Glucagon: Insulin's Counterpart in Fasting, Protein Meals and Type 2 Diabetes

Glucagon is a hormone released by the alpha cells of the pancreas. Its main job is the reverse of insulin's: when blood glucose drifts down, glucagon tells the liver to release glucose so that the brain is never short. It rises between meals, overnight and in a fast, and it also rises after a protein meal. In type 2 diabetes it stays high when it should fall, and a study of Indian men with newly diagnosed diabetes found fasting glucagon of 83.8 pg/ml against 65.6 pg/ml in men without the condition. This entry belongs to NNWA's handbook of hormones.

What does glucagon do in the body?

It raises blood glucose by acting on the liver. The pancreas releases more glucagon as blood sugar falls and less as it rises, and the liver answers by breaking down its stored carbohydrate and by building new glucose from amino acids and other small molecules. Glucagon also increases the liver's production of ketones, the fuel made from fat during long gaps without food. A review marking a century since its discovery in late 1922 adds that it also shapes how the liver handles amino acids and fats.

The handbook entry on insulin describes the other half of the pair. Insulin is the signal of the fed state and moves glucose into tissues; glucagon is the signal of the unfed state and moves glucose out of the liver. Neither is good or bad, and the brain's steady supply of fuel, described in the entry on glucose, depends on the shift between them.

How does glucagon work between meals and overnight?

As the last meal is absorbed, insulin falls and glucagon's message to the liver takes over. The liver holds roughly 80 g of glucose as glycogen, and that store is used to keep topping up the 4 g or so of glucose that circulates in the blood at any moment. The liver also makes new glucose, and that share grows the longer the gap lasts, which is why you wake with blood glucose in the usual range.

What happens to glucagon in a longer fast?

It climbs for about three days and then eases back. In a classic study of prolonged fasting, with fasts lasting up to six weeks, plasma glucagon rose twofold to a peak on the third day and then declined to a level at or above the usual overnight value, while insulin fell to a plateau by the third day.

A second study measured liver glycogen directly with magnetic resonance during a 68-hour fast. New glucose production supplied 64 per cent of the body's glucose during the first 22 hours, 82 per cent in the next 14 hours and 96 per cent in the 18 hours after that. For a healthy adult keeping an Ekadashi or Navratri fast this is reassuring physiology, not a weight-loss method. People on glucose-lowering medicines are a different case, covered in the piece on fasting with diabetes.

Why does a protein meal raise glucagon?

Because amino acids stimulate insulin, and glucagon is released alongside to stop blood glucose from dropping. A plate of paneer, egg, fish or dal with little carbohydrate still calls for insulin, and unopposed insulin would pull glucose down. In an experiment on dogs in 1969, an amino acid infusion lowered glucose by an average of 3 mg per 100 ml when glucagon was free to respond and by 35 mg per 100 ml when its release was suppressed.

Human studies agree. When six adults drank different protein solutions, the glucagon response followed the rise of amino acids in the blood in a straight-line relationship, whatever the protein source. When eight healthy adults took repeated whey protein drinks, insulin reached about six times its basal level and glucagon about eight times, glucose leaving and entering the blood both rose by roughly 25 per cent, and blood glucose stayed normal.

None of this is a reason to eat more or less protein than you need. The fuller list sits in the protein table for Indian foods, and the protein calculator turns body weight into a daily figure.

ICMR-NIN's position: no requirement is set for a hormone in India

Glucagon is made by the body, so there is no dietary requirement for it and no food contains a useful amount. What ICMR-NIN's 2020 report does set are the intakes that keep the insulin and glucagon system supplied with raw material. The figures below are for healthy adults; pregnancy, kidney disease and diabetes need individual advice.

What is glucagon's role in type 2 diabetes?

In type 2 diabetes glucagon is too high for the blood glucose that accompanies it. A study that sampled blood hourly across eight hours and two meals found glucagon higher than normal in both lean and obese patients, and the day's glucagon tracked the day's glucose, with a correlation of 0.57. A later experiment in ten patients showed where the fault appears: glucagon fell normally when glucose was given into a vein, but failed to fall when the same glucose was swallowed.

How much weight to give this is still argued. Two senior researchers proposed in 2012 that glucagon excess, more than insulin lack, is the essential feature of diabetes; the centenary review is more cautious and says the raised glucagon has been proposed to contribute to high glucose. A 2019 review connects it to the liver: fat in the liver may blunt glucagon's action on amino acids, amino acids then rise in the blood, and they push the alpha cells to release more glucagon. Its authors describe that chain as emerging.

