Trends Endocrinol Metab: Rethinking the Relationship between Insulin and Cancer.

In addition to being a major metabolic hormone, insulin is also a growth factor that has a silky division effect on all cells, and is more pronounced in malignant cells where insulin is over-expressed.
patients with metabolic diseases (obesity, type 2 diabetes and metabolic syndrome) characterized by high insulinemia, the incidence of several cancers increased and cancer-related mortality increased.
with the increasing incidence of metabolic diseases worldwide and the widespread use of insulin and its similars in diabetes treatment, the relationship between insulin and cancer has become a clinically related issue.
clinical studies have not yet identified the extent to which high insulinemia affects cancer occurrence and prognosis.
in order to better understand the problem, improved scientific methods are needed to consider more carefully the mechanisms associated with high insulinemia and cancer.
insulin is a growth factor to promote the development of cancer insulin in addition to having a significant metabolic effect, but also has a well-known role in promoting silk division, promoting the proliferation of normal and malignant cells.
effects of insulin depend on its interaction with cell surface receptors in the complex insulin/IGF-1 family.
at physiological concentrations, insulin interacts mainly with its own subjects, and once the subject phosphates, activates multiple intracellular signaling path path paths, stimulating metabolism and silky division effects.
paths are similar to and partially shared with the IGF-1 subject (IGF-1R).
, however, insulin-induced (IR) has a special role in mediating cancer progression, as evidenced in studies in genetically modified mouse models that inhibit IR or IGF-1R.
IRs consist of two subsypes: IRs-a, which exhibit stronger filamentation, expressed mainly in fetuses and cancer cells, and IRs-b, which mainly exhibit metabolic effects, expressed mainly in insulin target tissues (liver, muscle, and fat).
IR-A is also a high affinity affector of IGF-2.
, different cells may react differently to insulin, depending on the number and quality of the expression of the subject on the cell surface.
when insulin levels exceed normal, the isomorn IGF-1R overflows because an increase in ligation concentration overcomes its lower affinity for the receptor.
, of course, serum insulin levels do not affect cancer progression due to the structural activation of the insulin signaling pathstream of IR.
high insulinemia refers to a condition in which the concentration of biologically active insulin in the system cycle increases, binding and activating its tissue receptors.
, however, from a biological point of view, we should distinguish between two different forms of high insulinemia: endotrophic high insulinemia and extrophic high insulinemia.
endogenetic high insulinemia endogenetic high insulinemia is a sign of insulin resistance and the result of a dual mechanism: reduced insulin removal rate in the liver and high secretion of prosaic insulin.
endogenetic high insulinemia is typical of inherited and/or accessory diseases such as obesity, prediabetes, type 2 diabetes and metabolic syndrome.
in these patients, a decrease in liver insulin removal rates is thought to be the cause of early systemic high insulinemia, which is caused by excessive insulin secretion in the later stages.
this resuscative high insulinemia may overcome metabolic damage, but at the same time increase the stimulation of silky division.
This is a longer-lasting condition in which higher insulin levels in the cycle are associated with excess insulinogen, a pre-hormone that binds islet cells to insulin and binds to low affinity IR (mainly a subtype).
In addition, endogenic high insulinemia is characterized by a concentration gradient between the liver and all exomen tissues, where insulin reaches the liver directly through the door system, up to 50% of insulin is bind and degraded, while other exocycic tissues pass through and then reach the liver.
exostose high insulinemia exostose high insulinemia occurs after a suppositive injection of synthetic insulin or similar.
in these patients, all tissues, including the liver, were exposed to the same concentration of insulin, which entered the bloodstream from the injection site and was evenly distributed throughout the body.
, all outer tissue is continuously exposed to higher insulin levels without the gradients first passed by the physiological liver.
addition, extron insulin concentrations need to reach levels that reduce the liver's glucose output.
, the dose of insulin must be titred to the level of insulin needed to overcome the resistance of liver tissue to insulin.
concluded that metabolic diseases characterized by high insulinemia were associated with an increased risk of cancer and cancer-related deaths.
fact, 5.6% of cancers are caused by high insulinemias such as obesity and type 2 diabetes.
has become a major public health problem because of the worldwide prevalence of these metabolic diseases.
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