Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Apr 11;92(8):3096–3099. doi: 10.1073/pnas.92.8.3096

High fat diet-induced hyperglycemia: prevention by low level expression of a glucose transporter (GLUT4) minigene in transgenic mice.

S Ikemoto 1, K S Thompson 1, M Takahashi 1, H Itakura 1, M D Lane 1, O Ezaki 1
PMCID: PMC42111  PMID: 7724522

Abstract

High-fat intake leading to obesity contributes to the development of non-insulin-dependent diabetes mellitus (NIDDM, type 2). Similarly, mice fed a high-fat (safflower oil) diet develop defective glycemic control, hyperglycemia, and obesity. To assess the effect of a modest increase in the expression of GLUT4 (the insulin-responsive glucose transporter) on impaired glycemic control caused by fat feeding, transgenic mice harboring a GLUT4 minigene were fed a high-fat diet. Low-level tissue-specific (heart, skeletal muscle, and adipose tissue) expression of the GLUT4 minigene in transgenic mice prevented the impairment of glycemic control and accompanying hyperglycemia, but not obesity, caused by fat feeding. Thus, a small increase (< or = 2-fold) in the tissue level of GLUT4 prevents a primary symptom of the diabetic state in a mouse model, suggesting a possible target for intervention in the treatment of NIDDM.

