gluconeogenesis
Gluconeogenesis is the body manufacturing sugar from scratch. When stored glycogen runs low during prolonged fasting, the liver (and to a lesser extent the kidney) builds brand-new glucose molecules out of non-carbohydrate raw materials — chiefly lactate, the amino acid alanine from muscle protein, and glycerol from fat. The name literally means “making new glucose.”
It is essentially glycolysis run in reverse, but with several irreversible steps bypassed by special enzymes such as PEPCK and glucose-6-phosphatase. Glucagon and cortisol promote it, while insulin suppresses it. This makes the liver a switchboard: a low insulin-to-glucagon ratio flips it toward glucose production, a high ratio toward glucose storage.
Gluconeogenesis is the slow, sustainable backup that keeps blood glucose adequate through long fasts when glycogen is exhausted. In type 2 diabetes, however, this process is often inappropriately active even after meals, and excessive hepatic glucose output is a major driver of fasting hyperglycemia — which is precisely what the drug metformin reins in.
Fat cannot be converted to glucose in net terms: the fatty-acid portion of triglycerides yields acetyl-CoA, which cannot become glucose in humans. Only the glycerol backbone of fat feeds gluconeogenesis — a key reason why prolonged fasting eventually breaks down muscle protein for substrate.