AJP - Endocrinology and Metabolism, Vol 268, Issue 2 E248-E254, Copyright © 1995 by American Physiological Society
Forearm muscle insulin resistance during hypoglycemia: role of adrenergic mechanisms and hypoglycemia per se
B. Capaldo, R. Napoli, R. Guida, P. Di Bonito, S. Antoniello, M. Auletta, F. Pardo, V. Rendina and L. Sacca
Department of Internal Medicine, School of Medicine, Federico II University, Naples, Italy.
The forearm perfusion technique was used 1) to quantify the muscle
metabolism of glucose and gluconeogenic precursors in response to
insulin-induced hypoglycemia and 2) to assess the role of catecholamines
and glucose concentration, pe se. Insulin (0.5 mU.kg-1.min-1) was infused
for 4 h in three groups of healthy volunteers. In group I (n = 6), blood
glucose (BG) was maintained at its basal level (4.5 +/- 0.1 mmol/l). In
group II (n = 7), BG was allowed to fall to approximately 3 mmol/l. Group
III (n = 6) was similar to group II except that propranolol was infused
also. In addition, at 240 min, hypoglycemia was locally corrected by
intrabrachial glucose infusion while maintaining the systemic milieu
unperturbed. In group I, forearm glucose uptake (FGU) increased from 4.7
+/- 1.3 to a mean value of 37.8 +/- 5.0 mumol.l-1.min-1, whereas in group
II it remained unchanged (8.3 +/- 2.0 mumol.l-1.min-1). In group III,
propranolol partially prevented the suppression of FGU that increased to
21.6 +/- 5.2 mumol.l-1.min-1 (P < 0.05 vs. group II). Local correction
of hypoglycemia normalized the FGU response (36.5 +/- 8.0 mumol.l-1.min-1).
Muscle release of lactate, but not of alanine, was slightly higher during
hypoglycemia (P = not significant). Forearm blood flow remained unchanged
in groups I and III, whereas it increased by approximately 40% in group II
(P < 0.05). It is concluded that, during mild hypoglycemia 1) extreme
insulin resistance develops in the skeletal muscle, mediated by
beta-adrenergic stimulation and reduced glucose mass effect and 2)
mobilization of gluconeogenic precursors is only weakly activated.
