Summary
In order to delineate the sequence of development of the metabolic changes in the
obese-hyperglycaemic syndrome in the NZO mouse, the uptake of 2-deoxyglucose, glucose
utilization and glycogen synthesis by isolated soleus muscle in the absence and presence
of graded doses of insulin was measured, and related to the gain in body weight and
development of hyperinsulinaemia and hyperglycaemia. It was found that the NZO mice
were hyperglycaemic and hyperinsulinaemic compared to an unrelated control strain
(Balb c) from the earliest age studied (4 weeks). At 4-6 weeks, 2-deoxyglucose uptake
and glucose utilization in the absence of insulin were decreased but the sensitivity
and responsiveness to added insulin were comparable to those in the control strain.
By 11 weeks, the responsiveness to added insulin was markedly impaired, an abnormality
also seen at 52 weeks. Abnormal binding of insulin to its receptors was insufficient
explanation for the observed changes. It is concluded that hyperinsulinaemia and hyperglycaemia
develop early in NZO mice. Basal glucose transport and glucose utilization by isolated
soleus muscle are also decreased from an early age, but decreased responsiveness to
insulin in the soleus muscle is secondary and relatively late manifestations of the
syndrome.
Key-Words
NZO Mice
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Soleus Muscle
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Insulin Resistance
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Glucose Transport
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Glucose Utilization
