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Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
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Opioid Receptor Activation Impairs Hypoglycemic Counterregulation in Humans

Michelle Carey1,2, Rebekah Gospin1, Akankasha Goyal1

  • 1Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, NY.

Diabetes
|September 2, 2017
PubMed

Insights

Opioid receptor activation in humans mimics hypoglycemia-associated autonomic failure (HAAF), a condition that impairs glucose counterregulation. This finding suggests new strategies for safer intensive glycemic control in type 1 diabetes mellitus (T1DM).

Area of Science:

  • Endocrinology
  • Neuroscience
  • Metabolism

Background:

  • Intensive glycemic control is crucial for type 1 diabetes mellitus (T1DM) outcomes but is limited by hypoglycemia.
  • Recurrent hypoglycemia can lead to hypoglycemia-associated autonomic failure (HAAF), impairing counterregulatory responses.
  • The role of opioid receptor activation in inducing HAAF in humans remains unclear.

Purpose of the Study:

  • To investigate whether and how opioid receptor activation induces HAAF in healthy humans.
  • To elucidate the mechanisms underlying HAAF development.
  • To explore potential pharmacologic targets for improving glycemic control safety in T1DM.

Main Methods:

  • Twelve healthy subjects participated in a two-day study protocol.
  • Day 1: Euglycemic infusions of saline or morphine (0.1 μg/kg/min).
  • Day 2: Stepped hypoglycemic clamps with evaluation of counterregulatory hormones, endogenous glucose production (EGP), and symptoms.

Main Results:

  • Morphine administration significantly reduced plasma epinephrine response by approximately 30% on Day 2.
  • Opioid receptor activation led to reduced EGP and blunted hypoglycemia-associated symptoms.
  • These effects mimic key features of HAAF.

Conclusions:

  • Pharmacologic opioid receptor activation induces clinical and biochemical features of HAAF in humans.
  • This study clarifies the role of opioid receptors in HAAF development.
  • Findings suggest novel pharmacologic strategies for safer intensive glycemic control in T1DM.

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