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Metformin and exercise reduce muscle FAT/CD36 and lipid accumulation and blunt the progression of high-fat diet-induced hyperglycemia.
Am J Physiol Endocrinol Metab 2007; 293(1):E172-81AJ

Abstract

Derangements in skeletal muscle fatty acid (FA) metabolism associated with insulin resistance in obesity appear to involve decreased FA oxidation and increased accumulation of lipids such as ceramides and diacylglycerol (DAG). We investigated potential lipid-related mechanisms of metformin (Met) and/or exercise for blunting the progression of hyperglycemia/hyperinsulinemia and skeletal muscle insulin resistance in female Zucker diabetic fatty rats (ZDF), a high-fat (HF) diet-induced model of diabetes. Lean and ZDF rats consumed control or HF diet (48 kcal %fat) alone or with Met (500 mg/kg), with treadmill exercise, or with both exercise and Met interventions for 8 wk. HF-fed ZDF rats developed hyperglycemia (mean: 24.4 +/- 2.1 mM), impairments in muscle insulin-stimulated glucose transport, increases in the FA transporter FAT/CD36, and increases in total ceramide and DAG content. The development of hyperglycemia was significantly attenuated with all interventions, as was skeletal muscle FAT/CD36 abundance and ceramide and DAG content. Interestingly, improvements in insulin-stimulated glucose transport and increased GLUT4 transporter expression in isolated muscle were seen only in conditions that included exercise training. Reduced FA oxidation and increased triacylglycerol synthesis in isolated muscle were observed with all ZDF rats compared with lean rats (P < 0.01) and were unaltered by therapeutic intervention. However, exercise did induce modest increases in peroxisome proliferator-activated receptor-gamma coactivator-1alpha, citrate synthase, and beta-hydroxyacyl-CoA dehydrogenase activity. Thus reduction of skeletal muscle FAT/CD36 and content of ceramide and DAG may be important mechanisms by which exercise training blunts the progression of diet-induced insulin resistance in skeletal muscle.

Authors+Show Affiliations

Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17374701

Citation

Smith, Angela C., et al. "Metformin and Exercise Reduce Muscle FAT/CD36 and Lipid Accumulation and Blunt the Progression of High-fat Diet-induced Hyperglycemia." American Journal of Physiology. Endocrinology and Metabolism, vol. 293, no. 1, 2007, pp. E172-81.
Smith AC, Mullen KL, Junkin KA, et al. Metformin and exercise reduce muscle FAT/CD36 and lipid accumulation and blunt the progression of high-fat diet-induced hyperglycemia. Am J Physiol Endocrinol Metab. 2007;293(1):E172-81.
Smith, A. C., Mullen, K. L., Junkin, K. A., Nickerson, J., Chabowski, A., Bonen, A., & Dyck, D. J. (2007). Metformin and exercise reduce muscle FAT/CD36 and lipid accumulation and blunt the progression of high-fat diet-induced hyperglycemia. American Journal of Physiology. Endocrinology and Metabolism, 293(1), pp. E172-81.
Smith AC, et al. Metformin and Exercise Reduce Muscle FAT/CD36 and Lipid Accumulation and Blunt the Progression of High-fat Diet-induced Hyperglycemia. Am J Physiol Endocrinol Metab. 2007;293(1):E172-81. PubMed PMID: 17374701.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metformin and exercise reduce muscle FAT/CD36 and lipid accumulation and blunt the progression of high-fat diet-induced hyperglycemia. AU - Smith,Angela C, AU - Mullen,Kerry L, AU - Junkin,Kathryn A, AU - Nickerson,Jennifer, AU - Chabowski,Adrian, AU - Bonen,Arend, AU - Dyck,David J, Y1 - 2007/03/20/ PY - 2007/3/22/pubmed PY - 2007/9/14/medline PY - 2007/3/22/entrez SP - E172 EP - 81 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 293 IS - 1 N2 - Derangements in skeletal muscle fatty acid (FA) metabolism associated with insulin resistance in obesity appear to involve decreased FA oxidation and increased accumulation of lipids such as ceramides and diacylglycerol (DAG). We investigated potential lipid-related mechanisms of metformin (Met) and/or exercise for blunting the progression of hyperglycemia/hyperinsulinemia and skeletal muscle insulin resistance in female Zucker diabetic fatty rats (ZDF), a high-fat (HF) diet-induced model of diabetes. Lean and ZDF rats consumed control or HF diet (48 kcal %fat) alone or with Met (500 mg/kg), with treadmill exercise, or with both exercise and Met interventions for 8 wk. HF-fed ZDF rats developed hyperglycemia (mean: 24.4 +/- 2.1 mM), impairments in muscle insulin-stimulated glucose transport, increases in the FA transporter FAT/CD36, and increases in total ceramide and DAG content. The development of hyperglycemia was significantly attenuated with all interventions, as was skeletal muscle FAT/CD36 abundance and ceramide and DAG content. Interestingly, improvements in insulin-stimulated glucose transport and increased GLUT4 transporter expression in isolated muscle were seen only in conditions that included exercise training. Reduced FA oxidation and increased triacylglycerol synthesis in isolated muscle were observed with all ZDF rats compared with lean rats (P < 0.01) and were unaltered by therapeutic intervention. However, exercise did induce modest increases in peroxisome proliferator-activated receptor-gamma coactivator-1alpha, citrate synthase, and beta-hydroxyacyl-CoA dehydrogenase activity. Thus reduction of skeletal muscle FAT/CD36 and content of ceramide and DAG may be important mechanisms by which exercise training blunts the progression of diet-induced insulin resistance in skeletal muscle. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/17374701/Metformin_and_exercise_reduce_muscle_FAT/CD36_and_lipid_accumulation_and_blunt_the_progression_of_high_fat_diet_induced_hyperglycemia_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00677.2006?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -