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Bulletin #16 – The Insulin-Glucagon Axis and the Control of Nutrient Partitioning

In Part I of this series we began ourdiscussion of endocrine physiology. I ex-plained that hormones play a central rolein nutrient partitioning. But what is nutri-ent partitioning? This is the process ofdetermining whether the food you eat endsup as muscle or fat or just gets burnedfor energy. The hormones chiefly respon-sible for this are insulin, glucagon, growthhormone, thyroid hormone, cortisol andepinephrine (adrenaline). In addition, tes-tosterone, aldosterone and prostaglandinE1 may also play a role. If this soundsmore like a boring medical lecture than anarticle about bodybuilding, consider thefollowing:1.  Muscle growth and fat loss arecontrolled almost entirely by these hor-mones. (Have I got your attention now?)You’re probably asking yourself, “But Ithought this was determined by diet andexercise?” Yes, diet and exercise do de-termine muscle growth and fat loss, butthese effects are mediated by hormones.Your diet and exercise habits set up a “hor-monal environment” inside your bodywhich determines if nutrients will bestored in the lean compartment or the fatcompartment. This is how nutrient parti-tioning works. Does this mean that ifsomeone injects growth hormone and in-sulin he can get lean and muscular with-out having to exercise? No, it doesn’t workthat way. Exercise is still required, forreasons we’ll explain in Part III of thisseries.2.

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If two groups of rats are fed andexercised the same, they weigh the same,just as you would expect. If one group isinjected with insulin, however, that groupbecomes very fat (1,2). Furthermore, ifanother group is injected with glucagon,those rats lose weight

[fat]  (2). Thesehormones, insulin and glucagon, are per-haps the most important factors in deter-mining body composition.3.  The composition of your diet (theamount of protein, carbohydrate and fat)seems to be as important as its caloriccontent in determining whether or not itwill make you fat (1). If your metabolicrate is around 2,000 calories a day, twothousand calories from pizza will tend tomake you fat. But 2,000 calories fromchicken, rice and broccoli will tend tomake you lean. Why? Because differentfoods have different effects on yourbody’s hormones which control energyusage and fat storage.4.  Over 90% of people who loseweight by caloric restriction return to theiroriginal weight within two years (1). Thisis because there is a weight regulatingcenter in your hypothalamus which triesto maintain a constant body weight. (Re-member from last month that the hypo-thalamus and pituitary gland together rep-resent the master endocrine gland of thebody, controlling all of your hormonal re-sponses.) It works like a “fat thermostat”by controlling your hunger level and yourbody’s metabolic rate (its rate of energyexpenditure).

These effects are mediatedby the nervous system and by hormonesand enzymes involved in fat metabolism.If you want to change your body weight,or your body composition, you have tochange the set point. The ratio of insulinto glucagon is perhaps the most impor-tant determinant of the set point (2) andwe’ll teach you how to control it in thisarticle.5.  We all know examples of over-weight people who starve themselves on1,000 calorie a day, only to remain fat.We also know that some bodybuilders eat6,000 to 8,000 calories a day and are ex-tremely lean and muscular. How can thisbe? Obese people are very rarely over-weight because they overeat, but ratherbecause the way they eat and their lackof exercise raise the set point and act tochannel calories to fat stores (1).  Thebodybuilders have learned how to chan-nel their calories to the lean compartmentand to minimize fat stores.This is what nutrient partitioning isall about.

