Metabolic, ionic, and secretory response to D-glucose in islets from rats with acquired or inherited non-insulin-dependent diabetes.
The metabolic, ionic, and secretory response to D-glucose was investigated in islets of adult rats either injected with streptozotocin during the neonatal period (STZ rats) or presenting with inherited diabetes (GK rats). At a high concentration of D-glucose (16.7 mM), the ATP/ADP ratio was lower in islets from STZ and GK than control rats. This coincided with an impaired response of perifused islets to a rise in D-glucose concentration in terms of stimulation of insulin release, suppression of effluent radioactivity from islets prelabeled with [2-3H]adenosine, reduction in 86Rb efflux, and induction of a phosphate flush in islets prelabeled with 32P(i). The ratio in either D-[5-3H]glucose utilization or D-[2-14C]glucose oxidation at high/low hexose concentration, as well as the paired ratio between D-[2-14C]glucose oxidation and D-[5-3H]glucose utilization in islets incubated at a high concentration of the hexose, was also lower in STZ and GK rats than in control rats. Such was not the case, however, from the oxidation of [2-14C]pyruvate. Instead, the latter 2-keto acid, when tested at a 5.0 mM concentration, improved more efficiently the overall oxidative response of the islets to a rise in D-glucose concentration in STZ and GK rats than in control animals. It is proposed, therefore, that in both STZ and GK rats, the B-cell secretory defect is primarily attributable to an anomaly in oxidative glycolysis. In islets exposed to a high concentration of D-glucose, this metabolic deficiency results in impaired ATP generation, altered closing of ATP-responsive K+ channels, and, hence, diminished insulin output.
Giroix
M H
MH
Laboratoire de Physiologie de la Nutrition, URA CNRS 307, University of Paris VII, France.
Sener
A
A
Bailbe
D
D
Leclercq-Meyer
V
V
Portha
B
B
Malaisse
W J
WJ
D000241:Adenosine / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism / Q000494:pharmacology; D019289:Pyruvic Acid; D051381:Rats; D017208:Rats, Wistar; D012414:Rubidium Radioisotopes / Q000378:metabolism; D013311:Streptozocin
D010710:Phosphates; D011773:Pyruvates; D012414:Rubidium Radioisotopes; D013311:Streptozocin; D000244:Adenosine Diphosphate; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D005947:Glucose; D000241:Adenosine