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DOI: 10.1055/s-2002-38248
Insulin Decreases Human Adiponectin Plasma Levels
Publikationsverlauf
Received 1 October 2002
Accepted after revision 5 December 2002
Publikationsdatum:
27. März 2003 (online)
Abstract
Insulin resistance and hyperinsulinemia are known atherosclerosis risk factors. The association between adiponectin plasma levels and obesity, insulinemia, and atherosclerosis has been shown. Thus, adiponectin may be a link between hyperinsulinemia and vascular disease. In vitro data demonstrated a reduction of adiponectin expression by insulin. However, it is still unclear whether insulin regulates adiponectinemia in vivo in humans. Five healthy male volunteers were studied. Circulating adiponectin levels were determined before and during hyperinsulinemic euglycemic clamp. Adiponectin was measured by radioimmunoassay. Hyperinsulinemia (85.0 ± 33.2 at baseline vs. 482.8 ± 64.4 pmol/l during steady state; p < 0.01) was achieved using a euglycemic hyperinsulinemic clamp, keeping blood glucose levels basically unchanged during the intervention (4.6 ± 0.14 vs. 4.37 ± 0.15 mmol/l, respectively; ns). We found a significant decrease of adiponectin plasma levels during the steady state of hyperinsulinemic euglycemic clamp (26.7 ± 3.5 µg/ml) compared to baseline levels (30.4 ± 5 µg/ml; p < 0.05). Hyperinsulinemia caused a significant decrease of adiponectin plasma levels under euglycemic conditions. Considering existing data about adiponectin dependent effects, hypoadiponectinemia might at least partly be a link between hyperinsulinemia and vascular disease in metabolic syndrome.
Key words
Adiponectin - Insulin Resistance - Atherosclerosis - Diabetes - Insulin - Cytokine - Obesity
References
- 1 Funahashi T, Nakamura T, Shimomura I, Maeda K, Kuriyama H, Takahashi M, Arita Y, Kihara S, Matsuzawa Y. Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity. Intern Med. 1999; 38 (2) 202-206
- 2 Hu E, Liang P, Spiegelman B M. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem. 1996; 271 (18) 10 697-10 703
- 3 Scherer P E, Williams S, Fogliano M, Baldini G, Lodish H F. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem. 1995; 270 (45) 26 746-26 749
- 4 Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun. 1996; 221 (2) 286-289
- 5 Nakano Y, Tobe T, Choi-Miura N H, Mazda T, Tomita M. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J Biochem (Tokyo). 1996; 120 (4) 803-812
- 6 Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation. 2000; 102 (11) 1296-1301
- 7 Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999; 100 (25) 2473-2476
- 8 Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000; 20 (6) 1595-1599
- 9 Spranger J, Kroke A, Möhlig M, Bergmann M M, Ristow M, Boeing H, Pfeiffer A. Adiponectin independently protects against type 2 diabetes mellitus. Lancet. 2003; 361 226-228
- 10 Lindsay R S, Funahashi T, Hanson R L, Matsuzawa Y, Tanaka S, Tataranni P A, Knowler W C, Krakoff J. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet. 2002; 360 (9326) 57-58
- 11 Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley R E, Tataranni P A. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001; 86 (5) 1930-1935
- 12 Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, Ishigami M, Kuriyama H, Kishida K, Nishizawa H, Hotta K, Muraguchi M, Ohmoto Y, Yamashita S, Funahashi T, Matsuzawa Y. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation. 2001; 103 (8) 1057-1063
- 13 Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, Terasaka N, Inaba T, Funahashi T, Matsuzawa Y. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002; 106 (22) 2767-2770
