Study on the Effect of Peripheral Kisspeptin Administration on Basal and Glucose-induced Insulin Secretion Under Fed and Fasting Conditions in the Adult Male Rhesus Monkey (Macaca mulatta)

Abstract

Kisspeptin (KP)-Kiss1r, a ligand-receptor pair, has recently been implicated as a pivotal regulator of the neuroendocrine reproductive axis. Kiss1 (encoding KP) as well as Kiss1r (encoding receptor for KP) are expressed in several peripheral tissues including the pancreas. But the specific role of KP in the physiology of pancreas is still incompletely deciphered. This study was designed to examine the effect of peripheral KP administration on basal and glucose-induced plasma insulin (an important pancreatic hormone) secretion under fed and fasting conditions in the adult male rhesus monkey. A set of 4 chair-restraint habituated intact adult male rhesus monkeys were assigned to receive intravenous bolus administration of human kisspeptin-10 (KP10, 50 μg), and vehicle (1 ml) in normal fed and fasting conditions without or with glucose infusions. Plasma concentrations of insulin were measured by using a specific IRMA. Glucose infusion significantly stimulated plasma insulin levels (p<0.005). Vehicle administration did not affect both basal and glucose stimulated insulin in fed as well as in fasting condition. KP10 administration had no effect on the basal insulin levels in both fed and fasting as compared to pretreatment or vehicle treatment levels, while it significantly heightened glucose stimulated insulin levels (p<0.05) in both fed and fasted monkeys. The present results show that KP administration does not affect the basal secretion of insulin under both fed and fasting condition while potentiated the glucose-induced insulin levels in the adult male rhesus monkey. Therefore, these findings suggest a potential role of KP in the physiology of pancreas.

