As I understand it, both cortisol and glucagon cause an increase in blood sugar concentrations. However, I don't understand how they work differently or why they work separately. I would be very grateful if someone could explain the separate roles and functions of these two hormones and also the different effects that they have (I believe cortisol also has something to do with promoting lypogenesis in adipose tissue at the trunk of the body and lypolysis at the extremities).


3 Answers 3


Glucagon and cortisol are VERY different types of hormones, though each of them can affect glucose metabolism and effectively can increase glucose concentrations in the blood (albeit through different mechanisms).

Glucagon Peptide

Glucagon, pictured above, is a 31 amino acid peptide hormone (i.e. PROTEIN) that is released from the alpha-cells within the pancreatic islets. Glucagon travels through the blood and acts predominately in the liver on glucagon receptors. The glucagon peptide binds to the glucagon receptor on the OUTSIDE of the cell and transmits a signal to the INSIDE of the cell. This occurs when the glucagon binds to the receptor, changing its conformation or "shape" on the inside of the cell, which then causes binding and activation of a G-protein inside the cell ($G_S$). This $G_S$ protein activates an enzyme within the cell (adenylyl cyclase) to increase the concentration of a substance called cyclic AMP (aka cAMP) that activates a number of enzymes that ultimately increase the amount of glucose released by the liver. These effects are IMMEDIATE effects, which is why we sometimes give glucagon injections to treat patients with hypoglycemia (i.e. dangerously low blood sugar concentration). However, sustained glucagon signaling likely has effects on the expression of the enzymes that cause the glucose to be released from the liver as well (though that is a discussion for another question).


Cortisol, pictured above, is a steroid hormone (i.e. LIPID) that is released from the adrenal glands, specifically the zona fasciulata, which is the middle of the three 'layers' of the adrenal gland. Cortisol is referred to as a glucocorticoid and exerts its major effects through changing gene transcription in a variety of cell types. The way that cortisol does this is by binding its cortisol receptor, which is generally thought to be in the cytoplasm inside the cell. Upon binding of cortisol to the cortisol receptor, that complex is then transported into the nucleus of the cell where it binds DNA and can increase or decrease the transcription or expression of target genes. In the case of cortisol, these genes are for the enzymes that increase glucose production of the liver, and thus increase the body's capacity to maintain or elevate blood glucose. There is also some evidence that cortisol has additional effects independent of gene transcription, but that is outside the scope of this question. Regardless, the effects of cortisol on glucose metabolism are not immediate, but rather they take >30 minutes to several hours to begin to take effect.

As mentioned in the question, both glucagon and cortisol affect glucose metabolism. Cortisol also affects the transcription of a number of genes involved in adipose tissue and lipid metabolism, as well as genes that are involved in protein metabolism and inflammation. Cortisol can be injected into a patient with an autoimmune "flare-up" in order to quell the inflammation, but those are different mechanisms of cortisol than its effects on glucose metabolism. A description of those effects is also outside the scope of this question, but could easily be read about in recent reviews on cortisol available on PubMed, e.g. Recent Cortisol and Fatty Liver Review.

  • $\begingroup$ Good job on the molecular mechanisms. Is it really established though that the effect of cortisol on immune cell activity is distinct from its effect on glucose uptake and metabolism? Since activated immune cells are generally glycolytic, I thought the immunosuppressive effect of cortisol could be mediated by suppressing immune cell glucose uptake. $\endgroup$
    – Roland
    Dec 30, 2015 at 14:36
  • $\begingroup$ Thanks @Roland - the non-metabolic actions of glucocortioids isn't my area of expertise...but it appears that many other pathways (e.g. NF-kB and others) have been established that lead to the anti-inflammatory actions of cortisol and other glucocorticoids. See ncbi.nlm.nih.gov/pmc/articles/PMC3047790 and clinsci.org/content/94/6/557 $\endgroup$ Dec 30, 2015 at 17:06

Glucagon increase the blood sugar level in normal physiological pathway. It just mediate the blood sugar level when the level is too low.

On the other hand, cortisol is used when body under stress. It is used for "fight or flight" response in body, and it increases the energy production temporarily. When body is faced with stressor, the cortisol is secreted by a complex hormonal cascade, and the cortisol helps body to produce energy immediately to muscle and narrows the arteries to increase the heart rate, which force blood to pump harder and faster, and it also inhibits the activity of insulin. When body solves the problem, the hormone level return to normal.

Cortisol also can reduce the inflammation in the body, which can suppress the immune system.

Here is the paper maybe you will be interested. Cortisol — Its Role in Stress, Inflammation, and Indications for Diet Therapy


Good article, please allow me to comment:

Both hormones cortisol and glucagon are insulin-antagonistic (=anti-insulin hormones).

Glucagon differs from cortisol because it is a peptide hormone and cannot cross cell membrane. It must be injected like insulin. Glucagon is released from α-Langerhans cells in the pancreas during the acute stage of hypoglycemia and counters insulin directly by reversing/suppressing glycogen synthesis and converting it to glycogeno-lysis (=release of glucose from glycogen). Glucagon may be used by type 1 diabetics to treat insulin shock/coma (severe hypoglycemia caused by excess insulin). Cortisol is steroid hormone. It crosses cell membrane abd binds to its nuclear receptor. Cortisol is more complex than glucagon:

1 - Cortisol regulates other glucose-regulatory hormones including glucagon and epinephrine synthesis. The synthesis of epinephrine (adrenaline) from nor-epinephrine requires cortisol in the last step which SAME is involved.

2 - Cortisol is also involved in gluconeogenesis, the synthesis of glucose from muscle protein and other non-carbohydrates in order to sustain the brain during fasting and starvation

3 - Cortisol antagonizes insulin. Evidence exist that excess cortisol can cause diabetes while deficiency of cortisol can lead to higher insulin sensitivity and hypoglycemic syncope as seen in Addison disease. Death may occur from adrenal crisis if Addison disease left untreated.


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