Summary
In non-insulin-dependent diabetic subjects and in various animal models of spontaneous
or experimental chronic hyperglycaemia, the secretory response of the pancreatic B-cell
to a rapid rise in extracellular D-glucose concentration is characterized by a paradoxical,
early and transient fall in insulin output and/or an altered anomeric specificity.
These two features of B-cell glucotoxicity may be accounted for by the accumulation
of glycogen in the B-cell and the interference of changes in glycogenolysis with the
hexose-induced increase in glycolytic flux. The inhibitory action of D-glucose upon
glycogenolysis displaying α-stereospecificity, the metabolic and secretory response
to α-D-glucose is expected to be more severely affected than that evoked by the β-anomer.
Such a preferential alteration of the response to α-D-glucose was indeed documented
in diabetic subjects, BB rats, duct-ligated rabbits, and adult rats either injected
with streptozotocin during the neonatal period or rendered hyperglycaemic by the repeated
administration of diazoxide. In these experimental models, the attenuation, suppression
or even reversal of the anomeric preference in insulin release appeared related to
the severity and duration of the hyperglycaemic state. A clear distinction ought to
be made between these features of B-cell glucotoxicity and other etiopathogenic factors
of B-cell dysfunction, such as the long term deleterious effect of streptozotocin
upon the activity of key mitochondrial dehydrogenases.
Key words
B-Cell Glucotoxicity - Glycogen - Anomeric Malaise - Insulin Secretion
