Question

You are a single molecule of glucose. Describe ALL of the anatomy that you would see, including transporters and pumps, as you travel from the afferent arteriole all the way to your reabsorption back into the kidney tissues. Second, describe all of the anatomy that you would see if your human had taken a sodium/glucose co-transport inhibitor.

Answer 1

Glucose Transport
Glucose transporters accomplish the movement of glucose from the extracellular space (deriving from the bloodstream) into cells. The reduction of glucose in the blood results from the action of insulin. Glucose enters the beta cells of the pancreas through the glucose transporter GLUT2 and this is a major signal leading to the release of insulin from these cells that reaches the bloodstream. Insulin in the blood is taken up through a transporter GLUT4, in adipose and muscle cells resulting in the reduction of blood glucose.

Sodium-glucose co-transporters (SGLTs)
SGLTs are expressed by cells in the small intestine and in the renal proximal tubules. These proteins mediate the active transport of glucose against an electrochemical gradient. Glucose in the intestinal lumen or the nephrons is transported against its concentration gradient by another transport mechanism, where glucose uptake is coupled with the uptake of sodium ions that are also being transported down their concentration gradient.

Facilitative glucose transporters (GLUTs)
The second group of glucose transporters, the GLUT family, is made up of 14 members. These are responsible for the bidirectional transport of glucose in tissues and cells. This involvesusing facilitative diffusion to carry glucose down a concentration gradient, into the cell.These proteins have one substrate binding site exposed to the inside of the cell and another exposed to the outside. Binding of glucose to one site induces a conformational change that results in glucose being transported from one side of the membrane to the other.

Transporter
SGLT
Tissues*
Renal tubules, intestinal epithelia (apical membrane)
Type of transport
Secondary active transport
Notes
Responsible for the absorption (intestine) and reabsorption (renal tubule cells) of glucose
Sensitive to insulin
No

Transporter
GLUT1
Tissues*
Pancreatic beta cells, hepatocytes
Type of transport
Facilitated diffusion
Notes
Pancreatic beta cells: important for gauging blood glucose levels in humans.
Hepatocytes: bidirectional transport of glucose when influenced by hormones, such as thyroid hormone.
Sensitive to insulin
No

Transporter
GLUT2
Tissues*
Pancreatic beta-cells, hepatocytes, intestinal epithelium, kidney

Type of transport
Facilitated diffusion
Notes
Hepatocytes: important for the bi directional transport of glucose with regards to hepatic glucose metabolism.
Sensitive to insulin
No

Transporter
GLUT3
Tissues*
CNS
Type of transport
Facilitated diffusion
Notes
Very high affinity for glucose.
Sensitive to insulin
No

Transporter
GLUT4
Tissues*
Skeletal muscle, cardiac muscle, adipose tissue
Type of transport
Facilitated diffusion
Notes
Expression regulated by insulin.
Sensitive to insulin
Yes

Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors. SGLT2 inhibitors are a class of prescription medicines that are FDA-approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes. Medicines in the SGLT2 inhibitor class include canagliflozin, dapagliflozin, and empagliflozin

Mechanism of Action
Sodium-glucose co-transporter-2 inhibitors work by inhibiting SGLT2 in the PCT, to prevent reabsorption of glucose and facilitate its excretion in urine. As glucose is excreted, its plasma levels fall leading to an improvement in all glycemic parameters
This mechanism of action is dependent on blood glucose levels and, unlike the actions of thiazolidinediones (mediated through GLUTs), is independent of the actions of insulin. Thus, there is minimal potential for hypoglycemia, and no risk of overstimulation or fatigue of the beta cells .Because their mode of action relies upon normal renal glomerular-tubular function, SGLT2i efficacy is reduced in persons with renal impairment.