Control of pulsatile insulin secretion in man

Area of Science:

• Endocrinology
• Physiology
• Metabolic Research

Background:

• Insulin secretion exhibits pulsatile patterns, essential for maintaining glucose homeostasis.
• The precise control mechanisms and physiological significance of these insulin oscillations are not fully understood.

Purpose of the Study:

• To investigate the characteristics of plasma insulin oscillations in humans.
• To explore the relationship between insulin pulsatility, glucose regulation, and conditions affecting the autonomic nervous system.

Main Methods:

• Continuous central venous sampling at 1-minute intervals for up to 2.5 hours.
• Analysis of plasma insulin and glucose concentrations in basal states and under various physiological/pharmacological challenges.
• Statistical analysis of oscillation frequency and amplitude, including autocorrelation.

Main Results:

• Normal subjects displayed regular insulin oscillations with a mean period of 14 minutes.
• Cholinergic, endorphin, alpha-adrenergic, or beta-adrenergic blockade did not alter oscillation frequency.
• Stimulation of insulin secretion increased oscillation amplitude, not frequency.
• Patients with vagotomy or Whipple's operation showed longer oscillation periods (33-37 min) and larger glucose swings.
• Type 2 diabetic patients exhibited significantly larger insulin-associated glucose swings compared to normal subjects.

Conclusions:

• A neural 'pacemaker' likely controls the 14-minute insulin cycle, aiding glucose homeostasis.
• Altered oscillation patterns in denervated individuals suggest a limit-cycle feedback mechanism involving insulin and glucose.
• The vagus nerve may play a hierarchical role in regulating insulin release.