Possible role of glycogen accumulation in B-cell glucotoxicity.
Rat pancreatic islets cultured for 1 to 5 days in the presence of 20 to 80 mmol/L D-glucose accumulate glycogen in a time- and concentration-dependent manner. When the glycogen-rich islets are incubated for 6 to 10 minutes in the absence of D-glucose, the rate of glycogenolysis is grossly proportional to the glycogen content. Exogenous D-glucose (7 to 20 mmol/L) inhibits glycogenolysis. This inhibitory effect opposes the increase in glycolytic flux attributable to the utilization of exogenous glucose. Both the inhibitory effect of D-glucose on glycogenolysis and the utilization of exogenous hexose tend to be higher with alpha- than with beta-D-glucose. In light of these findings, it is proposed that the interference of D-glucose with glycogenolysis might play a role in the paradoxical changes in insulin output and its altered anomeric specificity in response to D-glucose administration, as is often encountered in non-insulin-dependent diabetic subjects and experimental models of B-cell glucotoxicity.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Marynissen
G
G
Sener
A
A
D000818:Animals; D046508:Culture Techniques; D005260:Female; D005947:Glucose / Q000009:adverse effects*; D006003:Glycogen / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects*; D051381:Rats; D013997:Time Factors
D006003:Glycogen; D005947:Glucose