Neonatal streptozotocin injection: a model of glucotoxicity?
Adult rats injected with streptozotocin during the neonatal period displayed in the fed state moderate hyperglycemia. However, the percentages of glycated hemoglobin in erythrocytes and glycated lactate dehydrogenase in liver and pancreatic islets, as well as the sorbitol and glycogen content of the islets, were not significantly increased. Likewise, in intact islets, the ouabain-sensitive inflow of 86Rb+, and the ratio between 3H2O production from D-[2-3H]glucose and D-[5-3H]glucose were not different in control and streptozotocin-injected rats. These findings suggest that the alteration in both the mitochondrial catabolism of D-glucose and secretory response to the hexose previously documented in the islets of the latter animals are not attributable to factors such as the excessive nonenzymatic glycation of cytosolic proteins, sorbitol or glycogen accumulation, or impaired Na+, K(+)-adenosine triphosphatase (ATPase) activity. Although a contributive role of glucotoxicity in the impaired function of beta cell in this model of non-insulin-dependent diabetes should not be ruled out, it is speculated that streptozotocin might also cause a long-term damage of key mitochondrial dehydrogenases in the pancreatic beta cells and, possibly, their precursor cells.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Giroix
M H
MH
Zähner
D
D
Marynissen
G
G
Sener
A
A
Portha
B
B
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001834:Body Water / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006706:Homeostasis; D007515:Islets of Langerhans / Q000187:drug effects*; D051381:Rats; D012016:Reference Values; D012413:Rubidium / Q000493:pharmacokinetics; D013311:Streptozocin / Q000494:pharmacology*
D013311:Streptozocin; D005947:Glucose; D012413:Rubidium