Insulin and Glucagon Kamilah Gonzalez

What is Insulin? · Hormone made by the Beta cells of our pancreas that regulates blood sugar levels, preventing Hyperglycemia (Too High) ·After a meal, your blood sugar levels rise, stimulating the release of insulin, which enables cells in the liver, muscles, and fat tissues to absorb glucose, either storing it as glycogen or use it as fuel source ·With excess glucose present, higher amounts of insulin are released to maintain homeostasis ·Deficiency in insulin - Diabetes Mellitus Without insulin, the body cannot process glucose effectively and glucose begins to build up in the bloodstream instead of being transported to different cells (urinated out, hence diabetes mellitus Synthetic insulin is used as a drug to treat diabetes.

Structure of Insulin ·Consists of 2 polypeptide chains: Chain A and Chain B with a TOTAL of 51 Amino Acids →Chain A contains 21 Amino Acids →Chain B contains 30 Amino Acids ·The 2 chains are linked together by Disulfide Bonds Chain A has an internal disulfide bridge, meanwhile Chain B forms 2 disulfide bridges

→Insulin mRNA is translated as a single chain precursor - preproinsulin →It’s insertion into the endoplasmic reticulum causes the removal of the signal peptide forming proinsulin (has 3 polypeptide chains: C chain connecting with both A and B chain) →Within the ER, the C chain is snipped by endopeptidase forming insulin and a free C- peptide which is now packaged in the Golgi bodies →When the pancreas is stimulated, insulin is secreted by the Beta cells via exocytosis Synthesis of Insulin

Insulin Transduction Pathway CHO is ingested, digested, and absorbed, causing rise in blood glucose concentration → release of insulin Glucose passively diffuses into Beta cell of pancreas via GLUT2 Within the Beta cells: Glucose → Glucose-6-Phosphate (G6P) through Glucokinase G6P oxidized to form ATP, which inhibits the ATP sensitive Potassium ion channels causing Potassium ion channel to close. This closing of channel causes depolarization of cell membrane causing it to stretch triggering the VD-Calcium channel to open, resulting in influx of Calcium ions Influx of Calcium ions stimulates the fusion of insulin vesicles to the membrane (insulin binding to insulin receptor) → secretion of insulin The pathway is influenced by fed vs. fasting states, stress levels, and other hormones

What is Glucagon? ·It’s effect is opposite to that of insulin ·Hormone made by the Alpha cells of our pancreas, when there is a deficit of glucose available to the body, preventing Hypoglycemia (Too Low) ·The release of Glucagon causes the liver to convert stored glycogen into usable glucose (Glycogenolysis) and activating Gluconeogenesis ·Synthesis of Glucagon is similar to Insulin, except when blood sugar drops, insulin production drops and more glucagon is produced Glucagon generally elevates the concentration of glucose in the blood by promoting gluconeogenesis and glycogenolysis

Structure of Glucagon 29 Amino Acid Polypeptide

Glucagon Pathway →Once released, glucagon binds to the plasma membrane’s Glucagon receptor, G protein- coupled receptor →Binding causes a conformational change in the receptor activating the G proteins (w/ subunits: Alpha, Beta,and Gamma), causing change from GDP → GTP, releasing the Alpha subunit of G protein →Alpha subunit activates adenylate cyclase, converting ATP → cAMP which activates protein kinase A (PKA) - regulates the rxn catalyzing fructose-2,6-bisphosphate by slowing the rate of its formation, thereby inhibiting the flux of glycolysis pathway and allowing gluconeogenesis to prevail *PKA also activates phosphorylase kinase - converts Glycogen Phosphorylase B into Phosphorylase A, resulting in the release of Glucose-1-Phosphate

Glucagon Pathway

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