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An intern is scrubbing into a complicated surgery that is anticipated to last for 15 hours. In preparation, the intern has not eaten from the past 15 hours. After 30 hours of fasting which of the following is most important for maintenance of normal blood glucose?

A. Glycogenolysis

B. Gluconeogenesis

C. Triacylglycerol synthesis

D. Increase Insulin release

E. Decrease muscle protein break down.


The correct answer is- B- Gluconeogenesis.

Significance of glucose

Glucose is a universal fuel molecule required for all cell types especially brain cells and the cells lacking mitochondria.

The blood glucose concentration is maintained in a range of 60-100 mg/dl to provide a constant supply of glucose to all cells especially brain cells and the cells lacking mitochondria, the latter are totally dependent upon glucose for their energy needs. Brain cells can utilize ketone bodies alternatively under conditions of prolonged fasting/starvation but glucose remains the preferred source of energy.

Fuel molecules during starvation

During starvation the energy needs are fulfilled by three types of fuels, glucose, fatty acids and ketone bodies.

Fatty acids due to long hydrophobic chains can’t cross through the Blood brain barrier (BBB), thus cannot be utilized by the brain. Ketone bodies although being relatively polar can cross through the blood brain barrier, yet they are utilized only under conditions of glucose deprivation. After several weeks of starvation, ketone bodies become the major fuel of the brain.

The oxidation of fatty acids and ketone bodies takes place in the mitochondria; hence the cells lacking mitochondria are left with no alternative fuels options except glucose to utilize. Thus an optimum glucose concentration has to be maintained for the proper functioning of these cells.

The sources of glucose include

1)      Diet

2)      Glycogen degradation, and

3)      Gluconeogenesis

Under conditions of inadequate dietary supply, the blood glucose levels are maintained initially by glucose supply from the stores (degradation of glycogen), the glycogen stores get exhausted within 14-16 hours. Thereafter the glucose is synthesized from the non-carbohydrate precursors (gluconeogenesis) such as lactate (the waste from the muscle), glycerol (the waste from the adipose tissue), and carbon skeleton of glucogenic amino acids (mainly obtained from the breakdown of muscle protein). The intermediates of TCA cycle and propionyl co A also serve as substrates for gluconeogenesis. The constant supply of substrates of gluconeogenesis, sustain the life of an individual.

In the given situation, after 30 hours of fasting, the only source of glucose is gluconeogenesis. Glycogenolysis cannot be expected after 30 hours.

As regards other options

  • Triacylglycerol synthesis cannot take place during conditions of starvation. Starvation is a state of catabolism. Glucagon the predominant hormone of this state, promotes adipolysis. Triacylglycerol synthesis takes place in the well fed state, in the presence of Insulin.
  • Increased insulin release is also incorrect, maximum insulin release occurs in the well fed state to promote utilization of glucose and to build up the body stores from the surplus nutrients. Under conditions of prolonged fasting as stated above, the insulin release is minimal, there is maximum release of glucagon to maintain blood glucose homeostasis.
  • Based on the similar concept of maintaining blood glucose homeostasis, decrease muscle protein breakdown during fasting is also inappropriate; there is rather a need for the constant supply of substrates of gluconeogenesis. Muscle protein breakdown can provide the carbon skeleton of amino acids, which can be further utilized for glucose production. The decreased insulin to glucagon ratio, and the decreased availability of circulating substrates, make this period of nutritional deprivation a catabolic state, characterized by initial degradation of glycogen, followed by degradation of triacylglycerol and protein.

Blood Glucose homeostasis (Summary)

Nutritional Status Source of blood glucose Cells using glucose as a fuel Major fuel of the brain
Well fed state Dietary glucose All cells Glucose
Post absorptive state Hepatic glycogenolysis (mainly) and gluconeogenesis All  cells except liver and skeletal muscle.

Adipose cells use at a reduced rate.

Fasting Hepatic  and renal gluconeogenesis and some hepatic glycogenolysis Brain cells and  the cells lacking mitochondria, Glucose and ketone bodies
Prolonged fasting / Starvation Gluconeogenesis (mainly) The cells lacking mitochondria Only ketone bodies


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