Resistin induces insulin resistance in pancreatic islets to impair glucose-induced insulin release.
An adipokine resistin, a small cysteine-rich protein, is one of the major risk factors of insulin resistance. In the present study, transiently resistin-expressing mice using adenovirus method showed an impaired glucose tolerance due to insulin resistance. We found that resistin-expressing mice exhibited impaired insulin secretory response to glucose. In addition, in vitro treatment with resistin for 1 day induced insulin resistance in pancreatic islets and impaired glucose-stimulated insulin secretion by elevating insulin release at basal glucose (2.8 mM) and suppressing insulin release at stimulatory glucose (8.3 mM). In addition, resistin inhibited insulin-induced phosphorylation of Akt in islets as well as other insulin target organs. Furthermore, resistin induced SOCS-3 expression in beta-cells. In conclusion, resistin induces insulin resistance in islet beta-cells at least partly via induction of SOCS-3 expression and reduction of Akt phosphorylation and impairs glucose-induced insulin secretion.
Nakata
Masanori
M
Division of Integrative Physiology, Department of Physiology, Jichi Medical University, School of Medicine, Shimotsuke, Tochigi 329-0498, Japan. nakata@jichi.ac.jp
Okada
Takashi
T
Ozawa
Keiya
K
Yada
Toshihiko
T
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D005822:Genetic Vectors / Q000008:administration & dosage; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D052243:Resistin / Q000097:blood / Q000235:genetics / Q000494:pharmacology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D052243:Resistin; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose