Passage
The liver plays a central role in maintaining blood glucose homoeostasis. It contains the highest concentration of glycogen of any organ in the body and is one of few organs that can regenerate glucose from metabolic byproducts. The liver can replenish glucose in muscle and brain tissue during times of fasting, and it can help prevent lactate accumulation during intense physical activity.Von Gierke disease is a rare autosomal recessive disorder that arises from inactivating mutations in the liver enzyme glucose 6-phosphatase (G6Pase). It affects roughly 1 in 100,000 individuals, and the resulting loss of both hormonal sensitivity and enzymatic activity leads to hypoglycemia (low blood sugar). Von Gierke can also cause an increase in blood acidity concurrent with lactate build-up. Patients typically become symptomatic shortly after birth with convulsions, hyperventilation, and tremors. Left untreated, patients may develop gout, osteoporosis, and life-threatening complications such as kidney failure and liver tumors.In an effort to examine the biochemical consequences of this disorder, scientists generated a genetically engineered mouse model with liver G6Pase expression under the control of the Tet-Off system at both alleles. Under this system, addition of the small molecule tetracycline in the water source of the mouse rapidly shuts off G6Pase gene expression and therefore can recapitulate von Gierke disease. Blood glucose and pH levels were measured daily in two groups of genetically engineered mice over 20 days: group A mice received no tetracycline and group B mice were given tetracycline starting at day 10. All mice were fed identical low-sugar diets throughout the experiment.
Adapted from Froissart R, Piraud M, Boudjemline AM, et al. Glucose-6-phosphatase deficiency. Orphanet J Rare Dis. 2011;6:27.
-Treatment with which of the following could help counteract hypoglycemia in patients with von Gierke disease?

Question

Passage
The liver plays a central role in maintaining blood glucose homoeostasis.  It contains the highest concentration of glycogen of any organ in the body and is one of few organs that can regenerate glucose from metabolic byproducts.  The liver can replenish glucose in muscle and brain tissue during times of fasting, and it can help prevent lactate accumulation during intense physical activity.Von Gierke disease is a rare autosomal recessive disorder that arises from inactivating mutations in the liver enzyme glucose 6-phosphatase (G6Pase).  It affects roughly 1 in 100,000 individuals, and the resulting loss of both hormonal sensitivity and enzymatic activity leads to hypoglycemia (low blood sugar).  Von Gierke can also cause an increase in blood acidity concurrent with lactate build-up.  Patients typically become symptomatic shortly after birth with convulsions, hyperventilation, and tremors.  Left untreated, patients may develop gout, osteoporosis, and life-threatening complications such as kidney failure and liver tumors.In an effort to examine the biochemical consequences of this disorder, scientists generated a genetically engineered mouse model with liver G6Pase expression under the control of the Tet-Off system at both alleles.  Under this system, addition of the small molecule tetracycline in the water source of the mouse rapidly shuts off G6Pase gene expression and therefore can recapitulate von Gierke disease.  Blood glucose and pH levels were measured daily in two groups of genetically engineered mice over 20 days: group A mice received no tetracycline and group B mice were given tetracycline starting at day 10.  All mice were fed identical low-sugar diets throughout the experiment.
Adapted from Froissart R, Piraud M, Boudjemline AM, et al. Glucose-6-phosphatase deficiency. Orphanet J Rare Dis. 2011;6:27.
-Treatment with which of the following could help counteract hypoglycemia in patients with von Gierke disease?

Quizplus · Accepted Answer

11ecba2d_0df0_2853_a3bf_a73bbb8e1066_MD0008_00 Hypoglycemia can normally be countered with hormones that upregulate gluconeogenesis and glycogenolysis. Normally, glucagon would help counteract hypoglycemia by upregulating gluconeogenesis and glycogenolysis in the liver. However, because von Gierke disease is insensitive to hormones, it inhibits both processes regardless of glucagon levels. Blood glucose levels must therefore be controlled by diet instead. Starch is a polysaccharide composed of several linked glucose molecules. It is slowly broken down to its constituent glucose molecules in the digestive tract by the enzyme amylase. As glucose molecules are released from starch, they enter the bloodstream and help counteract hypoglycemia. (Choice A) Insulin induces the uptake of glucose from the blood into cells and upregulates glucose storage (glycogen production) rather than synthesis (glycogenolysis). It would increase the severity of hypoglycemia. (Choice B) Vitamin A is a lipid-soluble vitamin that is required for vision, immune system maintenance, and growth. It is not involved in glucose homeostasis. (Choice C) Like glucagon, the hormone epinephrine increases blood glucose levels in most individuals. However, the passage states that von Gierke disease renders patients insensitive to hormones, making epinephrine an ineffective treatment. Educational objective: Genetic mutations that inhibit gluconeogenesis and glycogenolysis can prevent effective hormonal control of blood glucose levels. Dietary supplementation with a glucose source such as starch can help maintain glucose levels in these cases.

Passage The Liver Plays a Central Role in Maintaining Blood Glucose