Regulation of blood sugar

The regulation of blood sugar involves the hormone system, and several organs (pancreas, liver and kidney mainly). This regulation is part of the process of maintaining homeostasis within the body.

Normal fasting blood glucose in human is statistically between 0.80-1.10 g/L.

Glucose plays a vital role in the body: it is a catabolic substrate used (among others) for the operation of all of the cells of the body including the muscles, the brain and red blood cells. The regulation of blood glucose is controlled to maintain a constant energy supply to all bodies. It is regulated by insulin, glucagon, adrenaline, cortisol in times of stress, and growth hormone (the 4 last being insulin antagonists, they are called commonly “the counterregulation hormones”).

These hormones are primary messengers that bind on their receiver and activate, through various signal transduction cascades, the metabolic pathways involved in the regulation of blood glucose (catabolism and anabolism).

Role of the liver in the regulation of blood sugar

The role of the liver in the regulation of blood glucose was highlighted by the so-called experience “of the washed liver” by Claude Bernard in 1855.

Via the hepatic Portal vein, the liver receives power from glucose. One of its functions is to regulate blood sugar by synthesizing glycogen or lipid (fatty acids and glycerol) after input (meals), and release of glucose during fasting periods, so that the blood glucose remains constant and equal to its normal value (between 3.9 and 6.1 mmol/L; or between 0.8 and 1 g/L).

To do this, the liver regulates the production and storage of glucose through 3 metabolic pathways:

The glycogenesis is a synthesis of glycogen that allows storage of glucose in the liver as glycogen.

Glycogenolysis is a hydrolysis of glycogen that releases glucose and permits the storage of glucose as glucose-6-phosphate, by phosphorolysis of glycogen.

Gluconeogenesis is a pathway for the synthesis of glucose from elements non-glucoside as oxaloacetate and especially the alphacetoglutarate located at the crossroads between several metabolic pathways including those of certain amino acids so-called gluconeogenic. It is active by a decrease in blood glucose below its normal value associated with depletion of glycogen reserves and is necessary to the functioning of the brain and red blood cells. The kidney is also able to synthesize glucose.

Lipogenesis: the process of synthesis of fatty acids from glucose degradation product, acetyl-CoA. In human adipose tissue is not capable of this synthesis unlike other animals (in particular the rat).

Lipolysis: degradation pathway of fatty acids.

Role of the pancreas

In addition to pancreatic enzymes for digestion and released in the duodenal loop, the pancreas produces hormones (glucagon) hyperglycémiantes and hypoglycémiantes (insulin).

A partial removal of the pancreas (pancreatectomy) causes a very significant increase of blood glucose in the blood circulating since insulin no longer fulfills its role hypoglycemic.

Cells β of the islets of Langerhans of the pancreas produce insulin concentration of glucose and free fatty acids.

If severe hypoglycemia, the subject experiences a feeling of uncontrollable hunger (hunger). However, the variation of blood sugar is not the only factor triggering the sensation of hunger. The hunger/satiety ratio regulation pathways involve molecules (small peptides) produced by the digestive tract before and after feeding, molecules also involved (for part only) in the ways of regulating production of insulin and glucagon (hyperglycéminante hormone).

Role of the kidney

Apart from its néoglucoformatrice function, the kidney can secrete glucose if the circulating concentration is very high (diabetes mellitus), which does not occur in a healthy subject. normal glycosuria is void. Produced in primitive urine glucose is reabsorbed actively into the blood at the level of the proximal tubule. This function is saturable, which explains that beyond a concentration plateau (which corresponds to the circulating concentration of glucose equal to 9mmol/l approximately or 1.80 g/l), the surplus of this primitive urine glucose is more reabsorbed.

The kidney so, contributes to a lesser extent, to the maintenance of blood sugar.

Role of the nervous system

Parallel to this regulation that can be described of metabolic, other hormones may intervene in the regulation of blood glucose: adrenaline, cortisol, and growth hormone. Adrenaline is produced the médulo-adrenal, production increases stress, or effort. Acting on glycogenolysis, it causes an increase in blood sugar levels and allows a fast supply of glucose to the muscles in an effort. In the case of a strong emotional stress, cortisol is Hyperglycemic. Growth hormone is combined.

Hormone action

Depending on whether they are hyperglycémiantes or hypoglycémiantes, the hormones put at stake do not act in the same way or at the same time.

Insulin action

Insulin promotes the storage of glucose and decreasing its concentration in the blood: it is a hypoglycemic hormone.

At the level of its target cells (hepatocytes, adipocytes and muscle cells), insulin activates an enzyme, phosphatase, which results in the inactivation of the phosphorylase, responsible for the conversion of glycogen to glucose. Thus inactivated enzyme, glycogen is not hydrolyzed to glucose.

