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Insulin and Glucagon (Blood glucose levels (Pancreas (Endocrine (Islets of…
Insulin and Glucagon
Blood glucose levels
70-110 mg/dL or 3.9-6.1 mmol/L
Hypoglycemia (below)
Hyperglycemia (above)
Disease
Type II diabetes
Type I diabetes
Pancreas
Endocrine
Islets of Langerhans
Function (metabolic actions)
Energy metabolism
Glucagon: fast
FA and ketone bodies
Insulin: fed
Glucose
(Glucose) Homeostasis
Insulin-independent
Brain, RBC, liver
Increased AMPK/AMP produce ATP
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beta oxidation
Glycolysis
Glucose uptake
Insulin-dependent GLUT-4
Muscle/adipose tissue
High I/G
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Low I/G
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Cell types
beta: most abundant; inside
Insulin
delta
Somatostatin
PP
Pancreatic polypeptide
alpha
Glucagon
Exocrine
Ductal cells
Biosynthesis
Insulin
Preproinsulin
Proinsulin
Stored in vesicles
Insulin
#
C-peptide
#
Signal causes equimolar amounts released
Dimers
Zn2+-hexamers
insulin crystals
RER to cis-Golgi
Signal sequence
Nucleus to cytoplasm to RER lumen
Protein disulfide isomerase and chaperone
Glucagon
Proglucagon
Small intestine
GLP-1
#
Pancreatic alpha cells
Glucagon
Secretion
Regulated
Secretagogues
GLUT-2
Glucose phosphorylated
ATP levels increase
ATP-sensitive K+ channel inhibited
Membrane depolarization
Voltage-gated Ca2+ channel opens
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Sulfonylurea inhibits
Constitutive
Regulation
Insulin
Major
Blood glucose +
Minor
Incretins +
Epinephrine -
Neural input (CNS) +/-
Dietary amino acids +
Glucagon
Major
Blood glucose -
Minor
Epinephrine +
Neural input +
Cortisol, growth hormones
Insulin, incretins -
Dietary amino acids +
Signal transduction mechanisms
Insulin
RTK
liver, muscle, adipose tissue
Glucagon
GPCR
Liver