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

Open access

Abstract

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Gautier-Stein A, Mithieux G. A role for PYY3–36 in GLP1-induced insulin secretion. Mol Metab 2, 123–125, 2013.

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.

Girisha BS, Viswanathan N. Comparison of cutaneous manifestations of diabetic with nondiabetic patients: A case-control study. Clin Dermatol Rev 1, 9–14, 2017.

Ghosh S. Ectopic fat: The potential target for obesity management. J Obes Metab Res 1, 30–38, 2014.

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

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.

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.

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

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.

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.

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.

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.

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.

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.

Mahmoud AM. Peptide tyrosine tyrosine (PYY) as a new strategy for treating obesity. Al-Azhar Assiut Med J 14, 101–118, 2016.

Mobbs CV. Orphaned no more? Glucose-sensing hypothalamic neurons control insulin secretion. Diabetes 65, 2473–2475, 2016.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

VanGuilder HD, Vrana KE, Freeman WM. Twenty-five years of quantitative PCR for gene expression analysis. Bio-techniques 44, 619–626, 2008.

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.

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.

Zhang W, Cline MA, Gilbert ER. Hypothalamus-adipose tissue crosstalk: neuropeptide Y and the regulation of energy metabolism. Nutr Metab (Lond) 11, 27, 2014.

Journal Information


CiteScore 2018: 1.27

SCImago Journal Rank (SJR) 2018: 0.411
Source Normalized Impact per Paper (SNIP) 2018: 0.441

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 120 120 14
PDF Downloads 105 105 15