The mechanism that keeps the concentration of glucose in the blood, or blood glucose level, constant is a typical example of homeostasis. When this mechanism is disrupted, diabetes develops.
Basic Knowledge
The normal fasting blood glucose level is about 70〜100 mg/dL. It temporarily rises after a meal but soon returns to normal through regulatory mechanisms.
When blood glucose rises (after a meal, for example):
① The hypothalamus detects it and stimulates the B cells of the pancreatic islets of Langerhans through the parasympathetic nerves.
② Insulin is secreted.
③ Insulin acts on cells in various tissues, causing them to take up glucose (muscles and fat), synthesize glycogen in the liver, and promote fat synthesis.
④ As a result, blood glucose decreases.
When blood glucose falls (during fasting or exercise, for example):
① The hypothalamus detects it and stimulates pancreatic A cells and the adrenal medulla through the sympathetic nerves.
② Glucagon is secreted from pancreatic A cells, and adrenaline is secreted from the adrenal medulla.
③ Glycogen is broken down in the liver, and glucose is released into the blood.
④ If the condition continues for a long time, the adrenal cortex secretes glucocorticoids, which promote gluconeogenesis from proteins.
⑤ As a result, blood glucose rises.
Thus, only one hormone lowers blood glucose—insulin—whereas several hormones raise it: glucagon, adrenaline, and glucocorticoids. This is thought to be because excessive lowering of blood glucose stops brain function, since glucose is the brain's main fuel. Therefore, the mechanisms that raise blood glucose are redundant.
Blood glucose level (the concentration of glucose in the blood; normal fasting level 70〜100 mg/dL)
Islets of Langerhans (endocrine tissue in the pancreas; A cells and B cells)
B cells (secrete insulin; blood glucose↓)
A cells (secrete glucagon; blood glucose↑)
Glycogen (the storage form of glucose stored in the liver and muscles)
Gluconeogenesis (the pathway that produces glucose from amino acids, fats, and other substances)
Diabetes (a condition of chronically high blood glucose; type I and type II)
Further Study
Insulin is a small peptide hormone consisting of 51 amino acids. Its A chain (21 residues) and B chain (30 residues) are linked by disulfide bonds (S-S bonds). In pancreatic B cells, it is first produced as proinsulin; the C-peptide is then removed to form mature insulin. In 1921, Banting and Best extracted and isolated insulin from the pancreas of dogs and put it into practical use as a diabetes treatment. This historic achievement earned them the Nobel Prize the following year, in 1923.
When insulin binds to the insulin receptor on the cell membrane, a receptor tyrosine kinase, intracellular signaling pathways are activated. The glucose transporter GLUT4 moves to the cell membrane and takes glucose into the cell. Abnormalities in this pathway are central to type II diabetes (insulin resistance).
Two types of diabetes:
・Type I diabetes: Pancreatic B cells are destroyed by an autoimmune response, so insulin cannot be produced. It often begins at a young age. Insulin injections are essential.
・Type II diabetes: Caused by lifestyle factors (obesity and lack of exercise) and insulin resistance. More than 95% of diabetes cases in Japan are type II. In addition to diet and exercise therapy, metformin, SGLT2 inhibitors, and GLP-1 agonists are used.
Diabetes causes serious complications. The three major complications are diabetic retinopathy (a cause of blindness), nephropathy (a cause of dialysis), and neuropathy. It also increases the risk of myocardial infarction and cerebral infarction. In Japan, more than 10 million people have diabetes, making it an important lifestyle-related disease.
Recently, GLP-1 agonists such as semaglutide have attracted attention for both diabetes and obesity treatment. GLP-1 is an incretin hormone secreted by the intestine. It promotes insulin secretion and suppresses appetite. Chemically synthesized, long-acting GLP-1 agonists have also attracted great attention in the pharmaceutical market.
- Normal blood glucose = fasting 70〜100 mg/dL
- Only insulin lowers blood glucose
- Hormones that raise blood glucose = glucagon・adrenaline・glucocorticoids
- High blood glucose sensor = parasympathetic nerves→B cells→insulin
- Low blood glucose sensor = sympathetic nerves→A cells・adrenal glands→glucagon・adrenaline
- Type I = autoimmune disease・young age・insulin injections essential
- Type II = lifestyle factors・adults・most diabetes cases
- Three major complications = retinopathy・nephropathy・neuropathy
Points to Note
① Do not confuse insulin (lowers blood glucose) with glucagon (raises it). Both come from the pancreatic islets of Langerhans, but their cells differ: B cells produce insulin, and A cells produce glucagon. ② Type I diabetes (autoimmunity, insulin depletion, young age) and type II diabetes (lifestyle factors, insulin resistance, middle or older age) have different causes and treatments. ③ Gluconeogenesis is the pathway that produces glucose from substances other than carbohydrates, such as amino acids and lactate. It occurs in the liver. ④ Several hormones raise blood glucose, but only one hormone—insulin—lowers it. This is also why failure of insulin action leads to diabetes.
Practice
- What hormone is secreted by B cells in the pancreatic islets of Langerhans?
- Name three hormones that raise blood glucose.
- What type of diabetes is caused by autoimmune destruction of pancreatic B cells?