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DOI: 10.1055/s-0028-1128146
© Georg Thieme Verlag KG Stuttgart · New York
Expression and Regulation of Insulin and the Glucose Transporter GLUT8 in the Testes of Diabetic Rats
Publication History
received 03.07.2008
accepted 10.12.2008
Publication Date:
04 February 2009 (online)

Abstract
Diabetes induces several malfunctions in male germ cells. The aim of this study was to analyze the levels and localization of the glucose transporter GLUT8 and insulin in the testes of rats induced to a diabetic status by a single dose of streptozotocin. One month after inducing diabetes, the GLUT8 immunoreactivity in diabetic rats was mainly located associated to the acrosomic system of spermatids, and at low levels in Leydig cells. Neither the immunohistochemical localization of this transporter nor its levels showed any difference when compared to control rats. Furthermore, it was observed that control rat testes expressed insulin, which was diffusely located in the cytoplasm of both Leydig cells and early elongated spermatids and concentrated in a cytoplasmic compartment in the more mature spermatids. Testicular insulin levels measured by western blot were reduced by more than half in diabetic rats, although the distribution of the hormone was unchanged. These results indicate that i) insulin is produced by testicular cells, ii) insulin is depleted by streptozotocin-induced diabetes, and iii) that insulin depletion and hyperglycemia do not regulate the expression of GLUT8 in testes. These results also suggest that testicular production of insulin could play a role in regulating spermatogenesis and/or glucose metabolism in these organs.
Key words
spermatid - acrosome - streptozotocin - testis
References
- 1
Baccetti B, La Marca A, Piomboni P, Capitani S, Bruni E, Petraglia F, De Leo V.
Insulin-dependent diabetes in men is associated with hypothalamo-pituitary derangement
and with impairment in semen quality.
Hum Reprod.
2002;
17
2673-2677
MissingFormLabel
- 2
Sanguinetti RE, Ogawa K, Kurohmaru M, Hayashi Y.
Ultrastructural changes in mouse Leydig cells after streptozotocin administration.
Exp Anim.
1995;
44
71-73
MissingFormLabel
- 3
Anderson JE, Thliveris JA.
Testicular histology in streptozotocin-induced diabetes.
Anat Rec.
1986;
214
378-382
MissingFormLabel
- 4
Orth JM, Murray FT, Bardin CW.
Ultrastructural changes in Leydig cells of streptozotocin-induced diabetic rats.
Anat Rec.
1979;
195
415-430
MissingFormLabel
- 5
Anderson JE, Thliveris JA.
Morphometry and cytochemistry of Leydig cells in experimental diabetes.
Am J Anat.
1987;
180
41-48
MissingFormLabel
- 6
Ballester J, Muñoz MC, Domínguez J, Rigau T, Guinovart JJ, Rodríguez-Gil JE.
Insulin-dependent diabetes affects testicular function by FSH- and LH-linked mechanisms.
J Androl.
2004;
25
706-719
MissingFormLabel
- 7
Kim ST, Moley KH.
Paternal effect on embryo quality in diabetic mice is related to poor sperm quality
and associated with decreased glucose transporter expression.
Reproduction.
2008;
136
313-322
MissingFormLabel
- 8
Nakayama Y, Yamamoto T, Abe SI.
IGF-I, IGF-II and insulin promote differentiation of spermatogonia to primary spermatocytes
in organ culture of newt testes.
Int J Dev Biol.
1999;
43
343-347
MissingFormLabel
- 9
Silvestroni L, Modesti A, Sartori C.
Insulin-sperm interaction: effects on plasma membrane and binding to acrosome.
Arch Androl.
1992;
28
201-211
MissingFormLabel
- 10
Joost HG, Thorens B.
The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence
characteristics, and potential function of its novel members (review).
Mol Membr Biol.
2001;
18
247-256
MissingFormLabel
- 11
Wood IS, Trayhurn P.
Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins.
Br J Nutr.
2003;
89
3-9
MissingFormLabel
- 12
Doege H, Schurmann A, Bahrenberg G, Brauers A, Joost HG.
GLUT8, a novel member of the sugar transport facilitator family with glucose transport
activity.
J Biol Chem.
2000;
275
16275-16280
MissingFormLabel
- 13
Ibberson M, Uldry M, Thorens B.
GLUTX1, a novel mammalian glucose transporter expressed in the central nervous system
and insulin-sensitive tissues.
J Biol Chem.
2000;
275
4607-4612
MissingFormLabel
- 14
Gomez O, Romero A, Terrado J, Mesonero JE.
