The Insulin Glucagon Ratio Determines Metabolic Status

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In most instances, insulin and glucagon produce opposing effects. Therefore, the net physiological response is determined by the relative levels of both hormones in the blood plasma, the insulin-glucagon ratio (I/G ratio).

I/G Ratio in the Fed and Fasting States. The I/G ratio may vary 100-fold or more because the plasma concentration of each hormone can vary considerably in different nutritional states. In the fed state, the molar I/G ratio is approximately 30. After an overnight fast, it may fall to about 2, and with prolonged fasting, it may fall to as low as 0.5.

Inappropriate I/G Ratios in Diabetes. A good example of the profound influence of the I/G ratio on metabolic status is in insulin-deficient diabetes. Insulin levels are low, so pathways that insulin stimulates operate at a reduced level.

However, insulin is also necessary for alpha cells to sense blood glucose appropriately,- in the absence of insulin, the secretion of glucagon is inappropriately elevated. The result is an imbalance in the I/G ratio and an accentuation of glucagon effects well above what would be seen in normal states of low insulin, such as in fasting.

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