Phases of insulin secretion, and the effects of glucagon and glucocorticoids

Phase 1: Rapid secretion phase. After a latency period of 0.5 to 1.0 minutes, β cells receive glucose stimulation and exhibit a rapid secretion peak, which lasts for 5 to 10 minutes before weakening.

The second phase: the delayed secretion phase. A slow but persistent secretion peak that follows the rapid secretion phase, with its peak occurring approximately 30 minutes after stimulation.

Glucagon, also known as insulin-boosting hormone or anti-insulin, is a hormone secreted by the alpha cells of the pancreas, accompanying insulin secretion.

Unlike insulin, glucagon is a catabolism-promoting hormone. Glucagon strongly promotes glycogenolysis and gluconeogenesis, significantly raising blood glucose levels. Through the cAMP-PK system, glucagon activates phosphorylases in hepatocytes, accelerating glycogenolysis. Enhanced gluconeogenesis occurs because the hormone accelerates the entry of amino acids into hepatocytes and activates enzymes involved in gluconeogenesis. Glucagon also activates lipases, promoting fat breakdown, and simultaneously enhances fatty acid oxidation, leading to increased ketone body production. The liver is the target organ for these metabolic effects of glucagon; these effects disappear upon liver removal or by blocking hepatic blood flow.

In addition, glucagon can promote the secretion of insulin and somatostatin. Pharmacological doses of glucagon can increase the intracellular cyclic adenosine monophosphate (cAMP) content in cardiomyocytes, thereby enhancing myocardial contractility.

Adrenaline is the main hormone of the adrenal medulla. Its effects on blood vessels throughout the body vary not only in strength but also in their constriction or dilation. It constricts blood vessels in the skin, mucous membranes, and internal organs (such as the kidneys); and dilates blood vessels in the coronary arteries and skeletal muscles. Because it acts directly on the coronary vessels, causing vasodilation and improving blood supply to the heart, it is a fast-acting and potent cardiac stimulant. Adrenaline can also relax bronchial smooth muscle and relieve bronchospasm. Utilizing its effects of stimulating the heart, constricting blood vessels, and relaxing bronchial smooth muscle, it can alleviate symptoms such as weak heartbeat, low blood pressure, and difficulty breathing.

Glucocorticoids are a class of hormones secreted by the adrenal cortex, which regulate the biosynthesis and metabolism of carbohydrates, fats, and proteins, and also have anti-inflammatory effects. They are called glucocorticoids because their activity in regulating carbohydrate metabolism was the first to be recognized. Currently, the concept of glucocorticoids includes not only endogenous substances with the above characteristics and activities, but also many structurally optimized synthetic drugs with similar structures and activities. Glucocorticoid drugs are currently one of the most widely used classes of drugs in clinical practice.

Diabetes occurring during glucocorticoid use generally falls into two categories: first, pre-existing latent or clinical diabetes may develop or worsen after glucocorticoid treatment; second, it may be a purely adverse reaction to glucocorticoids, i.e., secondary diabetes. If the patient's condition permits, the dosage of glucocorticoids should be reduced as much as possible, and immunosuppressants should be added. In these patients, fasting blood glucose returns to normal after glucocorticoid dosage reduction or discontinuation. If the condition is active and glucocorticoid treatment is necessary, and fasting blood glucose and 2-hour postprandial blood glucose are high, diet should be controlled concurrently with glucocorticoid treatment, and hypoglycemic drugs such as insulin should be used in combination.

After eating, carbohydrates and other polysaccharides are digested and hydrolyzed into glucose, which is absorbed into the bloodstream. This directly stimulates pancreatic beta cells to produce insulin, which is then released into the bloodstream. Insulin in the blood can only function after binding to numerous insulin receptors on the surface of cells in the liver, muscles, and adipose tissue. Insulin transports glucose from the blood into cells for the body's use. Insulin is like a "key," and insulin receptors are like "locks"; only when the key is inserted can glucose enter the cells. Once inside the cells, glucose undergoes complex biochemical reactions to generate heat. A portion of this heat is directly supplied to various cellular activities, while the remainder is stored as energy, either synthesized into glycogen or fat, for later use.

In the regulation of blood glucose balance, an increase in insulin secretion inhibits the secretion of glucagon, while the secretion of glucagon promotes insulin secretion.

(1) Insulin lowers blood glucose levels when they rise, while glucagon raises them when they fall. They are antagonistic to each other.

(2) Increased insulin secretion inhibits glucagon secretion, which occurs when blood glucose concentration is already high. On the one hand, insulin secretion directly lowers blood glucose, and on the other hand, it indirectly lowers blood glucose concentration (after eating) by inhibiting glucagon secretion.

(3) Glucagon secretion promotes insulin secretion, which occurs when blood glucose concentration is already low. However, raising blood glucose depends on its utilization. For glucose to be utilized, it must enter cells, and whether glucose can enter cells depends on insulin. Insulin lowers blood glucose concentration because it promotes glucose entry into cells, further oxidizing and breaking down glucose, synthesizing glycogen, or converting it into fats, amino acids, etc. Therefore, glucagon secretion inevitably promotes insulin secretion.