Prevention of insulin resistance and beta-cell loss by abrogating PKCε-induced serine phosphorylation of muscle IRS-1 in Psammomys obesus

Diabetes/Metabolism Research and Reviews

Volumn 24, Issue 7, 2008, Pages 577-584

  Mack, Esther ^a   Ziv, Ehud ^a   Reuveni, Hadas ^a   Kalman, Rony ^b   Niv, Masha Y ^b   Jörns, Anne ^c   Lenzen, Sigurd ^c   Shafrir, Eleazar ^a  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^b HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^c HANNOVER MEDICAL SCHOOL   (Germany)

Author keywords

Beta cell lesion prevention; Diabetes prevention; IRS 1; Peptides inhibiting PKC ; PKC ; Serine phosphorylation; Type 2 diabetes model

Indexed keywords

ANTIDIABETIC AGENT; GLUCOSE; GLUCOSE TRANSPORTER 4; INSULIN RECEPTOR SUBSTRATE 1; PEPTIDE KCE 12; PEPTIDE KCE 16; PROTEIN KINASE B; PROTEIN KINASE C EPSILON; PROTEIN KINASE C INHIBITOR; SERINE; UNCLASSIFIED DRUG; INSULIN RECEPTOR SUBSTRATE; OLIGOPEPTIDE;

AMINO ACID SEQUENCE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING SITE; CALORIC INTAKE; CELL DAMAGE; CELL LOSS; CONTROLLED STUDY; DIABETES MELLITUS; ENZYME ACTIVITY; ENZYME INHIBITION; FEMALE; GASTROCNEMIUS MUSCLE; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLYCEMIC CONTROL; HYPERINSULINEMIA; IMMUNOHISTOCHEMISTRY; INSULIN RESISTANCE; MICROPHOTOGRAPHY; NONHUMAN; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PSAMMOMYS OBESUS; WESTERN BLOTTING; ANIMAL; DRUG ANTAGONISM; DRUG EFFECT; ENZYME ACTIVE SITE; EXPERIMENTAL DIABETES MELLITUS; GERBIL; METABOLISM; PHOSPHORYLATION;

ANIMALS; CATALYTIC DOMAIN; DIABETES MELLITUS, EXPERIMENTAL; FEMALE; GERBILLINAE; INSULIN RECEPTOR SUBSTRATE PROTEINS; INSULIN RESISTANCE; INSULIN-SECRETING CELLS; OLIGOPEPTIDES; PHOSPHORYLATION; PROTEIN KINASE C-EPSILON; SERINE;

EID: 58149145488     PISSN: 15207552     EISSN: 15207560     Source Type: Journal    
DOI: 10.1002/dmrr.881     Document Type: Article

References (20)

1. Shafrir E, Gutman A. Psammomys obesus of the Jerusalem colony: a model for nutritionally induced, non-insulin dependent diabetes. J Basic Clin Physiol Pharmacol 1993; 4: 83-99.
2. Shafrir E, Ziv E, Mosthaf L. Nutritionally induced insulin resistance and receptor defect leading to β-cell failure in animal models. Ann N Y Acad Sci 1999; 892: 223-246.
3. Ikeda Y, Ziv E, Hansen LL, et al. Cellular mechanism of nutritionally induced insulin resistance in Psammomys obesus: overexpression of protein kinase C epsilon in skeletalmuscle precedes the onset of hyperinsulinemia and hyperglycemia. Diabetes 2001; 50: 584-592.
4. Neel JV. Diabetes mellitus, a thrifty genotype rendered detrimental by progress. Am J Hum Genet 1962; 14: 353-362.
5. Bar-On H, Ben-Sasson R, Ziv E, Arar N, Shafrir E. Irreversibility of nutritionally induced NIDDM in Psammomys obesus is related to B-cell apoptosis. Pancreas 1999; 18: 259-265.
6. Donath MY, Gross D, Cerasi E, Kaiser N. Hyperglycemia-induced β-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. Diabetes 1999; 48: 738-744.
7. Jörns A, Ziv E, Tiedge M, Ziv E, Shafrir E, Lenzen S. Gradual loss of pancreatic beta-cell insulin, glucokinase and GLUT4 glucose transporter immunoreactivities during the time course of nutritionally induced type-2 diabetes in Psammomys obesus (sand rat). Virchows Arch 2002; 440: 63-69.
8. Kanety H, Moshe S, Shafrir E, Lunenfeld B, Karasik A. Hyperinsulinemia induces a reversible impairment in insulin receptor function leading to diabetes in the sand rat model of non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci U S A 1994; 91: 1853-1857.
9. Niv MY, Rubin H, Cohen J, et al. Sequence based design of kinase inhibitors applicable for therapeutics and target identification. J Biol Chem 2004; 279: 1242-1255.
10. Kheifetz V, Mochly-Rosen D. Insight into intra- and intermolecular interactions of PKC: design of specific modulators of kinase function. Pharmacol Res 2007; 55: 467-476.
11. Anis Y, Leshem O, Reuveni H, et al. Anti-diabetic effect of novel modulating peptides of G-protein coupled kinase in experimental models of diabetes. Diabetologia 2004; 47: 1232-1244.
12. Kalderon B, Gutman A, Shafrir E, Adler JH. Characterization of stages in the development of obesity syndrome in sand rat (Psammomys obesus). Diabetes 1986; 35: 717-724.
13. 632 in L6 myocytes, thereby impairing the insulin signalling pathway that promotes glucose transport. Diabetologia 2007; 50: 840-849.
14. Rui LY, Aguirre Y, Kim JK, et al. Insulin/IGF-1 and TNF alpha stimulate phosphorylation of IRS-1 at inhibitory Ser (307) V'a distinct pathways. J Clin Invest 2001; 107: 181-189.
15. 2 and θ. Diabetologia 2000; 43: 443-449.
16. De Fea K, Roth RA. Protein kinase C modulation of of insulin receptor substrate-1 tyrosine phosphorylation requires serine 612. Biochemistry 1997; 36: 12939-12947.
17. Giraud J, Haas M, Feenor EP, et al. Phosphorylation of IRS-1 at serine 522 inhibits insulin signaling. Mol Endocrinol 2007; 21: 2294-2302.
18. Henning AM, Stafan N, Lehman R, et al. Leptin downregulates insulin action through phosphorylation of serine 318 in insulin receptor substrate 1. FASEB J 2006; 20: 1206-1208.
19. Leibowitz G, Yuli M, Donath MY, et al. β- cell glucotoxicity in the Psammomys obesus model of type 2 diabetes. Diabetes 2001; 50(Suppl. 1): S113-S117.
20. Schmitz-Peiffer C, Laybutt DR, Burchfield JG, et al. Inhibition of PKCepsilon improves glucose-stimulated insulin secretion and reduces insulin clearance. Cell Metab 2007; 6: 320-328.