H. Shamoon et al., INCREASED EPINEPHRINE AND SKELETAL-MUSCLE RESPONSES TO HYPOGLYCEMIA IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS, The Journal of clinical investigation, 93(6), 1994, pp. 2562-2571
We evaluated skeletal muscle counterregulation during hypoglycemia in
nine subjects with non-insulin-dependent diabetes mellitus (NIDDM) (Hb
A(1c) 9.4 +/- 0.5%, nl < 6.2%) compared with six normal controls, matc
hed for age (51 +/- 3 and 49 +/- 5 yr, respectively) and body mass ind
ex(27.3 +/- 1.2 and 27.0 +/- 2.1 kg/ m(2)). After 60 min of euglycemia
(plasma insulin similar to 140 mu U/ ml), plasma glucose was lowered
to 62 +/- 2 mg/dl by 120 min. Hypoglycemia induced a 2.2-fold greater
increase in plasma epinephrine in NIDDM (P < 0.001), while the plasma
glucagon response was blunted (P < 0.01). Hepatic glucose output ([H-3
-3]glucose) suppressed similarly during euglycemia, but during hypogly
cemia was greater in NIDDM(P < 0.001). Conversely, glucose uptake duri
ng euglycemia was 150%; greater in controls (P < 0.01) and remained pe
rsistently higher than in NIDDM during hypoglycemia. In NIDDM, plasma
FFA concentrations were approximately fivefold greater (P < 0.001), an
d plasma lactate levels were similar to 40% higher than in controls du
ring hypoglycemia (P < 0.01); the rates of glycolysis from plasma gluc
ose were similar in the two groups despite a 49% lower rate of glucose
uptake in NIDDM (3.4 +/- 0.9 vs. 6.9 +/- 1.3 mg/kg per minute, P < 0.
001). Muscle glycogen synthase activity. fell by 42% with hypoglycemia
(P < 0.01)in NIDDM but not in controls. In addition, glycogen phosphor
ylase was activated by 56% during hypoglycemia in NIDDM only (P < 0.01
). Muscle glucose-6-phosphate concentrations rose during hypoglycemia
by a twofold greater increment in NIDDM (P < 0.01). Thus, skeletal mus
cle participates in hypoglycemia counterregulation in NIDDM, directly
by decreased removal of plasma glucose and, indirectly, by providing l
actate for hepatic gluconeogenesis. Consequently, in addition to inher
ent insulin resistance in NIDDM, the enhanced plasma epinephrine respo
nse during hypoglycemia may partially offset impaired glucagon secreti
on and counteract the effects of hyperinsulinemia on Liver, fat, and s
keletal muscle.