Abstract：
:Significant progress has been made in recent years in the characterisation of the signal pathways of beta cell dysfunction and death in the pathogenesis of type 2 diabetes. Glucolipotoxicity acts as an exogenous factor whereas oxidative stress and endoplasmic reticulum stress may result from the processes of signal recognition and stimulated secretion within the beta cell. The pharmacological stimulation of secretion may thus appear to be a double-edged sword: it counteracts hyperglycaemia, but may do so at the expense of beta cell mass. So, in the long run, insulinotropic glucose-lowering drugs might do more harm than good. However, much of this logic is derived by analogy from the long-held assumption that beta cell hypersecretion imposed by insulin resistance causes the absolute secretion deficit in the later course of type 2 diabetes. In this concept the beta cell has a secondary role and loss of beta cell mass is necessary for the manifestation of type 2 diabetes. Recent studies have shown that a secretion deficit can exist well before insulin resistance and that major genetic risk factors concern beta cell function. Also, the evidence for a beta cell toxic effect of insulinotropic drugs is currently inconclusive. Assuming that the insulin secretion deficit is of pathogenetic importance in a network with insulin resistance as an aggravating factor, an insulinotropic glucose-lowering drug may do more good than harm if it relieves the beta cell from the stress of glucose overstimulation and does so without inducing hypoglycaemia.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Rustenbeck I,Baltrusch S,Tiedge Mdoi
10.1007/s00125-010-1839-0subject
Has Abstractpub_date
2010-10-01 00:00:00pages
2105-11issue
10eissn
0012-186Xissn
1432-0428journal_volume
53pub_type
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