When a person eats food, blood glucose levels increase. This stimulates pancreas to release insulin. Insulin in turn signals absorption of glucose by the muscle, liver and fat cells in the body. Insulin also stimulates the adipose tissues to take up glucose from blood. Glucose uptake by cells is promoted by the activation of glucose transporters embedded in the plasma membrane. Apart from the glucose required to meet the energy demands of the body, rest is stored as glycogen or fats. Glycogen and fats are long-term storage reserves for the body. They are broken down into simpler units, whenever body requires energy. On the other hand, insulin inhibits lipolysis. This stops hydrolysis of fats in the adipose tissues. Insulin also signals liver to stop synthesis of glucose (gluconeogenesis).
Insulin activates the enzymes pyruvate dehydrogenase (PDH) and acetyl CoA carboxylase (ACC). PDH converts pyruvate to acetyl CoA. This acetyl CoA is converted to malonyl CoA by ACC. This malonyl CoA provides the two-carbon backbone for further fatty acid synthesis (lipogenesis). Acetyl CoA synthesized by PDH also increases the flux through the lipogenesis pathway.
Insulin activates the enzyme pyruvate dehydrogenase phosphatase, which catalyses dephosphorylating of PDH. This leads to activation of PDH. Similarly, insulin activates PP2A phosphatase, which dephosphorylates ACC. This in turn activates ACC. At the transcription level, lipogenesis in the liver is managed by the transcription factor SREBP-1. Insulin as well as glucose promote expression of SREBP-1 mRNA levels in the adipocytes.
Errors with insulin regulation of blood glucose levels lead to diabetes. Type 1 diabetes is caused by the absence of production of insulin by the body. Type 2 diabetes is caused by poor response of insulin to increase in levels of blood glucose. In both cases, high amounts of glucose is left unused in the blood. Type 1 diabetes is countered by administration of commercially available insulin to the body. However, this may also cause excessive absorption of glucose for fat synthesis. This leads to weight gain.
Type 2 diabetes is often managed by lifestyle changes. This involves diet modifications and incorporation of exercise in the daily routine. Diet with portion control and requisite amount of carbohydrates is suggested. Physical activity allows use of the fat reserves for energy. This helps with weight management.
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