Diabetes mellitus – metabolism disturbance of: glycolysis, gluconeogenesis, glycogenolysis and glycogen synthesis, ketogenesis, ketonuria, glucosuria, osmotic diuresis, polyuria
The human body naturally tightly regulates blood glucose levels as a part of metabolism. The levels of glucose in the blood are monitored by Beta-Cells in the pancreas's Islets. They produce insulin, store it, and release it into the blood stream at appropriate times. If the blood glucose level falls to dangerous levels, the Alpha cells of the pancreas release glucagon, a hormone whose effects on liver cells act to increase blood glucose levels. They convert glycogen into glucose (this process is called glycogenolysis). The glucose is released into the bloodstream, increasing blood sugar levels. Insulin, causes the liver to convert more glucose into glycogen (this process is called glycogenesis), and cause muscle and fat tissue cells to take up glucose from the blood, thus decreasing blood sugar. Insulin also provides signals to several other body systems and is the chief regulatory metabolic control in humans. Only insulin reduces glucose levels, all others raise it (cortisol, ACTH, somatostatin, adrenaline)
Carbohydrates are broken down by the body into glucose, which is a form of sugar that is carried in the blood and transferred to cells for energy. In the cells it is phosphorylated into Glucose-6-Phosphate in order to preserve the concentration gradient so glucose will continue to enter the cells.
Diabetes: type 1 (insulin dependent) – pancreas doesn’t make enough insulin (mostly is young). Type 2 (insulin independent) – body cells develop resistance to insulin so don’t respond to it well, due to obesity in adults.
Insufficiency of insulin leads to:
- Increased glycogenolysis because of the missing suppressor effect of insulin on the glycogenolysis
- Increased capacity of gluconeogenesis
- Altered glycolysis and glycogen synthesis
This is due the suppressive effect insulin has on 4 key enzymes of gluconeogenesis is missing pyruvate carboxylase, phosphoenolpyruvate carboxylase, fructose-1-6-diphosphate and glucose-6-phosphate. Catabolic processes are increased due to the missing anabolic effect of insulin. Leading to hyperglycaemia.
Ketogenesis: Production of ketone bodies (from fatty acids). Due to increased lipolysis as insulin not present to supress (insulin sensitive lipase) causing build-up of acetylCoA. Also Kerb cycle enzymes suppressed due to lack of insulin Hence all the acetylCoA is redirected to ketogenesis leading to keto acidosis.
Ketonuria: high level of ketone bodies in urine. In diabetes or starvation, glucose not utilised properly so ketone bodies made as energy source, hence in urine