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J. Biol. Chem., Vol. 262, Issue 16, 7665-7671, 06, 1987
H Wallberg-Henriksson, N Zetan and J Henriksson
The mechanisms by which insulin deficiency affects muscle glucose transport
were investigated. Epitrochlearis muscles from rats with
streptozotocin-induced diabetes and from controls were incubated in vitro
for 0.5-14 h. The incubation was shown not to impair muscle energy stores
or tissue oxygenation. Diabetes decreased basal 3-O- methylglucose
transport by 40% (p less than 0.01), and insulin- stimulated (20
milli-units/ml) glucose transport capacity by 70% (p less than 0.001). In
vitro incubation gradually normalized insulin responsiveness (3.77 +/- 0.38
before versus 8.97 +/- 0.65 mumol X ml-1 X h-1 after 12 h of incubation).
Basal glucose transport remained significantly reduced. The reversal of the
insulin responsiveness did not require the presence of rat serum and,
furthermore, took place even in the absence of insulin. In fact, insulin
responsiveness was higher after incubation (14 h) with no insulin than with
100 microunits/ml insulin (9.85 +/- 0.59 versus 8.06 +/- 0.59 mumol X ml-1
X h-1, p less than 0.05). Glucose at 30 mM did not affect the normalization
of the insulin-stimulated glucose transport capacity, whereas incubation in
serum from diabetic rats resulted in a slightly (26%) blunted reversal
(7.60 +/- 0.39 versus 8.89 +/- 0.45 mumol X ml-1 X h-1 with diabetic versus
control serum for 14 h, p less than 0.05; before incubation the value was
3.87 +/- 0.40). Inhibition of protein synthesis by cycloheximide blocked
the normalization by 80%. These results suggest the presence in diabetic
serum of some labile factor that might inhibit the glucose transport
system. The results indicate that the decreased insulin-stimulated glucose
transport capacity, in the insulin-deficient diabetic muscle, is not a
direct consequence of the lack of insulin or of high glucose
concentrations.
Reversibility of decreased insulin-stimulated glucose transport capacity in diabetic muscle with in vitro incubation. Insulin is not required
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