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How does a lack of insulin lead to high blood glucose in diabetes mellitus?

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An anatomical illustration of the human pancreas shows its location near the stomach and intestines, a detailed cross-section highlighting ducts and the islet of Langerhans, and an inset of pancreatic tissue histology with labeled alpha, beta, and delta cells. — diabetes mellitus The islets of Langerhans are responsible for the endocrine function of the pancreas. Each islet contains beta, alpha, delta, and pancreatic polypeptide (PP) cells that are responsible for the secretion of pancreatic hormones. Beta cells secrete insulin, a well-characterized hormone that plays an important role in regulating glucose metabolism.

In diabetes mellitus, a lack of insulin—or a decrease in its effectiveness—leads to high blood glucose, or hyperglycemia, through two primary mechanisms:12

Reduced Glucose Uptake: Under normal conditions, insulin triggers cells in muscle and adipose tissue to take up glucose from the bloodstream to be used for energy or storage. When insulin is absent or ineffective, these cells cannot efficiently absorb glucose, causing it to accumulate in the blood.32
Increased Glucose Production: Insulin normally acts on the liver to inhibit the production of glucose from non-carbohydrate sources (a process called gluconeogenesis) and to prevent the breakdown of stored glycogen. Without sufficient insulin, the liver continues to release glucose into the bloodstream even when it is not needed, further elevating blood sugar levels.341

As glucose levels rise, the body attempts to eliminate the excess sugar through the urine, which also draws out water and leads to common symptoms like increased thirst and frequent urination.2