The degree at which different organs develop insulin resistance is often not
uniform. Skeletal muscle insulin-mediated glucose disposal (which is nor-
mally responsible for 60 percent of whole body glucose disposal) is generally
more affected, followed next by insulin suppression of hepatic glucose output.
The combination of decreased peripheral glucose utilization and increased
hepatic glucose production (driven by hepatic insulin resistance as well as
increased circulating glucagon levels in type II diabetics) together contribute
to the hyperglycemia. Insulin signaling in adipose tissue appears least affected
in type II diabetics. Hyperinsulinemia, in the face of hyperglycemia and
dyslipidemia (often associated with type II diabetes), drives lipogenesis in
adipose tissue and may therefore contribute to the obesity often associated
with this disease.
C O M P R E H E N SIO N Q U E ST IO N S
A 64-year-old man is presented to his family doctor with complaints of fre-
quent episodes of dizziness and of numbness in his legs. During a routine his-
tory and physical examination, the doctor finds that the patient leads a
sedentary lifestyle, is obese (body mass index of 32), and has hypertension
(blood pressure of 200/120 mm Hg). The patient is asked to return to the clinic
a week later in the fasting state, during which time a blood specimen is
obtained, and a glucose tolerance test is performed. Humoral analysis reveals
fasting hyperglycemia, hyperinsulinemia, dyslipidemia, and glucose intoler-
ance. The diagnosis is type II diabetes mellitus.
[22.1] Alterations in substrate metabolism within which of the following
organs can be a cause for the observed humoral analysis?
[22.2] A mutation, leading to decreased activity, in the gene encoding for which
of these proteins is most consistent with this clinical presentation?
B. Glucose transporter isoform 1
C. Glycogen phosphorylase
D. Pyruvate carboxylase
E. Protein phosphatase 1