The Indian picture: glucagon, the waist and the liver

ICMR-INDIAB, the national survey of 113,043 adults, put diabetes at 11.4 per cent and prediabetes at 15.3 per cent, with abdominal obesity in 39.5 per cent. Glucagon has been measured in Indians too. Researchers in north India studied 81 non-obese men, with a BMI below 25, who had been diagnosed with type 2 diabetes within the past year, and 30 non-obese men without it. Fasting glucagon averaged 83.8 pg/ml in the first group and 65.6 pg/ml in the second, and the values after a meal were 80.2 and 64.1 pg/ml.

Within the diabetes group, men who also had fatty liver had higher fasting glucagon (85.9 pg/ml) than those who did not (81.0 pg/ml). Waist to hip ratio and fat deep in the abdomen were among the four measures that predicted fasting glucagon. This was one clinic-based study of men, so it shows an association, not a cause. The waist to hip ratio calculator and the guide to a fatty liver diet in India take those two threads further.

Which tests involve glucagon, and who orders them?

The glucagon blood test measures the hormone in a blood sample, sometimes after fasting, and it is not part of routine diabetes care. The United States National Library of Medicine lists low blood sugar as the most common reason for ordering it, followed by rarer ones such as a suspected glucagonoma, a tumour of the pancreas that produces the hormone, cirrhosis and pancreatitis. Diabetes itself is diagnosed and followed on glucose tests and HbA1c.

That source gives a normal range of 25 to 50 pg/mL and adds that ranges vary between laboratories. The Indian study above shows how much: its healthy comparison group averaged 65.6 pg/ml on a different assay. A glucagon value therefore means little without the laboratory's own range, the timing of the sample and the clinical question, and reading it is the work of the doctor who asked for it, usually an endocrinologist. No diet should be started, stopped or judged on a glucagon number.

A worked example: one night and one paneer dinner

This is an illustrative case to show the arithmetic. It is not a real person and not a meal plan. A 45-year-old vegetarian schoolteacher in Pune, weighing 60 kg and with no diabetes, finishes dinner at 8.30 pm and eats breakfast at 8.30 am. She has read that paneer raises a hormone that raises sugar, and wonders whether to drop it.

Common myths and mistakes about glucagon

A second mistake is to treat the protein effect as a reason to fear dal, paneer or eggs. In healthy adults the rise in glucagon after protein arrived with a rise in insulin and left blood glucose unchanged. A third is to ask a laboratory for a glucagon level out of curiosity, when the result cannot be read without a clinical question.

Glucagon as a medicine, low blood sugar, and when to see a doctor

Glucagon is also a prescription medicine. It is used as an emergency injection for severe low blood sugar and, in hospitals, to still the gut during certain X-ray tests. It works by making the liver release its stored sugar. Whether someone should keep it at home, and how it is used, is decided and taught by the treating doctor; nothing here is guidance on its use. The glucagon response to low blood sugar can also fail: in a 1973 study, glucagon did not rise during insulin-induced hypoglycaemia in six people with juvenile-onset diabetes, while it rose in the comparison group.

ICMR's 2018 guideline on type 2 diabetes calls hypoglycaemia a common side effect of treatment, especially with sulphonylureas and insulin, and lists hunger, sweating, tremors and palpitation as the classical symptoms, with or without loss of consciousness. If you take such medicines, do not fast, skip meals, cut carbohydrate sharply or change a dose on your own. Agree the plan with your prescriber first. Food and activity work beside treatment, and the person responsible for the prescription adjusts it.

Can food or fasting correct high glucagon?

No food, fast or supplement has been shown in the sources read here to normalise glucagon in type 2 diabetes, and no claim of that kind should be believed from a label. What the evidence supports is indirect. Glucagon in the Indian study rose with waist to hip ratio and liver fat, so the habits that reduce both are the reasonable place to work. Some prescribed diabetes medicines lower glucagon as part of their action, which is explained in the entry on the gut hormone GLP-1. Compounds that block glucagon directly have lowered fasting glucose in research but remain under development.

Learning this with NNWA

NNWA is a private skill academy based in Kolkata that teaches online, in English and in Hindi. Courses such as the Diabetes Nutrition course train people to coach healthy clients on meals, fasting gaps and activity and to send medical cases to a doctor. No NNWA course is a degree, and none makes its holder a dietitian.