Question

1. Provide a brief description of diabetes mellitus. Make sure you include

• The cause of this condition

• What effect this condition has on water balance in the kidneys

• The mechanism by which this condition produces its effect on the kidneys (be specific)

2. Provide a brief description of diabetes insipidus. Make sure you include

• The cause of this condition

• What effect this condition has on water balance in the kidneys

• The mechanism by which this condition produces its effect on the kidneys (be specific)

Answer 1

1. Diabetes mellitus (DM) is caused either by low production of insulin (Type I) or insulin insensitivity (Type II). In Type I DM, insulin production is decreased by beta cell of islets of Langerhans in the pancreas due to apoptosis and immune attack. In Type II DM, insulin cannot bind to insulin receptors on the target cells. Hence, there cannot be increase expression of glucose transporter or cause their translocation to the plasma membrane. Thus, glucose to the cell decreases and its levels increase in blood.

Diabetes mellitus causes increased filtration of glucose into kidneys. This causes the decreased reabsorption of glucose also by the proximal and distal convoluted tubules. Hence, in order to eliminate the excess glucose, there is increased secretion of water in order to produce more urine. Thus, DM patient will show frequent urination.

There is increased filtration of glucose from blood by the glomerulus into the filtrate as the levels of glucose increase in blood. The proximal and distal convoluted tubules will reabsorb only around 179 g/dm3 of glucose into blood. The remaining glucose will remain in the filtrate. This glucose can clog the capillaries in the kidneys. As a result, glomerular filtration will be affected. Protein will now enter the filtrate as the glomerular basement membrane is affected. This results in proteinuria and kidney nephropathy.

2. Diabetes insipidus causes loss of fluid as urine. There is no effect on glucose filtration or reabsorption in the kidney. It is a defect in water balance in the body.

It is caused by loss of in anti-diuretic hormone or vasopressin hormone secretion by anterior pituitary. ADH binds to V2 receptors in the collecting tubules of the kidneys. As a result, G protein signaling is increased, causing increased formation of cAMP. This leads to phosphorylation of AQP2 channels (aquaporin channels), which then translocate to the cell membrane. This leads to reabsorption of water into blood from lumen of collecting duct. In DI, there are no aquaporin channels in collecting duct due to ADH deficiency. Thus, water reabsorption is affected leading to loss of ADH secretion. Hence, water is lost in urine. As a result, the person becomes dehydrate and electrolyte balance in blood is also affected as sodium levels rise in blood.