This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stumvoll, M. Articles by Häring, H. Search for Related Content PubMed PubMed Citation Articles by Stumvoll, M. Articles by Häring, H. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB GLYCERIN

Suppression of Systemic, Intramuscular, and Subcutaneous Adipose Tissue Lipolysis by Insulin in Humans¹

Department of Endocrinology and Metabolism, Eberhard Karls Universität, Tubingen, Germany

Address all correspondence and requests for reprints to: Dr. Michael Stumvoll, Medizinische Universitätsklinik, Otfried Müller Strasse 10, D-72076 Tubingen, Germany. E-mail: michael.stumvoll{at}med.uni-tuebingen.de

In addition to sc and visceral fat deposits, muscle has been shown to contain relevant amounts of lipids whose breakdown is subject to hormonal regulation. The aim of the present study was to determine insulin dose-response characteristics of systemic, sc adipose tissue and muscle lipolysis in humans. We used a combination of isotopic (primed continuous infusion of [d₅]glycerol) and microdialysis techniques (catheters placed in the anterior tibial muscle and sc abdominal adipose tissue) during a three-step hyperinsulinemic-euglycemic clamp (insulin infusion, 0.1, 0.25, 1.0 mU/kg·min) in 13 lean, healthy volunteers. The glycerol rate of appearance was used as the index for systemic lipolysis; interstitial glycerol concentrations were used as the index for muscle and sc adipose tissue lipolysis. The insulin concentrations resulting in a half-maximal suppression (EC₅₀) of systemic lipolysis, adipose tissue, and muscle lipolysis were 51, 68, and 44 pmol/L, respectively (between one another, P < 0.001). For each compartment there were significant correlations between the EC₅₀ and the insulin sensitivity index for glucose disposal (r > 0.67; P < 0.05). However, lipolysis (as percent of baseline) was similar during the first two insulin infusion steps, but was significantly lower in adipose (22 ± 2%) than in muscle (53 ± 4%; P < 0.001) during step 3. Although we have no direct measurement of interstitial insulin concentrations, we conclude that based on the EC₅₀ values, muscle is more sensitive with respect to the net effect of circulating insulin (transendothelial transport plus intracellular action) on lipolysis than sc adipose tissue in terms of exerting its full suppression within the physiological insulin range. This could be important in muscle for switching from preferential utilization of free fatty acids to glucose in the postprandial state. Inadequate suppression of im lipolysis resulting in excessive local availability of free fatty acids may represent a novel mechanism contributing to the pathogenesis of impaired glucose disposal, i.e. insulin resistance, in muscle.

This article has been cited by other articles:

				M. O. Weickert, M. Mohlig, J. Spranger, C. Schofl, C. V. Loeffelholz, R. L. Riepl, B. Otto, and A. F. H. Pfeiffer Effects of Euglycemic Hyperinsulinemia and Lipid Infusion on Circulating Cholecystokinin J. Clin. Endocrinol. Metab., June 1, 2008; 93(6): 2328 - 2333. [Abstract] [Full Text] [PDF]

				G. Dimitriadis, P. Mitrou, V. Lambadiari, E. Boutati, E. Maratou, E. Koukkou, M. Tzanela, N. Thalassinos, and S. A. Raptis Glucose and Lipid Fluxes in the Adipose Tissue after Meal Ingestion in Hyperthyroidism J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1112 - 1118. [Abstract] [Full Text] [PDF]

				V. Qvisth, E. Hagstrom-Toft, S. Enoksson, E. Moberg, P. Arner, and J. Bolinder Human Skeletal Muscle Lipolysis Is More Responsive to Epinephrine Than to Norepinephrine Stimulation in Vivo J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 665 - 670. [Abstract] [Full Text] [PDF]

				L. Berglund Adipose tissue, skeletal muscle, and insulin resistance across ethnicities--systems biology in action Am. J. Clinical Nutrition, December 1, 2005; 82(6): 1153 - 1154. [Full Text] [PDF]

				V. Qvisth, E. Hagstrom-Toft, S. Enoksson, R. S. Sherwin, S. Sjoberg, and J. Bolinder Combined Hyperinsulinemia and Hyperglycemia, But Not Hyperinsulinemia Alone, Suppress Human Skeletal Muscle Lipolytic Activity in Vivo J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4693 - 4700. [Abstract] [Full Text] [PDF]

				M. C Gannon, F. Q Nuttall, A. Saeed, K. Jordan, and H. Hoover An increase in dietary protein improves the blood glucose response in persons with type 2 diabetes Am. J. Clinical Nutrition, October 1, 2003; 78(4): 734 - 741. [Abstract] [Full Text] [PDF]

				E. Hagstrom-Toft, V. Qvisth, I. Nennesmo, M. Ryden, H. Bolinder, S. Enoksson, J. Bolinder, and P. Arner Marked Heterogeneity of Human Skeletal Muscle Lipolysis at Rest Diabetes, December 1, 2002; 51(12): 3376 - 3383. [Abstract] [Full Text] [PDF]

				E. Moberg, S. Sjoberg, E. Hagstrom-Toft, and J. Bolinder No apparent suppression by insulin of in vivo skeletal muscle lipolysis in nonobese women Am J Physiol Endocrinol Metab, August 1, 2002; 283(2): E295 - E301. [Abstract] [Full Text] [PDF]

				M. Sjostrand, S. Gudbjornsdottir, A. Holmang, L. Strindberg, K. Ekberg, and P. Lonnroth Measurements of Interstitial Muscle Glycerol in Normal and Insulin-Resistant Subjects J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2206 - 2211. [Abstract] [Full Text] [PDF]

				M. Stumvoll, H. G. Wahl, S. Jacob, A. Rettig, F. Machicao, and H. Haring Two novel prevalent polymorphisms in the hormone-sensitive lipase gene have no effect on insulin sensitivity of lipolysis and glucose disposal J. Lipid Res., November 1, 2001; 42(11): 1782 - 1788. [Abstract] [Full Text] [PDF]