.03.013544409528580287Search in Google Scholar

Long M, Zhou J, Li D, Zheng L, Xu Z, Zhou S. Long-term over-expression of neuropeptide Y in hypothalamic paraventricular nucleus contributes to adipose tissue insulin resistance partly via the Y5 receptor. PLoS One 10, e0126714, 2015.10.1371/journal.pone.0126714443637725993471Search in Google Scholar

Mahmoud AM. Peptide tyrosine tyrosine (PYY) as a new strategy for treating obesity. Al-Azhar Assiut Med J 14, 101–118, 2016.10.4103/1687-1693.200146Search in Google Scholar

Mobbs CV. Orphaned no more? Glucose-sensing hypothalamic neurons control insulin secretion. Diabetes 65, 2473–2475, 2016.10.2337/dbi16-002727555573Open DOISearch in Google Scholar

Nagarchi K, Ahmed S, Sabus A, Saheb S. Effect of Streptozotocin on Glucose levels in Albino Wister Rats. J Pharm Sci 7, 67–69, 2015.Search in Google Scholar

National Institutes of Health. Institutional Animal Care and Use Committee Guidebook, NIH Publication no. 92-3415. Washington, D.C.: U.S. Government Printing Office. NAL call number: HV 4764, I58 1992, 1992.Search in Google Scholar

Nishizawa N, Niida A, Adachi Y, Masuda Y, Kumano S, Yokoyama K, Asakawa T, Hirabayashi H, Amano N, Takekawa S, Ohtaki T, Asami T. Potent antiobesity effect of a short-length peptide YY-analogue continuously administered in mice. Bioorg Med Chem Lett 27, 3829–3832, 2017a.10.1016/j.bmcl.2017.06.05528684122Open DOISearch in Google Scholar

Nishizawa N, Niida A, Masuda Y, Kumano S, Yokoyama K, Hirabayashi H, Amano N, Ohtaki T, Asami T. Antiobesity effect of a short-length peptide YY analogue after continuous administration in mice. ACS Med Chem-Lett 8, 628–631, 2017b.10.1021/acsmedchemlett.7b00047546719028626523Search in Google Scholar

Panigrahi G, Panda C, Patra A. Extract of Sesbania grandiflora ameliorates hyperglycemia in high fat diet-streptozotocin induced experimental diabetes mellitus. Scientifica (Cairo) 2016, 4083568, 2016.10.1155/2016/4083568489344727313954Search in Google Scholar

Pari L, Chandramohan R. Modulatory effects of naringin on hepatic key enzymes of carbohydrate metabolism in high-fat diet/low-dose streptozotocin-induced diabetes in rats. Gen Physiol Biophys 36, 343–352. 2017.2863561110.4149/gpb_201605528635611Search in Google Scholar

Park S, Fujishita C, Komatsu T, Kim SE, Chiba T, Mori R, Shimokawa I. NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism. FASEB J 28, 5337–5348, 2014.2520574310.1096/fj.14-25838425205743Search in Google Scholar

Park S, Komatsu T, Kim SE, Tanaka K, Hayashi H, Mori R, Shimokawa I. Neuropeptide Y resists excess loss of fat by lipolysis in calorie-restricted mice: a trait potential for the life-extending effect of calorie restriction. Aging Cell 16, 339–348, 2017.10.1111/acel.1255828101970533453828101970Open DOISearch in Google Scholar

Prinz P, Stengel A. Control of food intake by gastrointestinal peptides: Mechanisms of action and possible modulation in the treatment of obesity. J Neurogastroenterol Motil 23, 180–196, 2017.2809652210.5056/jnm16194538311328096522Search in Google Scholar

Ramracheya RD, McCulloch LJ, Clark A, Wiggins D, Johannessen H, Olsen MK, Cai X, Zhao CM, Chen D, Rorsman P. PYY-dependent restoration of impaired insulin and glucagon secretion in type 2 diabetes following rouxen-Y gastric bypass surgery. Cell Rep 15, 944–950, 2016.10.1016/j.celrep.2016.03.091506395227117413Open DOISearch in Google Scholar

Robinson K, Vona-Davis L, Riggs D, Jackson B, McFadden D. Peptide YY attenuates STAT1 and STAT3 activation induced by TNF-alpha in acinar cell line AR42J. J Am Coll Surg 202, 788–796, 2006.10.1016/j.jamcollsurg.2006.01.00716648019Search in Google Scholar

Saleh S, El-Maraghy N, Reda E, Barakat W. Modulation of diabetes and dyslipidemia in diabetic insulin-resistant rats by mangiferin: role of adiponectin and TNF-α. An Acad Bras Cienc 86, 1935–1948, 2014.10.1590/0001-376520142014021225590730Open DOISearch in Google Scholar

Shpakov AO, Derkach KV, Berstein LM. Brain signaling systems in the Type 2 diabetes and metabolic syndrome: promising target to treat and prevent these diseases. Future Sci OA, 1, FSO25, 2015.10.4155/fso.15.23513785628031898Search in Google Scholar

Tan TM, Salem V, Troke RC, Alsafi A, Field BC, De Silva A, Misra S, Baynes KC, Donaldson M, Minnion J, Ghatei MA, Godsland IF, Bloom SR. Combination of peptide YY3–36 with GLP-1(7–36) amide causes an increase in first-phase insulin secretion after IV glucose. J Clin Endocrinol Metab 99, E2317–E2324, 2014.10.1210/jc.2014-2143425860425144632Search in Google Scholar

Torang S, Bojsen-Moller KN, Svane MS, Hartmann B, Rosenkilde MM, Madsbad S, Holst JJ. In vivo and in vitro degradation of Peptide YY3–36 to inactive peptide YY3–34 in humans. Am J Physiol Regul Integr Comp Physiol 310, R866–R874, 2016.10.1152/ajpregu.00394.2015500077626818056Search in Google Scholar

Tourniaire F, Romier-Crouzet B, Lee JH, Marcotorchino J, Gouranton E, Salles J, Walrand S. Chemokine expression in inflamed adipose tissue is mainly mediated by NF-κB. PLoS One 8, e66515, 2013.2382468510.1371/journal.pone.0066515368892823824685Search in Google Scholar

van den Hoek AM, Heijboer AC, Voshol PJ, Havekes LM, Romijn JA, Corssmit EP, Pijl H. Chronic PYY3–36 treatment promotes fat oxidation and ameliorates insulin resistance in C57BL6 mice. Am J Physiol Endocrinol Metab 292, E238–E245, 2007.10.1152/ajpendo.00239.200616940471Search in Google Scholar

VanGuilder HD, Vrana KE, Freeman WM. Twenty-five years of quantitative PCR for gene expression analysis. Bio-techniques 44, 619–626, 2008.10.2144/00011277618474036Search in Google Scholar

Yada T, Dezaki K, Sone H, Koizumi M, Damdindorj B, Nakata M, Kakei M. Ghrelin regulates insulin release and glycemia: physiological role and therapeutic potential. Curr Diabetes Rev 4, 18–23, 2008.10.2174/15733990878350235218220691Search in Google Scholar

Ye H, Yang Z, Li H, Gao Z. NPY binds with heme to form a NPY-heme complex: enhancing peroxidase activity in free heme and promoting NPY nitration and inactivation. Dalton Trans 46, 10315–10323, 2017.10.1039/C7DT01822C28737807Search in Google Scholar

Zhang W, Cline MA, Gilbert ER. Hypothalamus-adipose tissue crosstalk: neuropeptide Y and the regulation of energy metabolism. Nutr Metab (Lond) 11, 27, 2014.10.1186/1743-7075-11-27406628424959194Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo