Glucose counterregulation during recovery from neuroglucopenia: which mechanism is important?
Neuroglucopenia (NGP), which is a serious potential hazard for all insulin-treated diabetics, stimulates many neural and hormonal responses including increased glucagon secretion and activation of beta-adrenergic receptors of the autonomic nervous system. To determine which of these responses is important in recovery from NGP, we induced NGP in baboons by the intravenous (IV) injection of 2-deoxy-D-glucose with and without beta-adrenergic blockade (propranolol) and somatostatin. Thirty minutes after the induction of NGP the animals recovered, and the mean (+/- SEM) rise in arterial plasma glucose was 6.6 +/- 0.9 mmol/L, in glycerol 0.106 +/- 0.22 mmol/L, and in beta-hydroxybutyrate 0.091 +/- 0.22 mmol/L. Animal recovery and glucose rise were uninfluenced by the infusion of propranolol (mean 30 minute plasma glucose rise of 6.2 +/- 0.8 mmol/L) and somatostatin (6.8 +/- 0.8 mmol/L). However, the combined infusion of somatostatin and propranolol prevented animal recovery and glucose rise (1.0 +/- 0.1 mmol/L). The glycerol and beta-hydroxybutyrate rises were blocked by the propranolol infusion alone. Thus, recovery from NGP and the associated rise in plasma glucose, glycerol, and beta-hydroxybutyrate are prevented by the combination of the suppression of the glucagon and beta-adrenergic response to NGP. Furthermore, if the results of our study are extrapolated to insulin-dependent diabetic patients, most of whom have an impaired glucagon response to insulin-induced hypoglycemia/neuroglucopenia, they would be critically dependent on beta-adrenergic mechanisms for recovery from NGP.
Asplin
C M
CM
Raghu
P K
PK
Koerker
D J
DJ
Palmer
J P
JP
D020155:3-Hydroxybutyric Acid; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001928:Brain Diseases, Metabolic / Q000097:blood*; D003847:Deoxyglucose / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood*; D005990:Glycerol / Q000097:blood; D006885:Hydroxybutyrates / Q000097:blood; D007003:Hypoglycemia / Q000097:blood*; D007328:Insulin / Q000097:blood; D008297:Male; D010215:Papio; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D006885:Hydroxybutyrates; D007328:Insulin; D011943:Receptors, Adrenergic, beta; D013004:Somatostatin; D005934:Glucagon; D003847:Deoxyglucose; D011433:Propranolol; D005990:Glycerol; D020155:3-Hydroxybutyric Acid; D004837:Epinephrine