Almighty Glucagon!

TAGS: glucogen, Jamie Hale, fat, hormone

Jay Robb, author of The Fat Burning Diet, says:

“In place of insulin, your body will secrete a powerful hormone called glucagon, which will mobilize fatty acids and begin laying the ground work for some serious fat burning activity. And no hiding places can elude the ‘eagle eyes’ of the almighty glucagon! Cellulite (rhymes with the smell of your feet) doesn’t stand a chance against the triglycerides’ torching power of glucagon. Nor do double chins, love handles, beer bellies, bubble buns, lumpy legs, or thunder thighs.”

Is glucagon really the chief fat burning hormone? Glucagon is a hormone that is synthesized and secreted by the alpha-2 cells of the pancreatic islets of Langerhans. Glucagon is composed of 29 amino acids arranged in a single polypeptide chain. It maintains blood glucose levels by activating hepatic glycogenolysis and gluconeogenesis.

The alpha cell is responsible for a variety of stimuli that signal actual or potential hypoglycemia. Glucagon secretion is increased by low blood glucose, amino acids, and epinephrine.

Glucagon secretion stimulation

The primary stimulus for glucagon release is low blood glucose. Elevated glucagon levels prevent hypoglycemia (assuming there’s a sufficient amount of liver glycogen to provide glucose to the bloodstream).

Amino acids are derived from a meal containing protein. They stimulate the release of both glucagon and insulin. The amount of the hormone stimulated depends on the individual amino acid and/or the group of amino acids present. A study by Kuhara and colleagues (1991) examined the effects of the intravenous infusion of 17 amino acids on the secretion of insulin, glucagon, and growth hormone (GH) in six castrated male sheep. Leucine was the most effective amino acid in stimulating insulin secretion but did not produce any increase in glucagon and GH secretion. Alanine, glycine, and serine induced a greater enhancement of both glucagon and insulin secretion than other amino acids. No amino acid was able to specifically stimulate glucagon secretion without also increasing insulin or GH secretion. Branched-chain amino acids tended to suppress glucagon secretion and enhance insulin.

A study by Calbet and colleagues (2002) was conducted to find whether the hormonal response to feeding with protein solutions is influenced by the nature and degree of protein fractionation. Insulin and glucagon responses after intake of protein solutions containing the same amount of nitrogen (2.9 grams each) in three men and three women were investigated. Four test meals (600 mL) [glucose (419 kJ/L), pea (PPH) and whey peptide hydrolysates (WPH) (921 and 963 kJ/L, respectively), and a cow’s milk solution (MS) containing complete milk proteins (2763 kJ/L)] were tested. Despite the higher carbohydrate content of the MS, the peptide hydrolysates elicited a peak insulin response that was two and four times greater than that caused by the MS and glucose solutions. The insulin response was closely related to the increase in plasma amino acids, especially leucine, isoleucine, valine, phenylalanine, and arginine. The three protein solutions elicited similar increases of plasma glucagon, although the response was fastest for both peptide hydrolysates and more prolonged for the MS. The glucagon response was linearly related to the increase in plasma amino acids, regardless of the rate of gastric emptying or meal composition. Among the plasma amino acids, tyrosine and methionine were most closely related to the plasma glucagon response.

Rocha and colleagues (1972) studied the effects of 20 amino acids on pancreatic glucagon secretion in conscious dogs. Pancreatic glucagon and insulin were measured by radioimmunoassay. Seventeen of the 20 amino acids caused a substantial increase in plasma glucagon. Asparagine had the most glucagon-stimulating activity (GSA) followed by glycine, phenylalanine, serine, aspartate, cysteine, tryptophan, alanine, glutamate, threonine, glutamine, arginine, ornithine, proline, methionine, lysine, and histidine. Only valine, leucine, and isoleucine failed to stimulate glucagon secretion. Isoleucine may have actually reduced it.

The release of glucagon is stimulated by increased concentrations of either circulating epinephrine, which is produced by the adrenal medulla; norepinephrine, which is produced by sympathetic innervation of the pancreas; or both. During periods of stress, trauma, or severe exercise, the elevated epinephrine levels can override the affect of the alpha cell of circulating substrates. Under these conditions, regardless of the concentration of blood glucose, glucagon levels are elevated in anticipation of increased glucose use. Glucagon secretion is significantly decreased by elevated blood glucose and insulin.

Metabolic effects

The intravenous infusion of glucagon leads to an immediate rise in blood glucose. This is due to an increase in the breakdown of liver glycogen and an increase in gluconeogenesis. Glucagon stimulates the hepatic oxidation of fatty acids and the formation of ketone bodies from acetyl CoA. The lipolytic effect of glucagon in adipose tissue is minimal in humans. Let me repeat that sentence—the lipolytic effect of glucagon in adipose tissue is minimal in humans.

Glucagon increases the uptake of amino acids by the liver, resulting in increased availability of carbon skeletons for gluconeogenesis. Glucagon binds to high affinity receptors on the cell membranes of the hepatocyte. The receptors for glucagon are different from those that bind epinephrine or insulin. Glucagon binding results in the activation of adenylyl cyclase in the plasma membrane. This causes a rise in cAMP (the second messenger), which activates cAMP-dependent protein kinase and increases the phosphorylation of specific enzymes or other proteins.

Many bodybuilding coaches promote the idea that insulin secretion should be minimized and glucagon secretion should be maximized pre-competition. With that idea in mind, the suggestion of BCAA supplementation (by the truckloads) is often advised. This seemingly contradictory advice brings up the question do these coaches have any idea why they promote unfounded claims?

A study was conducted by Gravholt and colleagues (2001) to determine whether glucagon stimulated lipolysis in adipose tissue. The researchers found that high glucagon levels did not increase interstitial glycerol (and thus lipolysis) in adipose tissue. Jensen and colleagues (1991) conducted a study to determine whether physiological changes in plasma glucagon concentrations are important in regulating basal adipose tissue lipolysis. The researchers found “…changes in plasma glucagon concentrations within the physiological range have little or no effect on adipose tissue lipolysis.”


  • Glucagon stimulates liver phosphorylase and promotes liver glycogen breakdown and gluconeogenesis.
  • In the primary steps in adipose tissue burning, triglyceride is mobilized, which refers to the breakdown to TG to three fatty acids and a glycerol molecule. Glycerol is released, sent to the liver, and regenerated to glucose. The breakdown of TG occurs due to hormone sensitive lipase (HSL), which is primarily influenced by insulin and the catecholamines.
  • Adrenaline and nor-adrenaline bind to beta-adrenergic receptors in fat cell stimulating HSL, causing FFA release. Triglyceride breakdown is facilitated by three enzymes—triacylglycerol lipase, diacyclglycerol lipase, and monoacylglycerol lipase.
  • Once broken down, FFAs travel through the bloodstream to the liver or muscle. FFA is taken up into the muscle and transported into mitochondria via carnitine palmityl transferase 1 (CPT-1). FFAs are also broken down in the liver. FFAs are burned in mitochondria to produce ATP and acetyl-CoA.


  • Hale J. Fat Burning: How it Works. From: # Accessed: September 15, 2010.
  • Hale J (2007) Knowledge and Nonsense: The Science of Nutrition and Exercise. MaxCondition Publishing.
  • Robb J (1994) The Fat Burning Diet. Loving Health Publications.
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