Key words

fasting - kisspeptin - kiss1r - insulin - monkey

References

• 1 Oakley AE, Clifton DK, Steiner RA. Kisspeptin signaling in the brain.  Endocr Rev. 2009;  30 713-743
• 2 Tena-Sempere M. GPR54 and Kisspeptin in reproduction.  Hum Reprod Update. 2006;  12 631-639
• 3 Plant TM, Ramaswamy S. Kisspeptin and the regulation of the hypothalamic-pituitary-gonadal axis in the rhesus monkey (Macaca mulatta).  Peptides. 2009;  30 67-75
• 4 Roseweir AK, Millar RP. The role of kisspeptin in the control of gonadotrophin secretion.  Hum Reprod Update. 2009;  15 203-212
• 5 Gottsch ML, Cunningham MJ, Smith JT, Popa SM, Acohido BV, Crowley WF, Seminara S, Clifton DK, Steiner RA. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse.  Endocrinology. 2004;  145 4073-4077
• 6 Irwig MS, Fraley GS, Smith JT, Acohido BV, Popa SM, Cunningham MJ, Gottsch ML, Clifton DK, Steiner RA. Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat.  Neuroendocrinology. 2004;  80 264-272
• 7 Navarro VM, Fernandez-Fernandez R, Castellano JM, Roa J, Mayen A, Barreiro ML, Gaytan F, Aguilar E, Pinilla L, Dieguez C, Tena-Sempere M. Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54.  J Physiol. 2004;  561 379-386
• 8 Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM. Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates.  Proc Natl. Acad Sci USA. 2005;  102 2129-2134
• 9 de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54.  Proc Natl. Acad Sci USA. 2003;  100 10972-10976
• 10 Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno Jr JS, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG, Zahn D, Dixon J, Kaiser UB, Slaugenhaupt SA, Gusella JF, O’Rahilly S, Carlton MB, Crowley Jr WF, Aparicio SA, Colledge WH. The GPR54 gene as a regulator of puberty.  N Engl J Med. 2003;  349 1614-1627
• 11 Teles MG, Bianco SD, Brito VN, Trarbach EB, Kuohung W, Xu S, Seminara SB, Mendonca BB, Kaiser UB, Latronico AC. A GPR54-activating mutation in a patient with central precocious puberty.  N Engl J Med. 2008;  358 709-715
• 12 Matsui H, Takatsu Y, Kumano S, Matsumoto H, Ohtaki T. Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat.  Biochem Biophys Res Commun. 2004;  320 383-388
• 13 Castellano JM, Navarro VM, Fernández-Fernández R, Nogueiras R, Tovar S, Roa J, Vazquez MJ, Vigo E, Casanueva FF, Aguilar E, Pinilla L, Dieguez C, Tena-Sempere M. Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in under nutrition.  Endocrinology. 2005;  146 3917-3925
• 14 Castellano JM, Navarro VM, Fernandez-Fernandez R, Castellano JM, Roa J, Vigo E, Pineda R, Dieguez C, Aguilar E, Pinilla L, Tena Sempere M. Expression of hypothalamic KiSS-1 system and rescue of defective gonadotropic responses by kisspeptin in streptozotocin-induced diabetic male rats.  Diabetes. 2006;  55 2602-2610
• 15 Luque RM, Kineman RD, Tena-Sempere M. Regulation of hypothalamic expression of KiSS-1 and GPR54 genes by metabolic factors: Analyses using mouse models and a cell line.  Endocrinology. 2007;  148 4601-4611
• 16 Yamada S, Uenoyama Y, Kinoshita M, Iwata K, Takase K, Matsui H, Adachi S, Inoue K, Maeda KI, Tsukamura H. Inhibition of metastin (kisspeptin-54)-GPR54 signaling in the arcuate nucleus-median eminence region during lactation in rats.  Endocrinology. 2007;  148 2226-2232
• 17 Wahab F, Aziz F, Irfan S, Zaman W, Shahab M. Short-term fasting attenuates the response of the HPG axis to kisspeptin challenge in the adult male rhesus monkey (Macaca mulatta).  Life Sci. 2008;  83 633-637
• 18 Hauge-Evans AC, Richardson CC, Milne HM, Christie MR, Persaud SJ, Jones PM. A role for kisspeptin in islet function.  Diabetologia. 2006;  49 2131-2135
• 19 Suckale J, Solimena M. Pancreas islets in metabolic signaling--focus on the beta-cell.  Front Biosci. 2008;  13 7156-7171
• 20 Silvestre RA, Egido EM, Hernández R, Marco J. Kisspeptin-13 inhibits insulin secretion without affecting glucagon or somatostatin release: study in the perfused rat pancreas.  J Endocrinol. 2008;  196 283-290
• 21 Bowe JE, King AJ, Kinsey-Jones JS, Foot VL, Li XF, O'Byrne KT, Persaud SJ, Jones PM. Kisspeptin stimulation of insulin secretion: mechanisms of action in mouse islets and rats.  Diabetologia. 2009;  52 855-862
• 22 Abbud R, Smith MS. Altered luteinizing hormone and prolactin responses to excitatory amino acids during lactation.  Neuroendocrinology. 1993;  58 454-464
• 23 Wahab F, Bano R, Jabeen S, Irfan S, Shahab M. Effect of peripheral kisspeptin administration on adiponectin, leptin, and resistin secretion under fed and fasting conditions in the adult male rhesus monkey (Macaca mulatta).  Horm Metab Res. 2010;  42 570-574
• 24 Vikman J, Ahrén B. Inhibitory effect of kisspeptins on insulin secretion from isolated mouse islets.  Diabetes Obes Metab. 2009;  11 197-201
• 25 Littledike ET, Witzel DA, Whipp SC. Insulin: Evidence for inhibition of release in spontaneous hypocalcemia.  Proc Soc Exp Biol Med. 1968;  129 135-139
• 26 Brelje TC, Sorenson RL. Nutrient and hormonal regulation of the threshold of glucose-stimulated insulin secretion in isolated rat pancreases.  Endocrinology. 1988;  123 1582-1590
• 27 Hove K, Halse K. Absence of feeding-induced variations in plasma insulin in hypoglycaemic-ketonaemic cows.  Acta Vet Scand. 1978;  19 215-228
• 28 Burch PT, Trus MD, Berner DK, Leontire A, Zawalich KC, Matschinsky FM. Adaptation of glycolytic enzymes: glucose use and insulin release in rat pancreatic islets during fasting and refeeding.  Diabetes. 1981;  30 923-928
• 29 Hertelendy F, Takahashi K, Machlin LJ, Kipnis DM. The effect of chronic adrenergic blockage on the inhibition by epinephrine of growth hormone and insulin release in sheep.  Horm Metab Res. 1970;  2 257-259
• 30 Bornet FR, Jardy-Gennetier AE, Jacquet N, Stowell J. Glycaemic response to foods: impact on satiety and long-term weight regulation.  Appetite. 2007;  49 535-553
• 31 Brown RE, Imran SA, Ur E, Wilkinson M. KiSS-1 mRNA in adipose tissue is regulated by sex hormones and food intake.  Mol Cell Endocrinol. 2008;  281 64-72
• 32 Xu J, Kirigiti MA, Grove KL, Smith MS. Regulation of Food Intake and GnRH/LH during Lactation: Role of Insulin and Leptin.  Endocrinology. 2009;  150 4231-4240
• 33 Horikoshi Y, Matsumoto H, Takatsu Y, Ohtaki T, Kitada C, Usuki S, Fujino M. Dramatic elevation of plasma metastin concentrations in human pregnancy: Metastin as a novel placenta-derived hormone in humans.  Journal of Clinical Endocrinol Metab. 2003;  88 914-919
• 34 Panidis D, Rousso D, Koliakos G, Kourtis A, Katsikis I, Farmakiotis D, Votsi E, Diamanti-Kandarakis E. Plasma metastin levels are negatively correlated with insulin resistance and free androgens in women with polycystic ovary syndrome.  Fertil Steril. 2006;  85 1778-1883
• 35 de Vries L, Shtaif B, Phillip M, Gat-Yablonski G. Kispeptin serum levels in girls with central precocious puberty.  Clin Endocrinol (Oxf). 2009;  71 524-528
• 36 Whitlock BK, Daniel JA, Wilborn RR, Maxwell HS, Steele BP, Sartin JL. Interaction of Kisspeptin and the Somatotropic Axis.  Neuroendocrinology. 2010;  92 178-188
• 37 Ten SC, Gu SY, Niu YF, An XF, Yan M, He M. Central administration of kisspeptin-10 inhibits water and sodium excretion of anesthetized male rats and the involvement of arginine vasopressin.  Endocr Res. 2010;  35 128-136
• 38 Fu LY, van den Pol AN. Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism.  J Neurosci. 2010;  30 10205-10219
• 39 Nielsen JH. Direct effect of gonadal and contraceptive steroids on insulin release from mouse pancreatic islets in organ culture.  Acta Endocrinol (Copenh). 1984;  105 245-250
• 40 Winzell MS, Nogueiras R, Dieguez C, Ahrén B. Dual action of adiponectin on insulin secretion in insulin-resistant mice.  Biochem Biophys Res Commun. 2004;  321 154-160

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