Differential expression of glucose transporter GLUT8 during mouse spermatogenesis.
Reproduction.
2006;
131
63-70
MissingFormLabel
- 15
Schurmann A, Axer H, Scheepers A, Doege H, Joost HG.
The glucose transport facilitator GLUT8 is predominantly associated with the acrosomal
region of mature spermatozoa.
Cell Tissue Res.
2002;
307
237-242
MissingFormLabel
- 16
Kim ST, Moley KH.
The expression of GLUT8, GLUT9a, and GLUT9b in the mouse testis and sperm.
Reprod Sci.
2007;
14
445-455
MissingFormLabel
- 17
Carayannopoulos MO, Chi MM, Cui Y, Pingsterhaus JM, MacKnight RA, Mueckler M, Devaskar SU, Moley KH.
GLUT8 is a glucose transporter responsible for insulin-stimulated glucose uptake in
the blastocyst.
Proc Natl Acad Sci USA.
2000;
97
7313-7318
MissingFormLabel
- 18
Pinto AB, Carayannopoulos MO, Hoehn A, Dowd L, Moley KH.
Glucose transporter 8 expression and translocation are critical for murine blastocyst
survival.
Biol Reprod.
2002;
66
1729-1733
MissingFormLabel
- 19
Romero A, Terrado J, Brot-Laroche E, Mesonero JE.
Glucose transporter GLUT8 mRNA expression in intestinal Caco-2 cells is regulated
by growth and metabolism.
Horm Metab Res.
2007;
39
62-64
MissingFormLabel
- 20
Scheepers A, Doege H, Joost HG, Schurmann A.
Mouse GLUT8: genomic organization and regulation of expression in 3T3-L1 adipocytes
by glucose.
Biochem Biophys Res Commun.
2001;
288
969-974
MissingFormLabel
- 21
Aquila S, Gentile M, Middea E, Catalano S, Ando S.
Autocrine regulation of insulin secretion in human ejaculated spermatozoa.
Endocrinology.
2005;
146
552-557
MissingFormLabel
- 22
Mesonero JE, Tanfin Z, Hilly M, Colosetti P, Mauger JP, Harbon S.
Differential expression of inositol 1,4,5-trisphosphate receptor types 1, 2, and 3
in rat myometrium and endometrium during gestation.
Biol Reprod.
2000;
63
532-537
MissingFormLabel
- 23
Burant CF, Davidson NO.
GLUT3 glucose transporter isoform in rat testis: localization, effect of diabetes
mellitus, and comparison to human testis.
Am J Physiol.
1994;
267
R1488-R1495
MissingFormLabel
- 24
Carosa E, Radico C, Giansante N, Rossi S, D’Adamo F, Stasi SM Di, Lenzi A, Jannini EA.
Ontogenetic profile and thyroid hormone regulation of type-1 and type-8 glucose transporters
in rat Sertoli cells.
Int J Androl.
2005;
28
99-106
MissingFormLabel
- 25
Gawlik V, Schmidt S, Scheepers A, Wennemuth G, Augustin R, Aumüller G, Moser M, Al-Hasani H, Kluge R, Joost HG, Schürmann A.
Targeted disruption of Slc2a8 (GLUT8) reduces motility and mitochondrial potential
of spermatozoa.
Mol Membr Biol.
2008;
25
224-235
MissingFormLabel
- 26
Douard V, Ferraris RP.
Regulation of the fructose transporter GLUT5 in health and disease.
Am J Physiol Endocrinol Metab.
2008;
295
E227-E237
MissingFormLabel
- 27
Gorovits N, Cui L, Busik JV, Ranalletta M, Hauguel de-Mouzon S, Charron MJ.
Regulation of hepatic GLUT8 expression in normal and diabetic models.
Endocrinology.
2003;
144
1703-1711
MissingFormLabel
- 28
Alquier T, Leloup C, Lorsignol A, Penicaud L.
Translocable glucose transporters in the brain: where are we in 2006?.
Diabetes.
2006;
55
((Suppl 2))
S131-S138
MissingFormLabel
- 29
Augustin R, Riley J, Moley KH.
GLUT8 contains a [DE]XXXL[LI] sorting motif and localizes to a late endosomal/lysosomal
compartment.
Traffic.
2005;
6
1196-1212
MissingFormLabel
- 30
Widmer M, Uldry M, Thorens B.
GLUT8 subcellular localization and absence of translocation to the plasma membrane
in PC12 cells and hippocampal neurons.
