Syntaxin 4 transgenic mice exhibit enhanced insulin-mediated glucose uptake in skeletal muscle

Beth A. Spurlin, So Young Park, Angela K. Nevins, Jason K. Kim, Debbie C. Thurmond

Research output: Contribution to journalArticle

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Abstract

Insulin-stimulated translocation of GLUT4 vesicles from an intracellular compartment to the plasma membrane in 3T3L1 adipocytes is mediated through a syntaxin 4 (Syn4)- and Mnc18c-dependent mechanism. To investigate the impact of increasing Syn4 protein abundance on glucose homeostasis in vivo, we engineered tetracycline-repressible transgenic mice to overexpress Syn4 by fivefold in skeletal muscle and pancreas and threefold in adipose tissue. Increases in Syn4 caused increases in Munc18c protein, indicating that Syn4 regulates Munc18c expression in vivo. An important finding was that female Syn4 transgenic mice exhibited an increased rate of glucose clearance during glucose tolerance tests that was repressible by the administration of tetracycline. Insulin-stimulated glucose uptake in skeletal muscle was increased by twofold in Syn4 transgenic mice compared with wild-type mice as assessed by hyperinsulinemic-euglycemic clamp analysis, consistent with a twofold increase in insulin-stimulated GLUT4 translocation in skeletal muscle. Hepatic insulin action was unaffected. Moreover, insulin content and glucose-stimulated insulin secretion by islets isolated from Syn4 transgenic mice did not differ from that of wild-type mice. In sum, these data suggest that increasing the number of Syn4-Muncl8c "fusion sites" at the plasma membrane of skeletal muscle increases the amount of GLUT4 available to increase the overall rate of insulin-mediated glucose uptake in vivo.

Original languageEnglish
Pages (from-to)2223-2231
Number of pages9
JournalDiabetes
Volume53
Issue number9
DOIs
StatePublished - Sep 2004

Fingerprint

Qa-SNARE Proteins
Transgenic Mice
Skeletal Muscle
Insulin
Glucose
Tetracycline
Munc18 Proteins
Cell Membrane
Glucose Clamp Technique
Glucose Tolerance Test
Adipocytes
Adipose Tissue
Pancreas
Homeostasis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Spurlin, B. A., Park, S. Y., Nevins, A. K., Kim, J. K., & Thurmond, D. C. (2004). Syntaxin 4 transgenic mice exhibit enhanced insulin-mediated glucose uptake in skeletal muscle. Diabetes, 53(9), 2223-2231. https://doi.org/10.2337/diabetes.53.9.2223

Syntaxin 4 transgenic mice exhibit enhanced insulin-mediated glucose uptake in skeletal muscle. / Spurlin, Beth A.; Park, So Young; Nevins, Angela K.; Kim, Jason K.; Thurmond, Debbie C.

In: Diabetes, Vol. 53, No. 9, 09.2004, p. 2223-2231.

Research output: Contribution to journalArticle

Spurlin, BA, Park, SY, Nevins, AK, Kim, JK & Thurmond, DC 2004, 'Syntaxin 4 transgenic mice exhibit enhanced insulin-mediated glucose uptake in skeletal muscle', Diabetes, vol. 53, no. 9, pp. 2223-2231. https://doi.org/10.2337/diabetes.53.9.2223
Spurlin, Beth A. ; Park, So Young ; Nevins, Angela K. ; Kim, Jason K. ; Thurmond, Debbie C. / Syntaxin 4 transgenic mice exhibit enhanced insulin-mediated glucose uptake in skeletal muscle. In: Diabetes. 2004 ; Vol. 53, No. 9. pp. 2223-2231.
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