title: Insulin resistance is associated with diminished endoplasmic reticulum stress responses in adipose tissue of healthy and diabetic subjects.
abstract: We recently showed that insulin increased ER stress in human adipose tissue. The effect of insulin resistance on ER stress is not known. It could be decreased, unchanged, or increased, depending on whether insulin regulates ER stress via the metabolic/phosphoinositide 3-kinase (PI3K) or alternate signaling pathways. To address this question, we examined effects of lipid-induced insulin resistance on insulin stimulation of ER stress. mRNAs of several ER stress markers were determined in fat biopsies obtained before and after 8-h hyperglycemic-hyperinsulinemic clamping in 13 normal subjects and in 6 chronically insulin-resistant patients with type 2 diabetes mellitus (T2DM). In normal subjects, hyperglycemia-hyperinsulinemia increased after/before mRNA ratios of several ER stress markers (determined by ER stress pathway array and by individual RT-PCR). Lipid infusion was associated with inhibition of the PI3K insulin-signaling pathway and with a decrease of hyperinsulinemia-induced ER stress responses. In chronically insulin-resistant patients with T2DM, hyperglycemic-hyperinsulinemia did not increase ER stress response marker mRNAs. In summary, insulin resistance, either produced by lipid infusions in normal subjects or chronically present in T2DM patients, was associated with decreased hyperinsulinemia-induced ER stress responses. This suggests, but does not prove, that these two phenomena were causally related.
authors.affiliation: Section of Endocrinology, Diabetes and Metabolism, Temple University School of Medicine, Philadelphia, PA Clinical Research Center, Temple University School of Medicine, Philadelphia, PA bodengh@tuhs.temple.edu.
authors.forename: Guenther
authors.initials: G
authors.lastname: Boden
authors.affiliation: Section of Endocrinology, Diabetes and Metabolism, Temple University School of Medicine, Philadelphia, PA Clinical Research Center, Temple University School of Medicine, Philadelphia, PA.
authors.forename: Peter
authors.initials: P
authors.lastname: Cheung
authors.affiliation: Clinical Research Center, Temple University School of Medicine, Philadelphia, PA.
authors.forename: Karen
authors.initials: K
authors.lastname: Kresge
authors.affiliation: Section of Endocrinology, Diabetes and Metabolism, Temple University School of Medicine, Philadelphia, PA Clinical Research Center, Temple University School of Medicine, Philadelphia, PA.
authors.forename: Carol
authors.initials: C
authors.lastname: Homko
authors.affiliation: Department of Surgery, Temple University School of Medicine, Philadelphia, PA.
authors.forename: Ben
authors.initials: B
authors.lastname: Powers
authors.affiliation: Department of Surgery, Temple University School of Medicine, Philadelphia, PA.
authors.forename: Lucas
authors.initials: L
authors.lastname: Ferrer
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004655:Emulsions; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010743:Phospholipids; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013024:Soybean Oil; D056811:Unfolded Protein Response / Q000187:drug effects
chemical_list: D004655:Emulsions; D007328:Insulin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010743:Phospholipids; D012333:RNA, Messenger; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil
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