Glucagon

GLUCAGON

Peptide hormone secreted pancreatic alpha cells
Counterregulatory hormone: opposes insulin action
Other counterregulatory hormones: epinephrine, norepinephrine, cortisol, growth hormone
Binds G-protein coupled receptors in specific tissues (i.e. liver)
Short half-life

PANCREAS

Islets of Langerhans (1-2% of pancreatic beta cells)

Beta cell: secretes insulin
Alpha cell: secretes glucagon (opposes insulin)

GLUCAGON SECRETION

Pancreatic alpha cell

Glucagon: single polypeptide chain
Preproglucagon: cleaved to produce diff. products in diff. tissues (i.e. intestinal GLP-1)
Preproglucagon --> --> --> glucagon

Activate secretion:

Low blood glucose (primary stimulus)
Stress hormones: (nor)epinephrine override alpha cell's response during physiologic stress
Amino acids: high protein meal stimulates glucagon secretion (counters insulin secretion)

INSULIN VS. GLUCAGON

Glucose levels maintained in tight range
Healthy adult fasting blood glucose: < 100 mg/dL

GLUCAGON MECHANISM OF ACTION

Hepatocytes: receptors for glucagon and epinephrine

Counterregulatory hormones control same processes, but respond to other stimuli (i.e. stress)
Muscle cells: only receptors for epinephrine NOT glucagon

1. Binds G-protein coupled receptor on hepatic cell 2. Alpha subunit exchanges GDP for GTP 3. Alpha subunit activates adenylyl cylase, which activates PKA 4. PKA phosphorylates downstream enzymes 5. Activates glycogen & lipid breakdown, and gluconeogenesis 6. Inhibits glycogen, protein and lipid synthesis

Long-term response: increases transcription of gluconeogenic enzymes (~hours/days)

CLINICAL CORRELATION

Hypoglycemia

Acute drop in blood glucose levels to below 60 mg/dL
Symptoms range from dizziness to coma and even death
Brain and red blood cells depend on glucose for energy

Glucagon

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