WBR0936

Author	PageAuthor::William J Gibson
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::Endocrine, SubCategory::Musculoskeletal/Rheumatology
Prompt	[[Prompt::A scientist is studying the mechanism of exercise-induced insulin sensitivity in diabetic patients. A biopsy of the vastus lateralis muscle is obtained from the left leg at rest. 3-6 weeks later, the subjects performed 45-60 minutes of cycling at 70% VO2 max, and immediately thereafter a biopsy was obtained from the right vastus lateralis muscle. The investigator performs immunohistochemistry of the obtained tissues. Which of the following will demonstrate increased localization to the plasma membrane?]]
Answer A	AnswerA::GLUT1
Answer A Explanation	AnswerAExp::Incorrect: GLUT1 is expressed in erythrocytes and the brain. It does not translocate to the cell membrane with exercise.
Answer B	AnswerB::GLUT2
Answer B Explanation	AnswerBExp::Incorrect: GLUT2 is a bidirectional glucose transporter that is expressed in pancreatic islet cells, the liver and the kidney. It does not translocate to the cell membrane with exercise.
Answer C	AnswerC::GLUT3
Answer C Explanation	AnswerCExp::Incorrect: GLUT3 is primarily expressed in neurons and does not translocate to the cell membrane with exercise.
Answer D	AnswerD::GLUT4
Answer D Explanation	AnswerDExp::Correct: GLUT4 is an insulin-responsive glucose transporter found in adipose tissue and muscle that translocates to the cell membrane upon exercise.
Answer E	AnswerE::GLUT5
Answer E Explanation	AnswerEExp::Incorrect: GLUT5 is a fructose transporter expressed on the apical border of enterocytes in the small intestine. It does not translocate to the cell membrane with exercise.
Right Answer	RightAnswer::D
Explanation	[[Explanation::Glucose is a charged molecule that requires transporters to enter cells. The glucose transporters found in various cell types in the body are differentially expressed and regulate glucose uptake differently. GLUT4 is the insulin responsive glucose transporter. It is expressed in muscle and adipose tissue, and its cell-surface expression can be increased by exercise. The following table summarizes the glucose transporters. Name Distribution Notes GLUT1 Is widely distributed in fetal tissues. In the adult, it is expressed at highest levels in erythrocytes and also in the endothelial cells of barrier tissues such as the blood–brain barrier. However, it is responsible for the low-level of basal glucose uptake required to sustain respiration in all cells. Levels in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels. GLUT2 Is a bidirectional transporter, allowing glucose to flow in 2 directions. Is expressed by renal tubular cells, small intestinal epithelial cells, liver cells and pancreatic beta cells. It is also present in the basolateral membrane of the small intestine epithelium. Bidirectionality is required in liver cells to uptake glucose for glycolysis, and release of glucose during gluconeogenesis. In pancreatic beta cells, free flowing glucose is required so that the intracellular environment of these cells can accurately gauge the serum glucose levels. All three monosaccharides (glucose, galactose and fructose) are transported from the intestinal mucosal cell into the portal circulation by GLUT2 Is a high-capacity and low-affinity isoform. There is some evidence[citation needed] that GLUT 1 and 3 are actually the functional transporters in beta cells. GLUT3 Expressed mostly in neurons (where it is believed to be the main glucose transporter isoform), and in the placenta. Is a high-affinity isoform, allowing it to transport even in times of low glucose concentrations. GLUT4 Found in adipose tissues and striated muscle (skeletal muscle and cardiac muscle). Is the insulin-regulated glucose transporter. Responsible for insulin-regulated glucose storage. Educational objective: GLUT4 is an insulin-responsive glucose transporter found in adipose tissue and muscle that translocates to the cell membrane upon exercise. References: First Aid 2013 page 288 First Aid 2012 page 315 Lund S, Holman GD, Schmitz O, Pedersen O. Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin. Proc Natl Acad Sci USA. 1995;92(13):5817-21. Educational Objective: References: ]]
Approved	Approved::Yes
Keyword	WBRKeyword::Muscle, WBRKeyword::Insulin, WBRKeyword::Glucose, WBRKeyword::Receptor, WBRKeyword::Exercise, WBRKeyword::Transporter
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::