- 14 Matsuda M, Shimomura I, Sata M, Arita Y, Nishida M, Maeda N, Kumada M, Okamoto Y, Nagaretani H, Nishizawa H, Kishida K, Komuro R, Ouchi N, Kihara S, Nagai R, Funahashi T, Matsuzawa Y. Role of adiponectin in preventing vascular stenosis- the missing link of adipo-vascular axis. J Biol Chem. 2002; 22 22
- 15 Okamoto Y, Arita Y, Nishida M, Muraguchi M, Ouchi N, Takahashi M, Igura T, Inui Y, Kihara S, Nakamura T, Yamashita S, Miyagawa J, Funahashi T, Matsuzawa Y. An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res. 2000; 32 (2) 47-50
- 16 Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002; 17 17
- 17 Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, Eto K, Yamashita T, Kamon J, Satoh H, Yano W, Nagai R, Kimura S, Kadowaki T, Noda T. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem. 2002; 24 24
- 18 Ma K, Cabrero A, Saha P K, Kojima H, Li L, Chang B H, Paul A, Chan L. Increased Beta -oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin. J Biol Chem. 2002; 277 (38) 34 658-34 661
- 19 Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2002; 290 (3) 1084-1089
- 20 Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2002 25 (Suppl. 1): S5-S20
- 21 DeFronzo R A, Tobin J D, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979; 237 (3) E214-E223
- 22 Zoccali C, Mallamaci F, Tripepi G, Benedetto F A, Cutrupi S, Parlongo S, Malatino L S, Bonanno G, Seminara G, Rapisarda F, Fatuzzo P, Buemi M, Nicocia G, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol. 2002; 13 (1) 134-141
- 23 Vionnet N, Hani E l, Dupont S, Gallina S, Francke S, Dotte S, de Matos F, Durand E, Lepretre F, Lecoeur C, Gallina P, Zekiri L, Dina C, Froguel P. Genomewide search for type 2 diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21-q24. Am J Hum Genet. 2000; 67 (6) 1470-1480
- 24 Mori Y, Otabe S, Dina C, Yasuda K, Populaire C, Lecoeur C, Vatin V, Durand E, Hara K, Okada T, Tobe K, Boutin P, Kadowaki T, Froguel P. Genome-wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate Loci on 7p and 11p. Diabetes. 2002; 51 (4) 1247-1255
- 25 Stumvoll M, Tschritter O, Fritsche A, Staiger H, Renn W, Weisser M, Machicao F, Häring H. Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. Diabetes. 2002; 51 (1) 37-41
- 26 Menzaghi C, Ercolino T, di Paola R, Berg A H, Warram J H, Scherer P E, Trischitta V, Doria A. A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes. 2002; 51 (7) 2306-2312
- 27 Kondo H, Shimomura I, Matsukawa Y, Kumada M, Takahashi M, Matsuda M, Ouchi N, Kihara S, Kawamoto T, Sumitsuji S, Funahashi T, Matsuzawa Y. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes. 2002; 51 (7) 2325-2328
- 28 Hara K, Boutin P, Mori Y, Tobe K, Dina C, Yasuda K, Yamauchi T, Otabe S, Okada T, Eto K, Kadowaki H, Hagura R, Akanuma Y, Yazaki Y, Nagai R, Taniyama M, Matsubara K, Yoda M, Nakano Y, Kimura S, Tomita M, Ito C, Froguel P, Kadowaki T. Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes. 2002; 51 (2) 536-540
- 29 Nishizawa H, Shimomura I, Kishida K, Maeda N, Kuriyama H, Nagaretani H, Matsuda M, Kondo H, Furuyama N, Kihara S, Nakamura T, Tochino Y, Funahashi T, Matsuzawa Y. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes. 2002; 51(9) 2734-2741
- 30 Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R. Adiponectin gene expression is inhibited by beta-adrenergic stimulation via protein kinase A in 3T3-L1 adipocytes. FEBS Lett. 2001; 507(2) 142-146
- 31 Comuzzie A G, Funahashi T, Sonnenberg G, Martin L J, Jacob H J, Black A E, Maas D, Takahashi M, Kihara S, Tanaka S, Matsuzawa Y, Blangero J, Cohen D, Kissebah A. The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J Clin Endocrinol Metab. 2001; 86(9) 4321-4325
J. Spranger
Department of Endocrinology, Diabetes and Nutrition
Benjamin Franklin Medical Center · Hindenburgdamm 30 · 12200 Berlin · Germany ·
Telefon: + 49 (30) 84 45-21 14
Fax: + 49 (30) 84 45-42 04 ·
eMail: spranger@mail.dife.de or joachim.spranger@medizin.fu-berlin.de