Pancreas Figs(8 pages)
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- Lecture number:
- Lecture Note
- University of Southern California
- Bisc 307l - General Physiology
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BISC 307L 2nd Edition Lecture 16 Current Lecture Control of Insulin Secretion in Pancreatic Beta Cells Insulin has special significance because it was the first well studied endocrine hormone – structure was understood, gene identified, and it was successfully synthesized through recombinant DNA technology. The impetus for this was the therapeutic value of insulin in combatting diabetes. The rectangle is a beta cell, and at the bottom is insulin being released into the blood through exocytosis. How does a cell know when it is time to secrete insulin? Primary control, shown in the center of the figure, is exerted by glucose itself and by amino acids in the plasma, which are high intracellularly during the absorptive state when these nutrients are being absorbed. Glucose enters the beta cell by glut2 facilitated diffusion transporter in upper right corner. It stimulates energy metabolism inside the cell, which increases intracellular ATP - ATP binds to the inside of the ATP sensitive K channel on the right, in the membrane, which is normally open at low levels of ATP (when glucose is low in the blood). When blood glucose and intracellular ATP both rise, the formerly open channel is blocked and no longer hyperpolarizes the cell. Blocking of this channel therefore depolarizes the cell, causing vg Ca channels near the release sites to open. Free Ca entering the beta cell triggers exocytosis of insulin carrying vesicles. This is the main mechanism of control. On the bottom left – things that modulate/modify this primary level of control. The main mechanism to inhibit glucose dependent insulin secretion is sympathetic nerve activity. And the two mechanisms that stimulate insulin release: 1. parasympathetic activity 2. the secretion of hormones that are collectively called incretins – they are small intestine hormones that stimulates glucose dependent insulin secretion from beta cells. The two main ones are GLP1 (glucagon-like peptide) and GIP(was called gastric inhibitory peptide, but now it stands for glucose-dependent insulinotropic peptide). How do they work? Both of these incretins are part of a feed forward mechanism that anticipates a rise in nutrients in the blood before it occurs. So GLP and GIP are released by the small intestine at the beginning of the meal or in anticipation of a meal, to prime the beta cells so they are more sensitive to the rises in glucose and amino acids that result when start eating. This way, they minimize the surge in blood glucose that would otherwise occur if this feed forward mechanism was not operative. Insulin Stimulates Glucose Uptake in Resting Skeletal Muscle and adipocytes The action of insulin on cells – it affects most cells in the body, but we will be focusing on three types: cells of the skeletal muscle, adipose tissue/fat, and liver. This diagram focuses on insulin’s effect on glucose transporters in the membrane of resting skeletal muscles and adipose fat cells. Purple = plasma membrane of cell. Above = glucose molecules. Insulin binds to the tyrosine kinase insulin receptor and stimulates insertion of freeform ...
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