Hyperglycemia, an abnormality that results from a breakdown of normal glucose control processes is also the result of molecular mechanisms to protect the insulin receptor? A hypothesis

Abstract

Background: Deficiency in either β-cell mass or function, or both, can lead to insufficient levels of insulin, resulting in hyperglycemia and diabetes mellitus.

Aim: This review raises the hypothesis that hyperglycemia is the result of cellular protective mechanisms of the insulin receptor.

Methodology: The methodology was a comprehensive review of existing literature on the insulin receptor and its response against molecular aggressors.

Results: Here we hypothesize that hyperglycemia is the result of a cellular mechanism of insulin receptor down-regulation to preserve its function, and at the same time, the β-cell efficiency is diminished by the initial hyperinsulinemia, which is read as a negative feedback that, if it is long-lasting, becomes irreversible due to chronic apoptotic and dedifferentiation processes.

Conclusion: An increase in glucose plasma levels and its poor control triggers serious injuries caused by glucotoxicity and lipotoxicity, which affects mainly the pancreas but also leads to a systemic damage, triggering the activation of protective pathways attempting to preserve the homeostasis and prevent progression. In turn, these pathways produce an increase in glucose by decreasing the number of insulin cell receptors, thus avoiding deleterious effects on the cell.