Insulin activates another enzyme, responsible for dephosphorylation of another enzyme, glycogen synthetase phosphatase, phosphorylated, is inactive. The latter leads to the synthesis of glycogen (glucose reserve commissioning).

These two phenomena increases the glycogen in the liver (promoting the glycogenesis, and by inhibiting glycogen breakdown).

In the body there are glucodépendantes cells and glucoindépendantes cells. The first cannot use glucose as energy substrate (such as neurons), second interchangeably use glucose and fatty acids. Insulin is at the level of the glucoindépendantes cells allowing them to express a carrier to glucose. Thus in the presence of insulin, these cells pump the glucose in the blood, in absence of insulin only glucodépendantes cells can capture blood glucose.

Action of glucagon and epinephrine

Glucagon is to target liver cells (especially) and adipocytes, muscle cells being devoid of glucagon receptor. (Medical Biochemistry has, Baynes, p 155-170)

Cells target of adrenaline are hepatocytes and muscle cells.

Glucagon and adrenaline, by setting on their receiver, activate Adenylate cyclase catalyzes the synthesis of cyclic AMP, the secondary Messenger.

It activates a protein kinase that catalyzes the phosphorylation of:

Phosphorylase kinase (active when it is phosphorylated), responsible for the phosphorylation of phosphorylase. The latter, active when it is phosphorylated, catalyzes the hydrolysis of glycogen to glucose.

Glycogen synthetase, inactive when it is phosphorylated, unable to catalyze the polymerization of glucose to glycogen.

These two phenomena lead to consumption (by promoting glycogenolysis and by inhibiting the glycogenesis) glycogen in the liver. There is therefore a release of glucose in the blood: glucagon and adrenaline are hormones hyperglycémiantes.

Action of cortisol

Cortisol is a hormone steroid combined, which is for fast extended (in the gluconeogenesis). It is a lipophilic, synthesized hormone in the fibrous layer of the cortico-adrenal.

It acts by binding to the receptor-protein complex HSP. This protein chaperonne is destroyed by the binding, and the complex can migrate to a particular sequence of DNA called HRE (element of response to the Hormone), which will allow cortisol to exercise its action of transcription of target genes.

Cortisol activates liver enzymes of gluconeogenesis, to produce glucose which will be released in the blood, increasing blood glucose. At the level of the adipose tissue, it will inhibit the entry of glucose and activate the lipolysis.

It promotes the production of glucose from substrates not carbohydrate, amino acid and oxidation of fatty acids via the formation of ketone bodies, to maintain a constant blood glucose.


Figure 1 shows a diagram of all of the actions of adrenaline, glucagon and insulin on blood glucose.

  • Regulation for hypoglycemia
  • Genetic aspects

The regulation of blood sugar seems to be linked only to a small number of genes (including a gene important for melatonin). An international study has shown that these few genes are also involved in the production of melatonin receptor (MT2) encoding. However this MT2 receptor is found in the retina, in the optic nerve, in the diencephalon area but also in the cells of the pancreas secrete insulin.

It was previously thought that melatonin was also involved in appetite (and perhaps in some cases of obesity), because injected into rats, it increases their food intake and weight.

In addition, a mutation in the gene encoding the receptor 2 (MT2) melatonin is associated with increased risk, obesity and type 2 diabetes but also to sleep disorders.

This discovery may explain some diabetes-depression associations. Patients with several mutations of these genes have a blood sugar of prediabetic type and are therefore more likely to develop diabetes and/or cardiovascular diseases early.

The genome of type 2 diabetes patients began to be systematically analyzed in 2007 after team CNRS / Imperial College London published a first diabetes genetic map. Shortly after, in 2008, French and English researchers demonstrated that the gene for glucose-6-phosphatase (an enzyme in the metabolism of glucose, pancreas specific) output strongly blood glucose.


Diabetes mellitus can be considered as an organic reliability issue: several hormones involved in the creation of sugars, but one, insulin, is hypoglycemic, able to supply sugar, making it essential for the regulation of blood sugar.

Clinical practice

Patients with type 1 diabetes must perform a hémoglucotest (HGT) to regulate their blood sugar. This test is performed by the staff of care at a hospital. It must first clean the part that will be tapped to not bias the results. It then bites on the side or medial of the last 3 fingers of the hand. It never bites in the pulp of the finger. Blood is deposited on the electrode and wait 20 seconds before the blood glucose of the patient. Based on the result it will then invest a certain dose of insulin to restore normal blood glucose levels. Patients with type 2 diabetes may also resort to injections of insulin after a decade on average.

Glucagon is used in injection of hypoglycemia demonstrations related to the use of insulin. It is not an antidote but to counter the effects of the insulin overdose.

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