Mitogenic action of insulin: friend, foe or 'frenemy'?

被引：77

作者：

Draznin, B. ^{[1
]}

机构：

[1] Univ Colorado Denver, Adult Diabet Program, Aurora, CO 80045 USA

来源：

DIABETOLOGIA | 2010年 / 53卷 / 02期

关键词：

Cancer; Farnesyltransferase; Hyperinsulinaemia; Insulin resistance; Mitogenic action; EPIDERMAL-GROWTH-FACTOR; MOLECULAR-MECHANISMS; BREAST-CANCER; FACTOR-I; HYPERINSULINEMIA; FARNESYLTRANSFERASE; FARNESYLATION; PRENYLATION; TISSUES; P21RAS;

D O I：

10.1007/s00125-009-1558-6

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Either endogenous or exogenous hyperinsulinaemia in the setting of insulin resistance promotes phosphorylation and activation of farnesyltransferase, a ubiquitous enzyme that farnesylates Ras proteins. Increased availability of farnesylated Ras at the plasma membrane enhances mitogenic responsiveness of cells to various growth factors, thus contributing to progression of cancer and atherosclerosis. This effect is specific to insulin, but is not related to the type of insulin used. The stimulatory effect of hyperinsulinaemia on farnesyltransferase in the presence of insulin resistance represents one potential mechanism responsible for mitogenicity and atherogenicity of insulin.

引用

页码：229 / 233

页数：5

共 24 条

[1]

Increased cancer-related mortality for patients with type 2 diabetes who use sulforrylureas or insulin [J].

Bowker, SL ;

Majumdar, SR ;

Veugelers, P ;

Johnson, JA .

DIABETES CARE, 2006, 29 (02) :254-258

[2]

The influence of glucose-lowering therapies on cancer risk in type 2 diabetes [J].

Currie, C. J. ;

Poole, C. D. ;

Gale, E. A. M. .

DIABETOLOGIA, 2009, 52 (09) :1766-1777

[3]

Effects of insulin on prenylation as a mechanism of potentially detrimental influence of hyperinsulinemia [J].

Draznin, B ;

Miles, P ;

Kruszynska, Y ;

Olefsky, J ;

Friedman, J ;

Golovchenko, I ;

Stjernholm, R ;

Wall, K ;

Reitman, M ;

Accili, D ;

Cooksey, R ;

McClain, D ;

Goalstone, M .

ENDOCRINOLOGY, 2000, 141 (04) :1310-1316

[4]

Enhanced insulin signaling via Shc in human breast cancer [J].

Finlayson, CA ;

Chappell, J ;

Leitner, JW ;

Goalstone, ML ;

Garrity, M ;

Nawaz, S ;

Ciaraldi, TP ;

Draznin, B .

METABOLISM-CLINICAL AND EXPERIMENTAL, 2003, 52 (12) :1606-1611

[5]

Insulin stimulates the phosphorylation and activity of farnesyltransferase via the Ras-mitogen-activated protein kinase pathway [J].

Goalstone, M ;

Carel, K ;

Leitner, JW ;

Draznin, B .

ENDOCRINOLOGY, 1997, 138 (12) :5119-5124

[6]

Increased amounts of farnesylated p21Ras in tissues of hyperinsulinaemic animals [J].

Goalstone, ML ;

Wall, K ;

Kurowski, T ;

Ruderman, N ;

Pan, SJ ;

Ivy, JL ;

Moller, DE ;

Draznin, B .

DIABETOLOGIA, 1999, 42 (03) :310-316

[7]

Effect of insulin on farnesyltransferase - Specificity of insulin action and potentiation of nuclear effects of insulin-like growth factor-1, epidermal growth factor, and platelet-derived growth factor [J].

Goalstone, ML ;

Leitner, JW ;

Wall, K ;

Dolgonos, L ;

Rother, KI ;

Accili, D ;

Draznin, B .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (37) :23892-23896

[8]

Effect of insulin on farnesyltransferase activity in 3T3-L1 adipocytes [J].

Goalstone, ML ;

Draznin, B .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (44) :27585-27589

[9]

Insulin: A novel factor in carcinogenesis [J].

Gupta, K ;

Krishnaswamy, G ;

Karnad, A ;

Peiris, AN .

AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 2002, 323 (03) :140-145

[10]

Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study [J].

Hemkens, L. G. ;

Grouven, U. ;

Bender, R. ;

Guenster, C. ;

Gutschmidt, S. ;

Selke, G. W. ;

Sawicki, P. T. .

DIABETOLOGIA, 2009, 52 (09) :1732-1744

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