At Parrillo Performance we’vebeen teaching people how to do it foryears. (We were doing it before it was in,as they say.) We’ve had great successhelping amateur and professional body-builders climb the ranks, and non-body-builders all over the country have usedthe same approach to lose weight perma-nently.So how do you get control of yourhormones and use this information to bea better bodybuilder? By careful controlof your diet and exercise habits. The mostimportant hormones involved in musclegrowth are growth hormone (whose ef-fect is largely mediated by the paracrine hormone IGF1), insulin and testosterone(3). The most important hormones in fatloss are insulin (lack of insulin, that is),epinephrine, growth hormone, glucagon,thyroid hormone and cortisol (3). Mostof these can be controlled by diet and ex-ercise and will fall within optimal levels ifyou follow our nutrition and training guide-lines.The best place to start in explainingthese hormones is with insulin and gluca-gon. As mentioned earlier, these hormonesare among the most potent determinersof fat storage and fat loss. Luckily for us,the levels of these hormones are entirelydetermined by diet, so we can control overthem by carefully regulating what we eat.Insulin and glucagon are both producedby the pancreas, but have exactly oppo-site effects. Their chief concern is theregulation of blood sugar (glucose) lev-els. Your brain requires a constant supplyof glucose for fuel, so the blood glucoselevel is tightly regulated to make sure thebrain never runs out of gas.When you eat carbohydrates they aredigested and absorbed by the small intes-tine and transported directly to the livervia the portal vein.

Essentially, all of thecarbohydrate you eat is converted to glu-cose by the liver before being released intothe bloodstream. After a meal your bloodglucose level rises as carbohydrates arereleased. This rise in blood sugar triggersa release of insulin from the pancreas.Insulin is required to help move glucoseinto cells by a process called “facilitatediffusion.” Once inside cells, the glucoseis burned for energy or stored as glyco-gen. Everything is fine so far. The prob-lem arises when carbohydrates are releasedinto the bloodstream too fast. This causestoo much insulin to be released. Wheninsulin levels get too high, some of thecarbohydrate is converted to fat insteadof being stored as glycogen. Also, if in-sulin levels get too high this actuallycauses too much sugar to be moved intocells. This results in “hypoglycemia,”which means low blood sugar. If yourblood sugar is too low you feel very tired.Simple sugars cause your blood sugar levelto spike, then paradoxically to decreaseto a lower level than before (because ofinsulin over-release).This is why the rate of digestion ofyour meals is important. On the Parrillodiet you stay away from foods contain-ing simple sugars (sweets, fruit, dairyproducts) and refined carbohydrates(bread and pasta) because these are re-leased into the bloodstream too fast, caus-ing too much insulin to be released.

Thischannels calories to fat stores—the op-posite nutrient partitioning we want. Thesefoods also have the effect of raising theset point—the amount of fat your hypo-thalamus programs your body to store(1).Combining protein and fibrous carbswith your starches, and avoiding simpleand refined carbohydrates, slows the re-lease of glucose into the bloodstream re-sulting in a lower, but longer, insulin re-lease. This gives you a uniform energylevel and channels calories toward muscleand away from fat.In summary, the most important roleof insulin is to regulate blood glucose lev-els. It does this by moving glucose intocells after a meal. It also increases the useof glucose for energy and increases gly-cogen stores. Too much insulin has theeffect of promoting fat storage.Glucagon is another hormone se-creted by the pancreas, but it has the op-posite effect of insulin. An increase inblood sugar triggers a release of insulinbut inhibits glucagon release.

Glucagon isreleased several hours after a meal whenblood sugar levels drop. Glucagon has theeffect of reducing glucose for energy andstimulating breakdown of body fat and theuse of fat for energy. Glucagon also stimu-lates the glycogen breakdown. The netresult of glucagon is to raise the glucoselevels back to normal and to signal thebody to begin using fat for energy sinceit’s running low on carbs. This is howthe insulin-glucagon axis acts to regulateblood sugar levels. Insulin decreases bloodsugar by moving glucose into the cells,stimulating glucose burning for energy andincreasing glycogen storage. Glucagonacts to increase blood glucose levels bystimulating glycogen breakdown, stimu-lating glucose synthesis (by a processknow as gluconeogenesis) and by shift-ing the metabolism from carb-burning tofat-burning.This is why you have to eat relativelymore carbohydrates during thegrowth season and reducecarbs during the pre-contestdiet. Insulin is an anabolic hor-mone, acting to stimulategrowth. Glucagon acts tostimulate fat loss.

