title: Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups.
abstract: Prolonged food deprivation in mammals typically reduces glucose, insulin, and thyroid hormone (TH) concentrations, as well as tissue deiodinase (DI) content and activity, which, collectively, suppress metabolism. However, in elephant seal pups, prolonged fasting does not suppress TH levels; it is associated with upregulation of adipose TH-mediated cellular mechanisms and adipose-specific insulin resistance. The functional relevance of this apparent paradox and the effects of glucose and insulin on TH-mediated signaling in an insulin-resistant tissue are not well defined. To address our hypothesis that insulin increases adipose TH signaling in pups during extended fasting, we assessed the changes in TH-associated genes in response to an insulin infusion in early- and late-fasted pups. In late fasting, insulin increased DI1, DI2, and THrβ-1 mRNA expression by 566%, 44%, and 267% at 60 min postinfusion, respectively, with levels decreasing by 120 min. Additionally, we performed a glucose challenge in late-fasted pups to differentiate between insulin- and glucose-mediated effects on TH signaling. In contrast to the insulin-induced effects, glucose infusion did not increase the expressions of DI1, DI2, and THrβ-1 until 120 min, suggesting that glucose delays the onset of the insulin-induced effects. The data also suggest that fasting duration increases the sensitivity of adipose TH-mediated mechanisms to insulin, some of which may be mediated by increased glucose. These responses appear to be unique among mammals and to have evolved in elephant seals to facilitate their adaptation to tolerate an extreme physiological condition.
authors.affiliation: Department of Molecular & Cellular Biology, University of California, Merced, California; bmartinez26@ucmerced.edu.
authors.forename: Bridget
authors.initials: B
authors.lastname: Martinez
authors.affiliation: Departamento de Ciencias Químico Biológicas y Agropecuarias, Universidad de Sonora, Navojoa, Sonora, México;
authors.forename: José G
authors.initials: JG
authors.lastname: Soñanez-Organis
authors.affiliation: Department of Molecular & Cellular Biology, University of California, Merced, California;
authors.forename: Jose A
authors.initials: JA
authors.lastname: Viscarra
authors.affiliation: Veterinary Medical Diagnostic Laboratory, Texas A&M University, College Station, Texas;
authors.forename: John T
authors.initials: JT
authors.lastname: Jaques
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas; and.
authors.forename: Duncan S
authors.initials: DS
authors.lastname: MacKenzie
authors.affiliation: Department of Biology, Sonoma State University, Rohnert Park, California.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Crocker
authors.affiliation: Department of Molecular & Cellular Biology, University of California, Merced, California;
authors.forename: Rudy M
authors.initials: RM
authors.lastname: Ortiz
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D005215:Fasting / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007262:Infusions, Intravenous; D007328:Insulin / Q000494:pharmacology*; D007453:Iodide Peroxidase / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D046048:Seals, Earless; D015398:Signal Transduction / Q000187:drug effects*; D013961:Thyroid Gland / Q000187:drug effects; D037042:Thyroid Hormone Receptors beta / Q000096:biosynthesis; D013963:Thyroid Hormones / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D007453:Iodide Peroxidase; D005947:Glucose
keywords: hypothalamic-pituitary-thyroid axis; metabolism; thyroid stimulating hormone