Forearm muscle insulin resistance during hypoglycemia: role of adrenergic mechanisms and hypoglycemia per se.
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.
Capaldo
B
B
Department of Internal Medicine, School of Medicine, Federico II University, Naples, Italy.
Napoli
R
R
Guida
R
R
Di Bonito
P
P
Antoniello
S
S
Auletta
M
M
Pardo
F
F
Rendina
V
V
Saccà
L
L
D000328:Adult; D002395:Catecholamines / Q000502:physiology*; D005260:Female; D005542:Forearm; D006728:Hormones / Q000097:blood; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000503:physiopathology*; D007333:Insulin Resistance; D008297:Male; D009132:Muscles / Q000503:physiopathology*
D002395:Catecholamines; D006728:Hormones