Endocrinology.
2005;
146
4727-4736
MissingFormLabel
- 31
Shin BC, MacKnight RA, Devaskar SU.
Glucose transporter GLUT8 translocation in neurons is not insulin responsive.
J Neurosci Res.
2004;
75
835-844
MissingFormLabel
- 32
Piroli GG, Grillo CA, Hoskin EK, Znamensky V, Katz EB, Milner TA, MacEwen BS, Charron MJ, Reagan LP.
Peripheral glucose administration stimulates the translocation of GLUT8 glucose transporter
to the endoplasmic reticulum in the rat hippocampus.
J Comp Neurol.
2002;
452
103-114
MissingFormLabel
- 33
Piroli GG, Grillo CA, Charron MJ, MacEwen BS, Reagan LP.
Biphasic effects of stress upon GLUT8 glucose transporter expression and trafficking
in the diabetic rat hippocampus.
Brain Res.
2004;
1006
28-35
MissingFormLabel
- 34
Membrez M, Hummler E, Beermann F, Haefliger JA, Savioz R, Pedrazzini T, Thorens B.
GLUT8 is dispensable for embryonic development but influences hippocampal neurogenesis
and heart function.
Mol Cell Biol.
2006;
26
4268-4276
MissingFormLabel
- 35
Rosenzweig JL, Havrankova J, Lesniak MA, Brownstein M, Roth J.
Insulin is ubiquitous in extrapancreatic tissues of rats and humans.
Proc Natl Acad Sci USA.
1980;
77
572-576
MissingFormLabel
- 36
Frese T, Bazwinsky I, Muhlbauer E, Peschke E.
Circadian and age-dependent expression patterns of GLUT2 and glucokinase in the pancreatic
beta-cell of diabetic and nondiabetic rats.
Horm Metab Res.
2007;
39
567-574
MissingFormLabel
- 37
German MS.
Glucose sensing in pancreatic islet beta cells: the key role of glucokinase and the
glycolytic intermediates.
Proc Natl Acad Sci USA.
1993;
90
1781-1785
MissingFormLabel
- 38
Matschinsky FM.
Regulation of pancreatic beta-cell glucokinase: from basics to therapeutics.
Diabetes.
2002;
51
((Suppl 3))
S394-S404
MissingFormLabel
- 39
Nakamura N, Shibata H, O’Brien DA, Mori C, Eddy EM.
Spermatogenic cell-specific type 1 hexokinase is the predominant hexokinase in sperm.
Mol Reprod Dev.
2008;
75
632-640
MissingFormLabel
- 40
Oonk RB, Grootegoed JA.
Identification of insulin receptors on rat Sertoli cells.
Mol Cell Endocrinol.
1987;
49
51-62
MissingFormLabel
- 41
Lin T, Haskell J, Vinson N, Terracio L.
Characterization of insulin and insulin-like growth factor I receptors of purified
Leydig cells and their role in steroidogenesis in primary culture: a comparative study.
Endocrinology.
1986;
119
1641-1647
MissingFormLabel
- 42
Kokk K, Veräjänkorva E, Wu XK, Tapfer H, Põldoja E, Simovart HE, Pöllänen P.
Expression of insulin signaling transmitters and glucose transporters at the protein
level in the rat testis.
Ann N Y Acad Sci.
2007;
1095
262-273
MissingFormLabel
- 43
Kojima H, Fujimiya M, Matsumura K, Nakahara T, Hara M, Chan L.
Extrapancreatic insulin-producing cells in multiple organs in diabetes.
Proc Natl Acad Sci USA.
2004;
101
2458-2463
MissingFormLabel
- 44
Szkudelski T.
The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas.
Physiol Res.
2001;
50
537-546
MissingFormLabel
- 45
Angulo C, Rauch MC, Droppelmann A, Reyes AM, Slebe JC, Delgado-López F, Guaiquil VH, Vera JC, Concha II.
Hexose transporter expression and function in mammalian spermatozoa: cellular localization
and transport of hexoses and vitamin C.
J Cell Biochem.
1998;
71
189-203
MissingFormLabel
Correspondence
Dr. J. Terrado
Department Medicina y Cirugía Animal
Facultad Ciencias Experimentales y de la Salud
Universidad CEU Cardenal Herrera
Av Seminario s.n.
46113 Moncada (Valencia)
Spain
Phone: +34/96/136 90 00
Fax: +34/96/139 52 72
Email: jterrado@uch.ceu.es