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J Endocrinol Invest. 2016 Dec;39(12):1365-1376. Epub 2016 Jul 1.

Insulin, insulin receptors, and cancer.

Author information

1
Endocrinology, Garibaldi-Nesima Medical Center, Via Palermo 636, 95122, Catania, Italy. vigneri@unict.it.
2
Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy. vigneri@unict.it.
3
Humanitas, Catania Cancer Center, Catania, Italy. vigneri@unict.it.
4
CNR, Institute of Bioimages and Biostructures, Catania, Italy. vigneri@unict.it.
5
University of California, San Francisco, CA, USA.
6
Endocrinology, Garibaldi-Nesima Medical Center, Via Palermo 636, 95122, Catania, Italy.
7
Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Abstract

Insulin is a major regulator of cell metabolism but, in addition, is also a growth factor. Insulin effects in target cells are mediated by the insulin receptor (IR), a transmembrane protein with enzymatic (tyrosine kinase) activity. The insulin receptor, however, is represented by a heterogeneous family of proteins, including two different IR isoforms and also hybrid receptors resulting from the IR hemireceptor combination with a hemireceptor of the cognate IGF-1 receptor. These different receptors may bind insulin and its analogs with different affinity and produce different biologic effects. Since many years, it is known that many cancer cells require insulin for optimal in vitro growth. Recent data indicate that: (1) insulin stimulates growth mainly via its own receptor and not the IGF-1 receptor; (2) in many cancer cells, the IR is overexpressed and the A isoform, which has a predominant mitogenic effect, is more represented than the B isoform. These characteristics provide a selective growth advantage to malignant cells when exposed to insulin. For this reason, all conditions of hyperinsulinemia, both endogenous (prediabetes, metabolic syndrome, obesity, type 2 diabetes before pancreas exhaustion and polycystic ovary syndrome) and exogenous (type 1 diabetes) will increase the risk of cancer. Cancer-related mortality is also increased in patients exposed to hyperinsulinemia but other factors, related to the different diseases, may also contribute. The complexity of the diseases associated with hyperinsulinemia and their therapies does not allow a precise evaluation of the cancer-promoting effect of hyperinsulinemia, but its detrimental effect on cancer incidence and mortality is well documented.

KEYWORDS:

Diabetes and cancer; Hybrid receptors; IR isoforms; Insulin; Insulin receptor

PMID:
27368923
DOI:
10.1007/s40618-016-0508-7
[Indexed for MEDLINE]

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