Topic 05-Insulin and Glucagon-S_2011

Topic 05-Insulin and Glucagon-S_2011 - PGY452/552 Human...

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PGY452/552: Human Physiology: Endocrinology A. Click to edit Master subtitle style 5. Short term metabolic control by insulin & glucagon Insulin--anabolism 1) Regulation of secretion 2) Signaling mechanism 1) Anabolic effects B. Glucagon--catabolism C. Glucose homeostasis
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Insulin & glucagon are synthesized in the endocrine pancreas Pancrea s Small intesti ne Location allows pancreatic hormones to be in higher concentration near major site of action: Liver 2 2
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Insulin & glucagon are secreted from specialized cells Exocrine cells (digestive enzymes) α cells° glucagon β cells * insulin & amylin δ cells Islet of Langerhan s Blood flow Blood flow from β cells (center) to α cells means that insulin can regulate glucagon secretion 3 3
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Insulin is the primary anabolic Short-term: Regulates storage & uptake of glucose Long-term: Fat storage Growth & development Regulation of release Glucose Other important factors We’ll get to this in the next topic T K TK 4 4
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Insulin synthesis: typical for a peptide hormone Synthesized from a higher MW precursor Cleaved in trans- golgi to form 3 peptides Insulin A & B chains Disulfide linked MW 6000; 51 aa C-peptide Activity? Marker for secretion S S S S S S + C peptide Mature Insulin in secretory vesicle A B A B C p 5 3 mR NA E R N C C S S S S S S S H H S H S H S C peptide Ins ulin A B S H S H N proinsu lin Riboso me E R N C S S S S S S Cleav age trans - golgi 5 5
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Insulin secretion is the central point Dynamic & highly regulated Released in response to Extracellular [glucose] Intracellular [ATP] Other release factors Enteric hormones Stress hormones Anything that ° intracellular [ATP] 6 6
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physiological range of [glucose] Hexokinase (muscle, adipose) Glucokina se (β cells, liver) 0 1 0 5 1 5 10 0 % activi ty plasma [glucose] in mM P A T P A D P gluc ose glucose-6- phosphate glycol ysis Molecular mechanism of release-- Step 1: glucokinase Glucokinase and hexokinase
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