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Pancreas
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.
Islets of Langerhans
1 million islets
1-2% of the pancreatic mass Beta () cells produce insulin
Islets of Langerhans
Insulin
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 Structure
1- Large polypeptide 51 AA (MW 6000) 2- Two chains linked by disulfide bonds. A chain : (21 AA) B chain : (30 AA) 3 -Disulfide bonds.
51 amino acids
2 chains linked by disulfide bonds 5800 Dalton molecular weight
Insulin Structure
Insulin Synthesis
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
DNA (chromosome 11) in cells
mRNA
Preproinsulin (signal peptide, A chain, B chain, and peptide C)
proinsulin
insulin
Insulin Synthesis
C- peptide
Essential for Proper folding
Good Indicator of insulin secretion
Insulin Synthesis
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
Then a second phase of gradual increment that lasts as long as blood glucose is high
Figure 6-10
Insulin Signaling
Active transport
Primarily affects liver and muscle
adipose tissue The net result is fuel storage as glycogen , TAG & proteins with inhibition of their mobilization
Liver:
Stimulates glucose oxidation Promotes glucose storage as glycogen Inhibits Glycogenolysis Inhibits gluconeogenesis Muscle: Stimulates glucose uptake (GLUT4) Promotes glucose storage as glycogen
Glucose Transport
GLUT2 (liver, pancreas) GLUT4, insulin sensitive transporter (muscle, adipose tissue) GLUT3 (brain)
Glycogen Synthesis
Short term storage of glucose
Insulin: Summary
Insulin Control
Gastrointestinal hormones
Most Cells
Muscle
Protein synthesis
Glucose uptake Glycogen synthesis
amino
acids
Adipose
Amino acids
Pancreas Insulin
Beta cells
triglycerides
Liver
Blood glucose
Glucose uptake
glucose
Brain
No effect
Feedback
Liver
Uptake of glucose and storage as glycogen
Inhibits glycogen phosphorylase Activates glycogen synthase Inhibits glucose synthesis Promotes excess glucose conversion to fatty acids
Adipose Tissue
Promotes glucose uptake and conversion to glycerol for fat production
Lack of insulin
Free fatty acids build up in blood
Liver metabolizes to produce phospholipids and cholesterol Can lead to excess acetoacetic acid production and buildup of acetone (acidosis, which can lead to blindness and coma)
Glucagon
A 29-amino-acid polypeptide hormone that is a potent hyperglycemic agent
the breakdown of
Gluconeogenesis synthesis of glucose from lactic acid and non-carbohydrates Release of glucose to the blood from liver cells
SYNTHESIS
DNA in cells mRNA Preproglucagon
proglucagon glucagon
Glucagon Signaling
Glycogenolysis
Gluconeogenesis Fatty Acid Oxidation Ketogenesis Uptake of amino acids
DECREASED : Glycogenesis
Regulation of Glucagon Release Increased blood glucose levels inhibit glucagon release.
Amino acids stimulate glucagon release (high protein, low carbohydrate meal). Stress: epinephrine acts on betaadrenergic receptors on alpha cells, increasing glucagon release (increases availability of glucose for energy).
Insulin inhibits glucagon secretion.
GTT
Measurement of the ability of b cells to secrete insulin. Ability of insulin to lower blood glucose.
Normal persons rise in blood [glucose] after drinking solution is reversed to normal in 2 hrs.
Hypoglycemia
Over secretion of insulin. Reactive hypoglycemia:
Caused by an exaggerated response to a rise in blood glucose. Occurs in people who are genetically predisposed to type II diabetes. Insert fig. 19.13
Metabolic Regulation
Anabolic effects of insulin are antagonized by the hormones of the adrenals, thyroid, and anterior pituitary.
Insulin, T3, and GH can act synergistically to stimulate protein synthesis.