Enzymic and metabolic anomalies in islets of diabetic rats: relationship to B cell mass.
A preferential impairment of the pancreatic B cell secretory response to D-glucose occurs in adult rats injected with streptozotocin during the neonatal period. Three possible explanations for such a preferential defect were investigated in the present study. First, the time course for 3-O-methyl-D-glucose uptake by islets suggested that the anomaly in hexose transport was mainly attributable to a decrease in the space accessible to the D-glucose analog commensurate with the decrease in B cell mass, rather than to a delayed equilibration of hexose concentration across the B cell plasma membrane. Second, the activity of glucose-6-phosphatase was found to be equally low in islets from diabetic and control rats, ruling out the futile cycling between D-glucose and D-glucose 6-phosphate as a cause for the preferential alteration of the secretory response to the hexose. Third, the activity of flavine adenine dinucleotide-linked glycerophosphate dehydrogenase was found to be decreased to a greater relative extent than the B cell mass. This coincided with an impaired generation of 3HOH from L-[2-3H] glycerol in intact islets. It is proposed, therefore, that an altered circulation in the glycerol phosphate shuttle may play a major role in the impaired process of glucose-stimulated insulin release in this model of noninsulin-dependent diabetes.
Giroix
M H
MH
Laboratoire de Physiopathologie de la Nutrition, CNRS URA-307, Université de Paris VII, France.
Baetens
D
D
Rasschaert
J
J
Leclercq-Meyer
V
V
Sener
A
A
Portha
B
B
Malaisse
W J
WJ
D019325:3-O-Methylglucose; D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D005934:Glucagon / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008757:Methylglucosides / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D008757:Methylglucosides; D019325:3-O-Methylglucose; D005934:Glucagon; D005993:Glycerolphosphate Dehydrogenase; D005969:Glutamate Dehydrogenase; D005952:Glucose-6-Phosphatase