Download Insulin

Insulin
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Insulin is a protein hormone produced by the beta cells of the pancreas
Insulin’s function in homeostasis is regulating glucose and fat metabolism. Insulin allows cells in the liver, muscle, and fat tissue transport glucose from the blood. – It causes insertion of glut‐4 transporters into the cell membrane
– Glut‐4 transporters allow facilitated diffusion of glucose from ICF to ECF
◊ In all cells glucose entering the cell is immediately phosphorylated by hexokinase to glucose‐6‐phosphate (G6PO4)
◊ G6PO4 does not fit onto the transporter
◊ Liver alone has an enzyme to reverse the reaction, allowing liver to release glucose to blood if blood glucose is low.
◘ This occurs under the action of the hormone glucagon, which is produced by pancreatic beta cells 1
Insulin
• Insulin promotes glucose oxidation in cell
• Insulin promotes conversion to glycogen in liver and muscle
• Insulin promotes glucose conversion to triglyceride for storage in adipose tissue
– Insulin stops breakdown of tryglyceride to free fatty acid, effectively blocking oxidation of fat for ATP provision
• Insulin promotes uptake of amino acids by cells and their incorporation into protein
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Production and Storage of Insulin
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Conversion of prohormone to insulin occurs in the secretory vesiscle
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GLUT 2
TRANSPORTER
GlycolysisATP
+ATP changes
ATP K+ pump
Change membrane voltage
Open Voltage Regulated
Ca++ channel
Ca++ enters cell and
triggers Ca++ release
Exocytosis of vesicles
containing insulin
Insulin Released into
blood
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Release of insulin – primary control mechanism  negative feedback control of blood glucose level withing “normal” range
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Blood glucose concentration, which increases after eating and nutrient absorbtion from GI tract
1. Glucose enters the β‐cells through the glucose transporter GLUT2
2. Glucose goes into glycolysis and the respiratory cycle, producing ATP
3. Increased intracellular ATP:ADP ratio closes an ATP‐dependent potassium channel
4. The cell membrane potential moves towards “0” from “rest”
hypopolarizes
5. At new membrane potential, voltage‐controlled calcium channels (Ca2+) open
6. Ca2+ flows into the cells
7. Ca2+ entry induces Ca2+ release from storage vescicles
8. ……..Increased amounts of calcium in the cells causes exocytosis of vescicles storing insulin
9. INSULIN ENTERS BLOOD
INSULIN EFFECTS AT TARGET CELL WITH INSULIN RECEPTOR
1. Insulin “released” and enters blood
2. Because it is a protein it is water soluble and travels unbound in the blood
3. Binds with insulin receptors at cell membranes “everywhere”
4. Triggers Tyrosine Kinase (second messenger signal amplification
5. Multiple GLUT 4 TRANSPORTERS placed in cell membrane
6. BLOOD GLUCOSE DECREASES
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Alternate Ways to control insulin release (other than [blood glucose]
Alternate Ways to control insulin release (other than [blood glucose]
Amino acid
Digestive
hormone
Normal Primary Regulation
Other modulators
Primary
glucoregulatory
hormonehormone- glucagon
Secondary
hormones
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CHEMICAL CATEGORIES OF HORMONES
• PEPTIDES /PROTEINS
– Insulin
• LIPIDS/STEROIDS
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Cortisol is a specific Glucoregulatory hormone and a “Stress hormone
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Steroid Hormones bind to intracellular recepors and trigger protein synthesis
• Aldosterone is a mineral corticoid – A steroid that causes manufacture and insertion of Na+/K+ transporters in the walls of kidney cells
◊ Secrete K+ to collecting duct for excretion
◊ Return Na+ to plasma for retention
◘ Set up an osmotic gradient for Water to be retained
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