Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene

Suresh T. Mathews, Gurmant P. Singh, Mollie Ranalletta, Vivian J. Cintron, Xiaoling Qiang, Anton Scott Goustin, Kai Lin Catherine Jen, Maureen J. Charron, Willi Jahnen-Dechent, George Grunberger

Research output: Contribution to journalArticle

243 Citations (Scopus)

Abstract

Fetuin inhibits insulin-induced insulin receptor (IR) autophosphorylation and tyrosine kinase activity in vitro, in intact cells, and in vivo. The fetuin gene (AHSG) is located on human chromosome 3q27, recently identified as a susceptibility locus for type 2 diabetes and the metabolic syndrome. Here, we explore insulin signaling, glucose homeostasis, and the effect of a high-fat diet on weight gain, body fat composition, and glucose disposal in mice carrying two null alleles for the gene encoding fetuin, Ahsg (B6, 129-Ahsgtm1Mbl). Fetuin knockout (KO) mice demonstrate increased basal and insulin-stimulated phosphorylation of IR and the down-stream signaling molecules mitogen-activated protein kinase (MAPK) and Akt in liver and skeletal muscle. Glucose and insulin tolerance tests in fetuin KO mice indicate significantly enhanced glucose clearance and insulin sensitivity. Fetuin KO mice subjected to euglycemic-hyperinsulinemic clamp show augmented sensitivity to insulin, evidenced by increased glucose infusion rate (P = 0.077) and significantly increased skeletal muscle glycogen content (P < 0.05). When fed a high-fat diet, fetuin KO mice are resistant to weight gain, demonstrate significantly decreased body fat, and remain insulin sensitive. These data suggest that fetuin may play a significant role in regulating postprandial glucose disposal, insulin sensitivity, weight gain, and fat accumulation and may be a novel therapeutic target in the treatment of type 2 diabetes, obesity, and other insulin-resistant conditions.

Original languageEnglish (US)
Pages (from-to)2450-2458
Number of pages9
JournalDiabetes
Volume51
Issue number8
StatePublished - 2002

Fingerprint

Fetuins
Weight Gain
Insulin Resistance
Insulin
Knockout Mice
Genes
Glucose
High Fat Diet
Type 2 Diabetes Mellitus
Adipose Tissue
Skeletal Muscle
Glucose Clamp Technique
Insulin Receptor
Human Chromosomes
Glucose Tolerance Test
Body Composition
Mitogen-Activated Protein Kinases
Glycogen
Homeostasis
Obesity

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Mathews, S. T., Singh, G. P., Ranalletta, M., Cintron, V. J., Qiang, X., Goustin, A. S., ... Grunberger, G. (2002). Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes, 51(8), 2450-2458.

Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. / Mathews, Suresh T.; Singh, Gurmant P.; Ranalletta, Mollie; Cintron, Vivian J.; Qiang, Xiaoling; Goustin, Anton Scott; Jen, Kai Lin Catherine; Charron, Maureen J.; Jahnen-Dechent, Willi; Grunberger, George.

In: Diabetes, Vol. 51, No. 8, 2002, p. 2450-2458.

Research output: Contribution to journalArticle

Mathews, ST, Singh, GP, Ranalletta, M, Cintron, VJ, Qiang, X, Goustin, AS, Jen, KLC, Charron, MJ, Jahnen-Dechent, W & Grunberger, G 2002, 'Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene', Diabetes, vol. 51, no. 8, pp. 2450-2458.
Mathews ST, Singh GP, Ranalletta M, Cintron VJ, Qiang X, Goustin AS et al. Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes. 2002;51(8):2450-2458.
Mathews, Suresh T. ; Singh, Gurmant P. ; Ranalletta, Mollie ; Cintron, Vivian J. ; Qiang, Xiaoling ; Goustin, Anton Scott ; Jen, Kai Lin Catherine ; Charron, Maureen J. ; Jahnen-Dechent, Willi ; Grunberger, George. / Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. In: Diabetes. 2002 ; Vol. 51, No. 8. pp. 2450-2458.
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