Mechanisms of blood glucose metabolism: the coordination of the pancreas, islets of Langerhans, and insulin.

The pancreas is a gland with both endocrine and exocrine functions. The pancreas is covered by a thin connective tissue capsule, which extends into the gland, dividing the pancreatic parenchyma into numerous lobules. Within each lobule are numerous pancreatic acini and their ducts; this constitutes the exocrine portion of the pancreas, accounting for approximately 90% of its volume. The exocrine portion secretes pancreatic juice, which passes through the duodenum into the small intestine. Containing proteases, amylases, and lipases, pancreatic juice digests the three major nutrients: proteins, fats, and carbohydrates, and is the primary digestive fluid. An adult pancreas secretes 1000–2000 ml of pancreatic juice daily. Islets of Langerhans are clusters of endocrine cells scattered among the pancreatic acini, within the pancreatic parenchyma, with the highest concentration in the tail. They float within the pancreas like islands in the ocean, hence the name "islets of Langerhans." The islets of Langerhans constitute approximately 1.5% of the pancreas's volume and weigh about 12g. The human pancreas contains hundreds of thousands to over a million islets. Based on their staining and morphological characteristics, pancreatic islet cells are mainly divided into A cells, B cells, D cells, and PP cells. A cells account for about 20% of pancreatic islet cells and secrete glucagon; B cells account for about 75% of pancreatic islet cells and secrete insulin; D cells account for about 5% of pancreatic islet cells and secrete somatostatin; PP cells are few in number and secrete pancreatic polypeptide. The most important endocrine functions of pancreatic islets are the secretion of insulin and glucagon, which regulate blood glucose concentration. (1) Insulin: B cells are the main cells of pancreatic islets and are mostly located in the central part of the islets. B cells mainly secrete insulin, hence they are also called insulin cells. (2) Glucagon: A cells are mainly distributed in the peripheral part of the islets and secrete glucagon. Normal people secrete about 1 mg of glucagon per day. The concentration of glucagon in serum is 50-100 ng/L, and its half-life in circulation is 5-10 min. It is mainly inactivated in the liver, and the kidneys also have a degradation effect. Blood glucose refers to glucose in the blood. It is our body's most direct and primary source of energy, constantly being consumed and replenished. Therefore, blood glucose levels in healthy individuals remain relatively constant, ranging from 3.89 to 6.11 mmol/L on a fasting basis. Levels exceeding the upper limit of normal are called "hyperglycemia," while levels below the lower limit are called "hypoglycemia." Blood glucose originates from three main pathways: first, the digestion and absorption of carbohydrates from food in the gastrointestinal tract, which is the primary source; second, the breakdown of glycogen stored in the liver into glucose, which enters the bloodstream; and third, the conversion of non-carbohydrate substances in the liver (amino acids from protein breakdown, glycerol from fat breakdown, and lactic acid from muscle production) into glucose through gluconeogenesis under certain conditions. After a meal, carbohydrates in food are digested and absorbed into the bloodstream as glucose, causing a rapid rise in blood glucose concentration. This rise in blood glucose stimulates the pancreatic islet cells to secrete insulin, leading to a corresponding increase in blood insulin concentration. Insulin promotes the entry of glucose into tissues such as muscles, liver, and nerves for energy, while also converting unused glucose into glycogen or fat for storage. The combined effect of these two factors is to lower the elevated blood glucose concentration to the normal range, generally below 7.8 mmol/L within 2 hours after a meal. Under normal physiological conditions, the source and destination of blood glucose maintain a dynamic balance, thus the blood glucose concentration remains relatively constant, maintaining normal glucose metabolism in tissue cells. This relative stability is crucial for ensuring that various organs and tissues obtain energy, and is of great significance for ensuring the normal physiological activities of tissues and organs, especially the brain. Insulin is a protein hormone composed of 51 amino acids, with a molecular weight of approximately 6000, consisting of two amino acid peptide chains. The A chain has 21 amino acids, and the B chain has 30 amino acids. There are two disulfide bonds connecting the A and B chains. Insulin is the most important hypoglycemic hormone in the human body. B cells secrete an appropriate amount of insulin daily, which first enters the liver via the portal vein. 40%–50% of this insulin is broken down in the liver, and the remainder enters the bloodstream. The main physiological function of insulin is to bind to receptors on its target cells, promoting the entry of extracellular glucose into these cells to generate usable heat energy and convert it into glycogen for storage, while simultaneously inhibiting the re-breakdown of glycogen into glucose, thereby lowering blood glucose levels. In addition, insulin promotes glucose uptake by adipose tissue to synthesize fat, inhibits fat breakdown and ketone body production; it also promotes glucose uptake by muscles to synthesize muscle glycogen for energy storage and promotes muscle protein synthesis. Blood glucose levels are regulated by a variety of hormones, among which glucagon, adrenaline, and glucocorticoids have the effect of raising blood glucose, while insulin is the only hormone in the human body with the function of lowering blood glucose. Currently, all insulin used clinically is in injectable form and cannot be taken orally.