Glucose-mediated insulin release is mediated through
A. ATP-dependent K channels
B. CAMP
C. Carrier modulators
D. Receptor phosphorylation
A. ATP-dependent K channels
B. CAMP
C. Carrier modulators
D. Receptor phosphorylation
. Ans A
•
Metabolism of glucose by the pancreatic beta cell triggers insulin secretion;
The pancreatic beta-cells take up and metabolize glucose, galactose, and
mannose, and each can provoke insulin secretion by the islet; Some amino acids
especially arginine and leucine can also weakly stimulate insulin secretion;
• Glucose enters the 13-cell via the GLUT2 transporter; In the presence of glucokinase, it undergoes glycolysis; Intracellular ATP is increased; Due to this ATP, the ATP-sensitive K channel in the 13-cell membrane closes;
• K+ accumulates within the cell, causing depolarization of the membrane; This activates voltage-gated Ca2+ channel in the membrane; Ca2 influx occurs; it leads to activation of Ca2+_calmodulin phosphorylation cascade; This will eventually lead to insulin release; Thus, option a is correct since the question is about glucose-mediated insulin release;
• Glucagon stimulates insulin release by increasing cAMP levels in beta-cells; Somatostatin inhibits insulin release by decreasing cAMP;
• Receptor phosphorylation: This is elicited by the insulin receptor in the target tissues; Insulin receptor has two cr and two 13 subunits; The 13 subunit spans the membrane and has tyrosine kinase activity; When insulin binds to 13 subunit, tyrosine kinase autophosphorylates the beta subunits; The phosphorylated receptor then phosphorylates intracellular proteins, to produce the insulin effects in the target tissues; Compare this with hormones that activate second messenger such as cAMP; The second messenger activates protein kinases which then cause phosphorylation of selected proteins;
• Receptors that themselves are catalytic:
o Receptor tyrosine kinase: Receptor itself has intrinsic tyrosine kinase activity; It phosphorylates tyrosine residues on itself and other proteins, e;g;, insulin and IGFs; Compare this with other ligands that activate second messenger such as cAMP; They phosphorylate serine and/or threonine residues of cellular proteins;
o Tyrosine kinase associated receptor: Receptor itself does not have intrinsic tyrosine kinase activity; It activates proteins that have tyrosine kinase activity, e;g;, GH receptor;
• Glucose enters the 13-cell via the GLUT2 transporter; In the presence of glucokinase, it undergoes glycolysis; Intracellular ATP is increased; Due to this ATP, the ATP-sensitive K channel in the 13-cell membrane closes;
• K+ accumulates within the cell, causing depolarization of the membrane; This activates voltage-gated Ca2+ channel in the membrane; Ca2 influx occurs; it leads to activation of Ca2+_calmodulin phosphorylation cascade; This will eventually lead to insulin release; Thus, option a is correct since the question is about glucose-mediated insulin release;
• Glucagon stimulates insulin release by increasing cAMP levels in beta-cells; Somatostatin inhibits insulin release by decreasing cAMP;
• Receptor phosphorylation: This is elicited by the insulin receptor in the target tissues; Insulin receptor has two cr and two 13 subunits; The 13 subunit spans the membrane and has tyrosine kinase activity; When insulin binds to 13 subunit, tyrosine kinase autophosphorylates the beta subunits; The phosphorylated receptor then phosphorylates intracellular proteins, to produce the insulin effects in the target tissues; Compare this with hormones that activate second messenger such as cAMP; The second messenger activates protein kinases which then cause phosphorylation of selected proteins;
• Receptors that themselves are catalytic:
o Receptor tyrosine kinase: Receptor itself has intrinsic tyrosine kinase activity; It phosphorylates tyrosine residues on itself and other proteins, e;g;, insulin and IGFs; Compare this with other ligands that activate second messenger such as cAMP; They phosphorylate serine and/or threonine residues of cellular proteins;
o Tyrosine kinase associated receptor: Receptor itself does not have intrinsic tyrosine kinase activity; It activates proteins that have tyrosine kinase activity, e;g;, GH receptor;
