Glucose metabolism and pulsatile insulin release from isolated islets

Area of Science:

• Endocrinology
• Metabolic research
• Cell physiology

Background:

• Pancreatic islet function is crucial for glucose homeostasis.
• Insulin secretion is regulated by glucose and intracellular calcium dynamics.
• Metabolic pathways significantly influence insulin release.

Purpose of the Study:

• To investigate the impact of metabolic inhibition on insulin secretion and cytoplasmic calcium ([Ca(2+)](i)) in pancreatic islets.
• To elucidate the relationship between metabolic state, calcium oscillations, and pulsatile insulin release.

Main Methods:

• Individual perifusion of pancreatic islets from ob/ob mice.
• Measurement of insulin secretion and cytoplasmic Ca(2+) concentration ([Ca(2+)](i)).
• Inhibition of glycolysis (iodoacetamide) and mitochondrial metabolism (dinitrophenol, antimycin A).

Main Results:

• High glucose induced large amplitude [Ca(2+)](i) oscillations and increased insulin secretion.
• Metabolic inhibitors reduced glucose-stimulated insulin secretion to basal levels, maintaining pulsatility.
• [Ca(2+)](i) responses to inhibitors showed initial peaks and sustained elevations without oscillations.

Conclusions:

• Pulsatile insulin secretion is regulated by factors independent of [Ca(2+)](i) under basal and metabolically inhibited conditions.
• Metabolic oscillations can drive pulsatile secretion when [Ca(2+)](i) is stable.
• The specific metabolic origin (glycolytic or mitochondrial) of insulin pulses remains undetermined.