Dehydroepiandrosterone increases β-cell mass and improves the glucose-induced insulin secretion by pancreatic islets from aged rats

被引:25
作者
Medina, MC
Souza, LC
Caperuto, LC
Anhêh, GF
Amanso, AM
Teixeira, VPA
Bordin, S
Carpinelli, AR
Britto, LRG
Barbieri, RL
Borella, MI
Carvalho, CRO [1 ]
机构
[1] Univ Sao Paulo, ICB, Dept Physiol & Biophys, BR-05389970 Sao Paulo, Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Dev & Cell Biol, Sao Paulo, Brazil
[3] Coll Med Triangulo Mineiro, Dept Gen Pathol, Uberaba, MG, Brazil
基金
巴西圣保罗研究基金会;
关键词
DHEA; insulin secretion; aged rats; Akt; IRS proteins; pancreatic islet;
D O I
10.1016/j.febslet.2005.12.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The effect of dehydroepiandrosterone (DHEA) on pancreatic islet function of aged rats, an animal model with impaired glucose-induced insulin secretion, was investigated. The following parameters were examined: morphological analysis of endocrine pancreata by immunohistochemistry; protein levels of insulin receptor, IRS-1, IRS-2, PI 3-kinase, Akt-1, and Akt-2; and static insulin secretion in isolated pancreatic islets. Pancreatic islets from DHEA-treated rats showed an increased beta-cell mass accompanied by increased Akt-1 protein level but reduced IR, IRS-1, and IRS-2 protein levels and enhanced glucose-stimulated insulin secretion. The present results suggest that DHEA may be a promising drug to prevent diabetes during aging. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:285 / 290
页数:6
相关论文
共 45 条
[1]   ALTERNATIVE PATHWAY OF INSULIN SIGNALING IN MICE WITH TARGETED DISRUPTION OF THE IRS-1 GENE [J].
ARAKI, E ;
LIPES, MA ;
PATTI, ME ;
BRUNING, JC ;
HAAG, B ;
JOHNSON, RS ;
KAHN, CR .
NATURE, 1994, 372 (6502) :186-190
[2]   Restoration of insulin secretion in pancreatic islets of protein-deficient rats by reduced expression of insulin receptor substrate (IRS)-1 and IRS-2 [J].
Araujo, EP ;
Amaral, MEC ;
Filiputti, E ;
de Souza, CT ;
Laurito, TL ;
Augusto, VD ;
Saad, MJA ;
Boschero, AC ;
Velloso, LA ;
Carneiro, EM .
JOURNAL OF ENDOCRINOLOGY, 2004, 181 (01) :25-38
[3]   Insulin-stimulated insulin secretion in single pancreatic beta cells [J].
Aspinwall, CA ;
Lakey, JRT ;
Kennedy, RT .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (10) :6360-6365
[4]   A subset of 50 secretory granules in close contact with L-type Ca2+ channels accounts for first-phase insulin secretion in mouse β-cells [J].
Barg, S ;
Eliasson, L ;
Renström, E ;
Rorsman, P .
DIABETES, 2002, 51 :S74-S82
[5]   Islet β cell expression of constitutively active Akt1/PKBα induces striking hypertrophy, hyperplasia, and hyperinsulinemia [J].
Bernal-Mizrachi, E ;
Wen, W ;
Stahlhut, S ;
Welling, CM ;
Permutt, MA .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 108 (11) :1631-1638
[6]   Life and death of the pancreatic β cells [J].
Bonner-Weir, S .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2000, 11 (09) :375-378
[7]   Protein kinase Cζ activation mediates glucagon-like peptide-1-induced pancreatic β-cell proliferation [J].
Buteau, J ;
Foisy, S ;
Rhodes, CJ ;
Carpenter, L ;
Biden, TJ ;
Prentki, M .
DIABETES, 2001, 50 (10) :2237-2243
[8]   The phosphatidylinositol/AKT/atypical PKC pathway is involved in the improved insulin sensitivity by DHEA in muscle and liver of rats in vivo [J].
Campbell, CSG ;
Caperuto, LC ;
Hirata, AE ;
Araujo, EP ;
Velloso, LA ;
Saad, MJ ;
Carvalho, CRO .
LIFE SCIENCES, 2004, 76 (01) :57-70
[9]   Aging and insulin secretion [J].
Chang, AM ;
Halter, JB .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2003, 284 (01) :E7-E12
[10]   EFFECT OF GENETIC BACKGROUND ON THE THERAPEUTIC EFFECTS OF DEHYDROEPIANDROSTERONE (DHEA) IN DIABETES-OBESITY MUTANTS AND IN AGED NORMAL MICE [J].
COLEMAN, DL ;
SCHWIZER, RW ;
LEITER, EH .
DIABETES, 1984, 33 (01) :26-32