Metabolic, ionic, and secretory response to D-glucose in islets from rats with acquired or inherited non-insulin-dependent diabetes

Biochem Med Metab Biol. 1993 Dec;50(3):301-21. doi: 10.1006/bmmb.1993.1072.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism
  • Adenosine Diphosphate / analysis
  • Adenosine Triphosphate / analysis
  • Animals
  • Diabetes Mellitus, Type 2 / metabolism*
  • Glucose / metabolism
  • Glucose / pharmacology*
  • Islets of Langerhans / metabolism*
  • Phosphates / metabolism
  • Pyruvates / metabolism
  • Pyruvates / pharmacology
  • Pyruvic Acid
  • Rats
  • Rats, Wistar
  • Rubidium Radioisotopes / metabolism
  • Streptozocin

Substances

  • Phosphates
  • Pyruvates
  • Rubidium Radioisotopes
  • Streptozocin
  • Adenosine Diphosphate
  • Pyruvic Acid
  • Adenosine Triphosphate
  • Glucose
  • Adenosine