Endocrine Physiology The Endocrine Pancreas. A triangular gland, which has both exocrine and...
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Transcript of Endocrine Physiology The Endocrine Pancreas. A triangular gland, which has both exocrine and...
![Page 1: Endocrine Physiology The Endocrine Pancreas. A triangular gland, which has both exocrine and endocrine cells, located behind the stomach Strategic location.](https://reader035.fdocuments.us/reader035/viewer/2022062304/56649f1d5503460f94c33b65/html5/thumbnails/1.jpg)
Endocrine Physiology
The Endocrine Pancreas
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• A triangular gland, which has both exocrine and endocrine cells, located behind the stomach
• Strategic location
• Acinar cells produce an enzyme-rich juice used for digestion (exocrine product)
• Pancreatic islets (islets of Langerhans) produce hormones involved in regulating fuel storage and use.
Pancreas
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The Endocrine Pancreas
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Islets of Langerhans
• 1 million islets
• 1-2% of the pancreatic mass
• Beta (β) cells produce insulin
• Alpha (α) cells produce glucagon
• Delta (δ) cells produce somatostatin
• F cells produce pancreatic polypeptide
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Islets of Langerhans
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• Hormone of nutrient abundance
• A protein hormone consisting of two amino acid chains linked by disulfide bonds
• Synthesized as part of proinsulin (86 AA) and then excised by enzymes, releasing functional insulin (51 AA) and C peptide (29 AA).
Insulin
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1- Large polypeptide 51 AA (MW 6000)
2- Tow chains linked by disulfide bonds.
A chain (21 AA)
B chain (30 AA)
3 disulfide bonds.
Insulin Structure
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Insulin Structure
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Protein and Polypeptide Synthesis and Release
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• insulin gene encodes a large precursor of insulin (preproinsulin)
• During translation, the signal peptide is cleaved (proinsulin)
• During packaging in granules by Golgi, proinsulin is cleaved into insulin and C peptide
Insulin Synthesis
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DNA (chromosome 11) in β cells
mRNA
Preproinsulin (signal peptide, A chain,
B chain, and peptide C)
proinsulin
insulin
Insulin Synthesis
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Insulin Synthesis
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• Insulin synthesis is stimulated by glucose or feeding and decreased by fasting
• Threshold of glucose-stimulated insulin secretion is 100 mg/dl.
• Glucose rapidly increase the translation of the insulin mRNA and slowly increases transcription of the insulin gene
Insulin Synthesis
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Glucose is the primary stimulator of insulin secretion
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Regulation of Insulin Secretion
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• No insulin is produced when plasma glucose below 50 mg/dl
• Half-maximal insulin response occurs at 150 mg/dl
• A maximum insulin response occurs at 300 mg/dl
• Insulin secretion is biphasic:
• Upon glucose stimulation– an initial burst of secretion (5-15 min.)
• Then a second phase of gradual increment that lasts as long as blood glucose is high
Regulation of Insulin Secretion
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Insulin secretion is biphasic
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Insulin Signaling
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Insulin Signaling
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Insulin Action on Cells:
• Insulin is the hormone of abundance.
• The major targets for insulin are:
• liver
• Skeletal muscle
• adipose tissue • The net result is fuel storage
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Insulin Action on Carbohydrate Metabolism:
Liver:• Stimulates glucose oxidation
• Promotes glucose storage as glycogen
• Inhibits glycogenolysis
• Inhibits gluconeogenesis
Muscle:• Stimulates glucose uptake (GLUT4)
• Promotes glucose storage as glycogen
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Insulin Action on Carbohydrate Metabolism :
Adipose Tissue: • Stimulates glucose transport into
adipocytes
• Promotes the conversion of glucose into triglycerides and fatty acids
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Glucose Transport
• GLUT2 (liver, pancreas)
• GLUT4, insulin sensitive transporter (muscle, adipose tissue)
• GLUT3 (brain)
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Glycogen Synthesis
• Short term storage of glucose
• Activates glycogen synthase
• Inhibit glycogen phosphorylase
• Glycolysis is also stimulated by insulin
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Lipogenic and antilipolytic
• Insulin promotes lipogenesis and inhibits lipolysis
• Promotes formation of α-glycerol phosphate and fatty acid synthesis
• Stimulates fatty acid synthase (FAS)
• Inhibits hormone sensitive lipase (HSL)
• Activates lipoprotein lipase (LPL)
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Protein Synthesis and Degradation
• Insulin promotes protein accumulation:
1. Stimulates amino acid uptake
2. Increases the activity of protein synthesis
3. Inhibits protein degradation
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Action of insulin on Liver:
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Action of insulin on Fat:
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Action of insulin on Muscle:
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Insulin action (summary):
• glucose uptake in most cells
• glucose use & storage
• protein synthesis
• fat synthesis
Dominates in Fed State Metabolism
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Insulin: Summary
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• A 29-amino-acid polypeptide hormone that is a potent hyperglycemic agent
• Produced by α cells in the pancreas
• Its major target is the liver, where it promotes:
• Glycogenolysis – the breakdown of glycogen to glucose
• Gluconeogenesis – synthesis of glucose from lactic acid and noncarbohydrates
• Release of glucose to the blood from liver cells
Glucagon
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Glucagon Signaling
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SYNTHESIS
DNA in α cells
mRNA
Preproglucagon
proglucagon
glucagon
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Factors Affecting Glucagon Secretion:
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Glucagon Action on Cells:
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Insulin & Glucagon Regulate Metabolism
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The Regulation of Blood Glucose Concentrations
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• A serious disorder of carbohydrate metabolism
• Results from hyposecretion or hypoactivity of insulin
• The three cardinal signs of DM are:
• Polyuria – huge urine output
• Polydipsia – excessive thirst
• Polyphagia – excessive hunger and food consumption
Diabetes Mellitus (DM)
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Diabetes Mellitus Type I
• Type 1: beta cells destroyed- no insulin producedchronic fasted state, "melting flesh", ketosis, acidosis, glucosurea, diuresis & coma
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• Over 15 million diabetics in USA- 10% type I, 90% type II
• More common is some ethnic groups
• Insulin resistance keeps blood glucose too high
• Chronic complications: atherosclerosis, renal failure& blindness
Diabetes Mellitus: Type II a Group of Diseases
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Diabetes Mellitus: Type II a Group of Diseases
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GTT
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Symptoms of Diabetes Mellitus
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Diabetes Mellitus (DM)