CASE FILES: BIOCHEMISTRY
Which of the following changes in hepatic metabolism best explains
the increased incidence of ketoacidosis observed in type I diabetes?
A. Increased glucose uptake
B. Increased protein synthesis
C. Increased lipoprotein synthesis
D. Increased P-oxidation
E. Increased glycogen breakdown
A nsw ers
D. Glucose is the primary source of energy for the central nervous
system. A sudden decrease in circulating glucose levels will therefore
impair ATP generation, in turn impeding cognitive function. If hypo-
glycemia persists, the patient will slip into a coma and eventually die.
This unfortunately common complication in type I diabetics is a con-
sequence of oversupplementation with insulin. In contrast, a sudden
decrease in circulating insulin, glucagon, fatty acids, or triglyceride
would have little immediate effect on cognitive function.
E. Unlike the liver, skeletal muscle cannot export glucose into the cir-
culation. Once glucose enters the myocyte, it is destined for use by
that cell. Thus, intramyocellular glycogen is used as a fuel source by
skeletal muscle and therefore cannot contribute to the hyperglycemia
observed in uncontrolled type I diabetes. In contrast decreased insulin-
mediated glucose utilization by skeletal muscle and adipose will con-
suppression of hepatic glucose output. Decreased insulin-mediated
suppression of lipolysis will indirectly contribute to hyperglycemia,
by providing alterative, nonglucose, fuels (fatty acids and ketone bod-
ies) for organs such as skeletal muscle and the liver.
D. Decreased circulating insulin signals a need to increase hepatic
glucose production. This is an energetically demanding process,
driven by P-oxidation of fatty acids. However, acetyl-CoA, the major
end product of P-oxidation, cannot be used for glucose production.
Instead, acetyl-CoA is shunted into the pathway of ketone body syn-
thesis (ketogenesis). In contrast, carbon from intrahepatic glycogen
will contribute less to ketone body synthesis in uncontrolled type I
diabetes mellitus. Net glucose uptake, protein synthesis, and lipopro-
tein synthesis are decreased, as opposed to increased, during uncon-
trolled type I diabetes.