The ß-cell glucose toxicity hypothesis: Attractive but difficult to prove.
Metabolism
; 124: 154870, 2021 11.
Article
in En
| MEDLINE
| ID: mdl-34480921
ABSTRACT
ß cells in the hyperglycemic environment of diabetes have marked changes in phenotype and function that are largely reversible if glucose levels can be returned to normal. A leading hypothesis is that these changes are caused by the elevated glucose levels leading to the concept of glucose toxicity. Support for the glucose toxicity hypothesis is largely circumstantial, but little progress has been made in defining the responsible mechanisms. Then questions emerge that are difficult to answer. In the very earliest stages of diabetes development, there is a dramatic loss of glucose-induced first-phase insulin release (FPIR) with only trivial elevations of blood glucose levels. A related question is how impaired insulin action on target tissues such as liver, muscle and fat can cause increased insulin secretion. The existence of a sophisticated feedback mechanism between insulin secretion and insulin action on peripheral tissues driven by glucose has been postulated, but it has been difficult to measure increases in blood glucose levels that might have been expected. These complexities force us to challenge the simplicity of the glucose toxicity hypothesis and feedback mechanisms. It may turn out that glucose is somehow driving all of these changes, but we must develop new questions and experimental approaches to test the hypothesis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Insulin Resistance
/
Diabetes Mellitus, Type 1
/
Diabetes Mellitus, Type 2
/
Insulin-Secreting Cells
/
Insulin Secretion
/
Glucose
Limits:
Humans
Language:
En
Journal:
Metabolism
Year:
2021
Document type:
Article