Endocrine regulation of G-protein subunit production in an animal model of type 2 diabetes mellitus

B. D. Rodgers, M. Bernier, M. A. Levine

    Research output: Contribution to journalArticle

    Abstract

    Adipocyte β-adrenergic sensitivity is compromised in animal models of obesity and type 2 diabetes. Although changes in the membrane concentrations of G-protein alpha subunits (Gα) have been implicated, it remains to be determined how these changes are affected by insulin resistance in the different animal models. Because previous studies used young animals, we measured the concentrations of Gα and Gβ subunits in epididymal fat from aged (48 weeks old) db/db mice and from their lean littermates to more closely reproduce the model of type 2 diabetes mellitus. Levels of immunoreactive Gαs, Gαi1/2, Gαo and Gαq/11 were all significantly greater in adipocyte membranes from the db/db mice than in membranes from their lean non-diabetic littermate controls. Levels of Gαi1 and Gαi2 were also individually determined and although they appeared to be slightly higher in db/db membranes, these differences were not significant. Although the levels of both Gαs isoforms were elevated, levels of the 42 and 46 kDa proteins rose by approximately 42% and 20% respectively, indicating differential protein processing of Gαs. By contrast, levels of Gαi3 were similar in the two groups. The levels of common Gβ and Gβ2 were also elevated in db/db mice, whereas Gβ1 and Gβ4 levels were not different. To determine whether these changes were due to insulin resistance per se or to elevated glucocorticoid production, G-protein subunit levels were quantified in whole cell lysates from 3T3-L1 adipocytes that were stimulated with different concentrations of either insulin or corticosterone. Although none of the subunit levels was affected by insulin, the levels of both Gαs isoforms were increased equally by corticosterone in a concentration-dependent manner. Since glucocorticoids are known regulators of Gαs gene expression in many cell types and in adipocytes from diabetic rodents, the results presented herein appear to more accurately reflect diabetic pathophysiology than do those of previous studies which report a decrease in Gαs levels. Taken together, these results indicate that most of the selective changes in G-protein subunit production in adipocytes from this animal model of type 2 diabetes may not be due to diminished insulin sensitivity, but may be due to other endocrine or metabolic abnormalities associated with the diabetic phenotype.

    Original languageEnglish (US)
    Pages (from-to)509-515
    Number of pages7
    JournalJournal of Endocrinology
    Volume168
    Issue number3
    DOIs
    StatePublished - 2001

    Fingerprint

    Protein Subunits
    GTP-Binding Proteins
    Adipocytes
    Type 2 Diabetes Mellitus
    Animal Models
    Insulin Resistance
    Membranes
    Corticosterone
    Glucocorticoids
    Protein Isoforms
    Insulin
    GTP-Binding Protein alpha Subunits
    3T3-L1 Cells
    Regulator Genes
    Adrenergic Agents
    Rodentia
    Proteins
    Obesity
    Fats
    Phenotype

    ASJC Scopus subject areas

    • Endocrinology

    Cite this

    Endocrine regulation of G-protein subunit production in an animal model of type 2 diabetes mellitus. / Rodgers, B. D.; Bernier, M.; Levine, M. A.

    In: Journal of Endocrinology, Vol. 168, No. 3, 2001, p. 509-515.

    Research output: Contribution to journalArticle

    Rodgers, B. D. ; Bernier, M. ; Levine, M. A. / Endocrine regulation of G-protein subunit production in an animal model of type 2 diabetes mellitus. In: Journal of Endocrinology. 2001 ; Vol. 168, No. 3. pp. 509-515.
    @article{3c2f1fa67ca244f6809914a2580a5508,
    title = "Endocrine regulation of G-protein subunit production in an animal model of type 2 diabetes mellitus",
    abstract = "Adipocyte β-adrenergic sensitivity is compromised in animal models of obesity and type 2 diabetes. Although changes in the membrane concentrations of G-protein alpha subunits (Gα) have been implicated, it remains to be determined how these changes are affected by insulin resistance in the different animal models. Because previous studies used young animals, we measured the concentrations of Gα and Gβ subunits in epididymal fat from aged (48 weeks old) db/db mice and from their lean littermates to more closely reproduce the model of type 2 diabetes mellitus. Levels of immunoreactive Gαs, Gαi1/2, Gαo and Gαq/11 were all significantly greater in adipocyte membranes from the db/db mice than in membranes from their lean non-diabetic littermate controls. Levels of Gαi1 and Gαi2 were also individually determined and although they appeared to be slightly higher in db/db membranes, these differences were not significant. Although the levels of both Gαs isoforms were elevated, levels of the 42 and 46 kDa proteins rose by approximately 42{\%} and 20{\%} respectively, indicating differential protein processing of Gαs. By contrast, levels of Gαi3 were similar in the two groups. The levels of common Gβ and Gβ2 were also elevated in db/db mice, whereas Gβ1 and Gβ4 levels were not different. To determine whether these changes were due to insulin resistance per se or to elevated glucocorticoid production, G-protein subunit levels were quantified in whole cell lysates from 3T3-L1 adipocytes that were stimulated with different concentrations of either insulin or corticosterone. Although none of the subunit levels was affected by insulin, the levels of both Gαs isoforms were increased equally by corticosterone in a concentration-dependent manner. Since glucocorticoids are known regulators of Gαs gene expression in many cell types and in adipocytes from diabetic rodents, the results presented herein appear to more accurately reflect diabetic pathophysiology than do those of previous studies which report a decrease in Gαs levels. Taken together, these results indicate that most of the selective changes in G-protein subunit production in adipocytes from this animal model of type 2 diabetes may not be due to diminished insulin sensitivity, but may be due to other endocrine or metabolic abnormalities associated with the diabetic phenotype.",
    author = "Rodgers, {B. D.} and M. Bernier and Levine, {M. A.}",
    year = "2001",
    doi = "10.1677/joe.0.1680509",
    language = "English (US)",
    volume = "168",
    pages = "509--515",
    journal = "Journal of Endocrinology",
    issn = "0022-0795",
    publisher = "Society for Endocrinology",
    number = "3",