The insulinto glucagon ratio is deter-mined entirely by the ratio ofcarbohydrate to protein inyour diet (3,4), so you cancontrol it exactly. Theinsulin:glucagon ratio is be-lieved to be one of the mostimportant factors (if not themost important factor) in de-termining your set point (2).The precise levels of proteinand carbohydrate to eat in or-der to optimize these hormones to maxi-mize muscle growth or fat loss are de-scribed in detail in the Parrillo Perfor-mance Nutrition Manual. First, you wantto meet your protein requirement by eat-ing 1.0 to 1.5 grams of protein per bodyof body weight per day. Next, limit fatcalories to 5% of your total daily caloricintake. Last, make up the remainder ofyour calories with a combination of carbs and CapTri. For weight loss, you gener-ally want to limit carb:protein ratio to1.0:1.5 and use more CapTri. For musclegain you will want to increase thecarb:protein ratio as well as increasing totalcalories.Of course, there is considerable bio-chemical variation among individuals. Hi-Protein Powder™ and Pro-Carb Pow-der™ are very useful tools for dialing inyour own body’s optimal insulin:glucagonratio. To gain lean body mass, meet yourbody’s protein requirement then slowlyadd in more Pro-Carb™ until you find theoptimal caloric level and insulin level foryour body to gain lean mass. To lose fatyou want to decrease carbs while in-creasing protein and CapTri®. Hi-Pro-tein™ and Pro-Carb™ are a convenientway for you to experiment and find howto optimize your body’s hormonal re-sponses. We’ve all had the experienceof going to the trouble of weighing ourfood and filling out our Diet Trac Sheetsonly to find out the numbers don’t workout right and we have to do it all overagain. Hi-Protein™ and Pro-Carb™ areperfect for adjusting your dietary intakefrom food to make your numbers workout right on your Diet Trac Sheets.One last thing about insulin. In addi-tion to it enhancing transport of glucoseinside cells, it is also required for trans-port of certain amino acids into cells.

These include the branched chain aminoacids (3), and this is why it is importantto take your Muscle-Amino Formula™with meals and not on an empty stom-ach. It has been found that neither insulinnor growth hormone alone is sufficientto stimulate growth—you have to haveboth of them together at the same time(3). This at least partly due to the factthat these two hormones act to transportdifferent sets of amino acids inside cells,and you need all of the amino acids presentat the same time in order for growth tooccur (3).How do insulin and glucagon exerttheir effects over carbohydrate and fatmetabolism? By activating or inhibiting thekey regulatory enzymes which carry outthese processes (5). Insulin acts to in-crease enzymes involved in the conver-sion of glucose to energy and enzymescarrying out glycogen synthesis, and toinhibit the enzymes of glucose synthesisand glycogen breakdown.[For those of you technically inclined,this means that insulin increases the ac-tivity of glucokinase and phosphofructoki-nase, which increases glycolysis (the firststage in the conversion of glucose to en-ergy). Insulin also decreases gluconeogen-esis—the synthesis of glucose from fromamino acids. Insulin increases the activ-ity of glycogen synthase, the key enzymeregulating glycogen synthesis, and inhib-its phosphorylase A, the enzyme respon-sible for glycogen breakdown.]Glucagon has the opposite effects.These two hormones act to stabilize bloodsugar levels—insulin by decreasing bloodsugar and glucagon by increasing bloodsugar.

