Journal of Regional Section of Serbian Medical Association in Zajecar

Year 2006     Volumen 31     No 4
Home ] Gore/Up ]<<< ] >>> ]
UDK: 616.379-008.64-02; 612.349.8 ISSN 0350-2899 31 (2006) 4 p. 180-185

Insulin signalling pathway in skeletal muscles

Emina Sudar, Jelena Velebit, Esma R. Isenović
Institut za nuklearne nauke "Vinča" - Laboratorija za radiobiologiju i molekularnu genetiku, Beograd



Insulin (INS), the hormone of endocrine pancreas, is one of the most important vertebrate proteins. Increased circulating levels of glucose (Glu) stimulate pancreatic β cells to secrete INS by exocytosis. Insulin receptor (IR) belongs to the group of membrane receptors with tyrosine kinase activity. Skeletal muscles (SM) account for about 85% of total Glu disposal under INS stimulated conditions where it is incorporated and stored as glycogen. Glu entry into cells is a process that requires the involvement of a carrier protein in order to facilitate the movement of Glu across the plasma membrane of a cell and they are identified as glucose transporters (GLUT). In SMs, GLUT1 and GLUT4 are the primary GLUTs expressed. In SMs, INS stimulated Glu disposal is mediated via translocation of GLUT4 from intracellular storage site to the plasma membrane and GLUT1 primary mediates basal, rather than INS mediated Glu uptake. Impairment of the mechanisms responsible for this translocation leads to INS resistance. Peripheral INS resistance is a key factor in the pathogenesis of type 2 Diabetes Mellitus (DMT2) and involves defects in Glu transport system in adipocytes and SM. SM is the principal site of Glu uptake under INS stimulated conditions and INS resistance in SM has been identified as the most important site for INS resistance in DMT2 and may result from a defect at the level of Glu transport, Glu phosphorylation or glycogen synthesis. Glu transport is one of the first steps in INS stimulated Glu uptake in SM and it is a rate limiting factor in the whole Glu metabolism.
Key words: insulin, skeletal muscles, insulin resistance, Diabetes Mellitus Type 2.

: kompletan tekst rada na srpskom jeziku
Note: full text in Serbian


  1. Petrović,V. Cvijić,G. Endokrinologija. 1. izdanje, Beograd: Zavod za udžbenike i nastavna sredstva; 1997.
  2. Pessin JE, Saltiel AR. Signaling pathways in insulin action: molecular targets of insulin resistance. The Jurnal of clinical Investigations 2000; Volume 106, Number 2: 165-169.
  3. Ryder JW, Chibalin AV, Zierath JR. Intracellular mechanisms underlying increases in glucose uptake in response to insulin or exercise in skeletal muscle. Acta Phisiol Scand 2001; 171, 249-257.
  4. Korićanac G. Osobine i sinteza insulinskih receptora pod delovanjem glukokortikoida kod pacova različite starosti. Doktorska disertacija, Biološki fakultet, Beograd, 2000.
  5. Zierath JR, Krook A, Wallberg-Henriksson H. Insulin action in skeletal muscle from patients with NIDDM. Mol.and Cellular Biochemistry 1998; 182: 153-160.
  6. Chowdhury HH, Jovsek M, Kreft M, Mars T, Zorec R , Grubic Z. Insulin induced exocytosis in single, in vitro innervated human muscle fibres: a new approach. Pflugers Arch- Eur J Physiol 2005; 450: 131-135.
  7. Jensen J, Jebens E, Brennesvik OE, Ruzzin J, Soos MA, Engebretsen EML et al. Muscle glycogen inharmoniously regulates glycogen synthase activity, glucose uptake and proximal insulin signaling. AJP-Endocrinology and Metabilism 2006; 290: 154-162.
  8. Al-Khalili L, Cartee GD, Krook A. RNA interference-mediated reduction in GLUT1 inhibits serum- induced glucose transport in primary human skeletal muscle cells. Biochem and Biophysical Research Communications 2003; 307: 127-132.
  9. Al-Khalili L, Chibalin AV, Kannisto K, Zhang BB, Permert J, Holman GD et al. Insulin action in cultured human skeletal muscle cells during differentiation: assessment of cell surface GLUT4 and GLUT1 content. Cell. Mol. Life Sci. 2003; 60: 991-998.
  10. Brennan CL, Hoening M, Ferguson DC. GLUT4 but not GLUT1 expression decreases early in the development of feline obesity. Domestic Animal Endocrinology 2004; 26: 291-301.
  11. Ruzin J, Wagman AS, Jensen J. Glucocorticoid-induced insulin resistance in skeletal muscles: defects in insulin signaling and effects of a selective glycogen synthase kinase-3 inhibitor. Diabetologia 2005; 48: 2119-2130.
  12. Peterson KF, Schuman GI. Pathogenesis of skeletal muscle insulin resistance in type 2 diabetes mellitus. The American Journal of Cardiology 2002; 90: 11-18.
  13. Courtney HC, Olefskiy JM. Endocrinology. Insulin resistance. Landes Bioscience, 2003.
This work was supported by Ministry of science and protection of the environment, Serbia; project grant No 143030
  Corresponding Address:
Emina Sudar
Institut za nuklearne nauke "Vinča"
Laboratorija za radiobiologiju i molekularnu genetiku
P.O. Box 522
11001 Beograd, Srbija
Tel/Fax: 011-244-75-85

Paper received: 12.09.2006.
Paper accepted: 12.10.2006.
Published online: 31.01.2007.
Home ] Gore/Up ]<<< ] >>> ]
Infotrend Crea(c)tive Design