    }

    TY - JOUR

    T1 - Endocrine regulation of G-protein subunit production in an animal model of type 2 diabetes mellitus

    AU - Rodgers, B. D.

    AU - Bernier, M.

    AU - Levine, M. A.

    PY - 2001

    Y1 - 2001

    N2 - Adipocyte β-adrenergic sensitivity is compromised in animal models of obesity and type 2 diabetes. Although changes in the membrane concentrations of G-protein alpha subunits (Gα) have been implicated, it remains to be determined how these changes are affected by insulin resistance in the different animal models. Because previous studies used young animals, we measured the concentrations of Gα and Gβ subunits in epididymal fat from aged (48 weeks old) db/db mice and from their lean littermates to more closely reproduce the model of type 2 diabetes mellitus. Levels of immunoreactive Gαs, Gαi1/2, Gαo and Gαq/11 were all significantly greater in adipocyte membranes from the db/db mice than in membranes from their lean non-diabetic littermate controls. Levels of Gαi1 and Gαi2 were also individually determined and although they appeared to be slightly higher in db/db membranes, these differences were not significant. Although the levels of both Gαs isoforms were elevated, levels of the 42 and 46 kDa proteins rose by approximately 42% and 20% respectively, indicating differential protein processing of Gαs. By contrast, levels of Gαi3 were similar in the two groups. The levels of common Gβ and Gβ2 were also elevated in db/db mice, whereas Gβ1 and Gβ4 levels were not different. To determine whether these changes were due to insulin resistance per se or to elevated glucocorticoid production, G-protein subunit levels were quantified in whole cell lysates from 3T3-L1 adipocytes that were stimulated with different concentrations of either insulin or corticosterone. Although none of the subunit levels was affected by insulin, the levels of both Gαs isoforms were increased equally by corticosterone in a concentration-dependent manner. Since glucocorticoids are known regulators of Gαs gene expression in many cell types and in adipocytes from diabetic rodents, the results presented herein appear to more accurately reflect diabetic pathophysiology than do those of previous studies which report a decrease in Gαs levels. Taken together, these results indicate that most of the selective changes in G-protein subunit production in adipocytes from this animal model of type 2 diabetes may not be due to diminished insulin sensitivity, but may be due to other endocrine or metabolic abnormalities associated with the diabetic phenotype.

    AB - Adipocyte β-adrenergic sensitivity is compromised in animal models of obesity and type 2 diabetes. Although changes in the membrane concentrations of G-protein alpha subunits (Gα) have been implicated, it remains to be determined how these changes are affected by insulin resistance in the different animal models. Because previous studies used young animals, we measured the concentrations of Gα and Gβ subunits in epididymal fat from aged (48 weeks old) db/db mice and from their lean littermates to more closely reproduce the model of type 2 diabetes mellitus. Levels of immunoreactive Gαs, Gαi1/2, Gαo and Gαq/11 were all significantly greater in adipocyte membranes from the db/db mice than in membranes from their lean non-diabetic littermate controls. Levels of Gαi1 and Gαi2 were also individually determined and although they appeared to be slightly higher in db/db membranes, these differences were not significant. Although the levels of both Gαs isoforms were elevated, levels of the 42 and 46 kDa proteins rose by approximately 42% and 20% respectively, indicating differential protein processing of Gαs. By contrast, levels of Gαi3 were similar in the two groups. The levels of common Gβ and Gβ2 were also elevated in db/db mice, whereas Gβ1 and Gβ4 levels were not different. To determine whether these changes were due to insulin resistance per se or to elevated glucocorticoid production, G-protein subunit levels were quantified in whole cell lysates from 3T3-L1 adipocytes that were stimulated with different concentrations of either insulin or corticosterone. Although none of the subunit levels was affected by insulin, the levels of both Gαs isoforms were increased equally by corticosterone in a concentration-dependent manner. Since glucocorticoids are known regulators of Gαs gene expression in many cell types and in adipocytes from diabetic rodents, the results presented herein appear to more accurately reflect diabetic pathophysiology than do those of previous studies which report a decrease in Gαs levels. Taken together, these results indicate that most of the selective changes in G-protein subunit production in adipocytes from this animal model of type 2 diabetes may not be due to diminished insulin sensitivity, but may be due to other endocrine or metabolic abnormalities associated with the diabetic phenotype.

    UR - http://www.scopus.com/inward/record.url?scp=0035086468&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0035086468&partnerID=8YFLogxK

    U2 - 10.1677/joe.0.1680509

    DO - 10.1677/joe.0.1680509

    M3 - Article

    VL - 168

    SP - 509

    EP - 515

    JO - Journal of Endocrinology

    JF - Journal of Endocrinology

    SN - 0022-0795

    IS - 3

    ER -