These effects are brought about byexerting control over the enzymes regu-lating carbohydrate metabolism. Regard-ing fat metabolism, insulin acts to acti-vate the two most important enzymesregulating fat synthesis and storage. Glu-cagon inhibits these same two enzymes.In addition, glucagon initiates a cascadeof events resulting in mobilization of fattyacids from fat stores. The fats are thentransported to the muscles and used forenergy. This is why this information isimportant for bodybuilders.[Again, for those of you attuned tostrict biological terminology, glucagondecreases phosphofructokinase and gly-cogen synthase, which decrease glycoly-sis and glycogen synthesis, respectively.Glucagon also increases the activities offructose-1,6-biphosphatase and phospho-rylase, which increases gluconeogenesisand glycogenolysis, respectively.][Regarding fat metabolism, insulinacts to stimulate aceytl-CoA carboxylaseand lipoprotein lipase, the most importantenzymes regulating fat synthesis and stor-age, respectively. Glucagon inhibits thesesame two enzymes. In addition, glucagonactivates adenylate cyclase which initiatesa cascade of events resulting in mobiliza-tion of fatty acids from fat stores.The fats are then transported to themuscles and used for energy.]In summary, insulin acts to in-crease enzymes involved in the con-version of glucose synthesis, and toinhibit the enzymes glucose and gly-cogen breakdown.

Glucagon has theopposite effects. These two hor-mones act to stabilize blood sugarlevels—insulin by decreasing bloodsugar and glucagon by increasingblood sugar. These effects arebrought about by exerting controlover the enzymes regulating carbo-hydrate metabolism.By now you know that insulin is apowerful growth-promoting hormone —some people consider it the most power-ful anabolic hormone. Does this mean wewant to overeat carbohydrates or eatsimple sugars to get our insulin levels re-ally high? No, obviously not. Althoughinsulin is absolutely required for muscu-lar growth since it transports certain aminoacids inside cells, it is not very selectivein its actions. It promotes growth of fatcells as well as muscle cells (3,5). Wheninsulin levels get too high some of thecarbs “spill over” into fat stores.When dieting, do we want to go on azero-carb diet to minimize insulin andmaximize glucagon? No way. Under theseconditions muscle growth is impossiblebecause some of the amino acids cannotget inside cells (3). However, your bodycontinues to undergo a process called“obligatory protein loss,” which is theprocess of disposing of worn out proteins (Proteins are the machinery of the cell,and they get worn out like any other ma-chine.)

This amounts to the obligatory lossof proteins from the body at about therate of 30 grams per day, during starva-tion (3). When consuming a normal diet,these worn out proteins are simply re-placed, but this can’t happen if the aminoacids can’t get inside cells. So if you wanta sure way to lose lean mass, go on azero-carb diet. During a zero-carb diet thebody is in a very catabolic state, andbreaks down proteins to supply aminoacids which are converted to glucose,which the brain requires for fuel. Thismakes the problem even worse.Of course you want to adjust yourcarb:protein ratio, but moderation is thekey. Going to extremes is asking for di-saster. People have actually died from zero-carb diets even while getting plenty ofprotein, because they lost so much pro-tein from their heart muscle. In general,stick to the formula in the NutritionManual, as outlined above. That will putyou real close to optimal. Experiment withHi-Protein™ and Pro-Carb™ to find theperfect ratio for you. Learning to controlthe insulin-glucagon axis is one of the mostimportant aspects of nutrient partitioning,and it will take you a long way toward atop physique.


1. Remington DW, Fisher AG andParent EA. How to Lower your Fat Ther-mostat. Vitality House International,Provo, 1983.

2. de Castro JM, Paullin SK andDeLugas GM. Insulin and glucagon asdeterminants of body weight set point andmicroregulation in rats. J. Comp. Physiol.Psychol. 92: 571-579, 1978.

3. Guyton AC. Textbook of MedicalPhysiology. WB Saunders, 1991.

4. Westphal, SA, Gannon MC andNuttall FQ. Metabolic response to glucoseingested with various amounts of protein.Am. J. Clin. Nutr. 52: 267-272, 1990.

5. Mathews CK and van Holde KE.Biochemistry. Benjamin/CummingsPublishing Company, Redwood, 1990.

2018-03-13T11:10:39-04:00 May 12th, 2009|Technical Supplement Bulletins|

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