Full text

PDF
3096

Images in this article

3098Fig. 3
on p.3098
3098Fig. 4
on p.3098

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berger J., Biswas C., Vicario P. P., Strout H. V., Saperstein R., Pilch P. F. Decreased expression of the insulin-responsive glucose transporter in diabetes and fasting. Nature. 1989 Jul 6;340(6228):70–72. doi: 10.1038/340070a0. [DOI] [PubMed] [Google Scholar]
  2. Charron M. J., Kahn B. B. Divergent molecular mechanisms for insulin-resistant glucose transport in muscle and adipose cells in vivo. J Biol Chem. 1990 May 15;265(14):7994–8000. [PubMed] [Google Scholar]
  3. Cushman S. W., Wardzala L. J. Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane. J Biol Chem. 1980 May 25;255(10):4758–4762. [PubMed] [Google Scholar]
  4. DeFronzo R. A. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988 Jun;37(6):667–687. doi: 10.2337/diab.37.6.667. [DOI] [PubMed] [Google Scholar]
  5. Ezaki O., Flores-Riveros J. R., Kaestner K. H., Gearhart J., Lane M. D. Regulated expression of an insulin-responsive glucose transporter (GLUT4) minigene in 3T3-L1 adipocytes and transgenic mice. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3348–3352. doi: 10.1073/pnas.90.8.3348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ezaki O., Higuchi M., Nakatsuka H., Kawanaka K., Itakura H. Exercise training increases glucose transporter content in skeletal muscles more efficiently from aged obese rats than young lean rats. Diabetes. 1992 Aug;41(8):920–926. doi: 10.2337/diab.41.8.920. [DOI] [PubMed] [Google Scholar]
  7. Flores-Riveros J. R., McLenithan J. C., Ezaki O., Lane M. D. Insulin down-regulates expression of the insulin-responsive glucose transporter (GLUT4) gene: effects on transcription and mRNA turnover. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):512–516. doi: 10.1073/pnas.90.2.512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Garvey W. T. Glucose transport and NIDDM. Diabetes Care. 1992 Mar;15(3):396–417. doi: 10.2337/diacare.15.3.396. [DOI] [PubMed] [Google Scholar]
  9. Garvey W. T., Huecksteadt T. P., Birnbaum M. J. Pretranslational suppression of an insulin-responsive glucose transporter in rats with diabetes mellitus. Science. 1989 Jul 7;245(4913):60–63. doi: 10.1126/science.2662408. [DOI] [PubMed] [Google Scholar]
  10. Garvey W. T., Maianu L., Huecksteadt T. P., Birnbaum M. J., Molina J. M., Ciaraldi T. P. Pretranslational suppression of a glucose transporter protein causes insulin resistance in adipocytes from patients with non-insulin-dependent diabetes mellitus and obesity. J Clin Invest. 1991 Mar;87(3):1072–1081. doi: 10.1172/JCI115068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ginsberg H., Olefsky J. M., Kimmerling G., Crapo P., Reaven G. M. Induction of hypertriglyceridemia by a low-fat diet. J Clin Endocrinol Metab. 1976 Apr;42(4):729–735. doi: 10.1210/jcem-42-4-729. [DOI] [PubMed] [Google Scholar]
  12. Hedeskov C. J., Capito K., Islin H., Hansen S. E., Thams P. Long-term fat-feeding-induced insulin resistance in normal NMRI mice: postreceptor changes of liver, muscle and adipose tissue metabolism resembling those of type 2 diabetes. Acta Diabetol. 1992;29(1):14–19. doi: 10.1007/BF00572823. [DOI] [PubMed] [Google Scholar]
  13. Ikemoto S., Thompson K. S., Itakura H., Lane M. D., Ezaki O. Expression of an insulin-responsive glucose transporter (GLUT4) minigene in transgenic mice: effect of exercise and role in glucose homeostasis. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):865–869. doi: 10.1073/pnas.92.3.865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kaestner K. H., Flores-Riveros J. R., McLenithan J. C., Janicot M., Lane M. D. Transcriptional repression of the mouse insulin-responsive glucose transporter (GLUT4) gene by cAMP. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1933–1937. doi: 10.1073/pnas.88.5.1933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kahn B. B. Facilitative glucose transporters: regulatory mechanisms and dysregulation in diabetes. J Clin Invest. 1992 May;89(5):1367–1374. doi: 10.1172/JCI115724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Koranyi L. I., Bourey R. E., Vuorinen-Markkola H., Koivisto V. A., Mueckler M., Permutt M. A., Yki-Järvinen H. Level of skeletal muscle glucose transporter protein correlates with insulin-stimulated whole body glucose disposal in man. Diabetologia. 1991 Oct;34(10):763–765. doi: 10.1007/BF00401526. [DOI] [PubMed] [Google Scholar]
  17. Leturque A., Postic C., Ferre P., Girard J. Nutritional regulation of glucose transporter in muscle and adipose tissue of weaned rats. Am J Physiol. 1991 Apr;260(4 Pt 1):E588–E593. doi: 10.1152/ajpendo.1991.260.4.E588. [DOI] [PubMed] [Google Scholar]
  18. Olefsky J., Reaven G. M., Farquhar J. W. Effects of weight reduction on obesity. Studies of lipid and carbohydrate metabolism in normal and hyperlipoproteinemic subjects. J Clin Invest. 1974 Jan;53(1):64–76. doi: 10.1172/JCI107560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reaven G. M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988 Dec;37(12):1595–1607. doi: 10.2337/diab.37.12.1595. [DOI] [PubMed] [Google Scholar]
  20. Rosenthal M., Haskell W. L., Solomon R., Widstrom A., Reaven G. M. Demonstration of a relationship between level of physical training and insulin-stimulated glucose utilization in normal humans. Diabetes. 1983 May;32(5):408–411. doi: 10.2337/diab.32.5.408. [DOI] [PubMed] [Google Scholar]
  21. Shepherd P. R., Gnudi L., Tozzo E., Yang H., Leach F., Kahn B. B. Adipose cell hyperplasia and enhanced glucose disposal in transgenic mice overexpressing GLUT4 selectively in adipose tissue. J Biol Chem. 1993 Oct 25;268(30):22243–22246. [PubMed] [Google Scholar]
  22. Sivitz W. I., DeSautel S. L., Kayano T., Bell G. I., Pessin J. E. Regulation of glucose transporter messenger RNA in insulin-deficient states. Nature. 1989 Jul 6;340(6228):72–74. doi: 10.1038/340072a0. [DOI] [PubMed] [Google Scholar]
  23. Surwit R. S., Kuhn C. M., Cochrane C., McCubbin J. A., Feinglos M. N. Diet-induced type II diabetes in C57BL/6J mice. Diabetes. 1988 Sep;37(9):1163–1167. doi: 10.2337/diab.37.9.1163. [DOI] [PubMed] [Google Scholar]
  24. Suzuki K., Kono T. Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site. Proc Natl Acad Sci U S A. 1980 May;77(5):2542–2545. doi: 10.1073/pnas.77.5.2542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wake S. A., Sowden J. A., Storlien L. H., James D. E., Clark P. W., Shine J., Chisholm D. J., Kraegen E. W. Effects of exercise training and dietary manipulation on insulin-regulatable glucose-transporter mRNA in rat muscle. Diabetes. 1991 Feb;40(2):275–279. doi: 10.2337/diab.40.2.275. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES