Systemic and local adrenergic regulation of muscle glucose utilization during hypoglycemia in healthy subjects.
Level 2 - randomized trial
Individual randomized human physiological trial
PubMed 11872674 · doi:10.2337/diabetes.51.3.734
What was done
Twelve healthy subjects (mean age 27 ± 5 years) underwent hyperinsulinemic clamp procedures consisting of 60 minutes of euglycemia followed by 60 minutes of hypoglycemia. Participants were randomized to receive intravenous propranolol (IV PROP, 80 µg/min), intravenous phentolamine (IV PHEN, 500 µg/min), intra-arterial propranolol (IA PROP, 25 µg/min), intra-arterial phentolamine (IA PHEN, 12 µg/min per 100 ml forearm tissue), or saline (SAL). Forearm blood flow (FBF) was measured by plethysmography alongside arteriovenous glucose difference (AV-diff) and forearm glucose uptake (FGU).
What was found
FBF increased during hypoglycemia with SAL (P < 0.001) but not with IA or IV PROP. FGU (P = 0.015) and AV-diff (P = 0.099) fell during hypoglycemia with IA PROP but did not fall with IV PROP. FBF increased during hypoglycemia with both IA and IV PHEN (P < 0.005). AV-diff decreased during hypoglycemia with IA and IV PHEN (P < 0.01), but FGU remained unchanged. Blood pressure decreased (P < 0.001) and adrenergic and neuroglycopenic symptoms increased with IV PHEN (P < 0.01).
Why it matters
This study indicates that epinephrine-mediated peripheral insulin resistance during hypoglycemia is driven by systemic rather than direct local muscular beta-adrenergic actions. Furthermore, alpha-adrenergic activation restricts peripheral vasodilation to help preserve cerebral glucose delivery.
Limits
The sample size was very small (n = 12), and the study included only young, healthy adults subjected to short-term (60-minute) induced hypoglycemia, limiting direct generalizability to diabetic patients or chronic hypoglycemia.
Cited by
- supports A continuous intravenous infusion of adrenaline (epinephrine) in humans produces demonstrable insulin resistance within one to two hours.