Role of Insulin in Diabetic ketoacidosis

Case details

An 8-year old boy, a known diabetic (type 1 DM), has been brought to emergency room in a state of coma. His breathing is rapid and deep, and his breath has a fruity odor. His blood glucose is 480 mg/dL. The attending physician has administered IV fluids, insulin, and potassium chloride. A rapid effect of insulin in this situation is to stimulate

A. Gluconeogenesis in liver

B. Fatty acid release from adipose

C. Glucose transport in muscle

D. Ketone utilization in the brain

E. Glycogenolysis in the liver

Answer- The right answer is- c) Glucose transport in muscle.

The child is suffering from diabetic ketoacidosis, the commonest complication of Type 1 diabetes mellitus. Fruity odor of breath is due to the presence of acetone, one of the ketone bodies (the other two are acetoacetate and beta hydroxy butyrate). Acetone is excreted through lungs. High blood glucose is due to non utilization or extra synthesis of glucose in the presence of reversed insulin to glucagon ratio.

In the conditions of non utilization of glucose, fats are alternatively oxidized to provide energy. The extra Acetyl co A produced by fatty acid oxidation is diverted to the pathway of ketogenesis.

As regards other options-

Insulin does not promote gluconeogenesis, rather it inhibits it.

Similarly fatty acid release from adipose tissue (adipolysis) is an action of glucagon and catecholamines, insulin inhibits this action also.

Ketone utilization in brain is also not the correct option. By promoting glucose utilization, insulin inhibits ketosis; in fact ketosis occurs only when glucose is not available for utilization as in starvation, low carbohydrate/high fat diet, or diabetes mellitus.

Glycogenolysis is also not the correct answer. Insulin promotes glycogenesis, it is an anabolic hormone, and it prevents all the catabolic processes including glycogenolysis.

In diabetic ketoacidosis, Insulin promotes glucose uptake through GLUT4 transporters (figure) in skeletal, cardiac muscle and adipose tissue. It also promotes glucose utilization by stimulating the enzymes of pathways of glucose utilization.

IV fluids are given to treat dehydration as DKA is mostly associated with polyuria. Potassium chloride is given to maintain potassium balance.

GLUT-4

Figure- Insulin increases the number of GLUT4 transporters present on the surface of adipose, cardiac and skeletal muscle cells, as a result glucose update is increased in these cells. GLUT-4 are the only transporters that are under the control of insulin.

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