Glucagon is a peptide hormone, produced by alpha cells of the pancreas, that raises the concentration of glucose in the bloodstream. Its effect is opposite that of insulin, which lowers the glucose concentration. Glucagon is a 29-amino acid peptide hormone that is synthesized in pancreatic α cells from the proglucagon precursor by prohormone convertase 2 (PC2). The primary structure of glucagon is identical in most mammals, with the exception of some amino acid differences in guinea pigs and non-mammalian vertebrates.

2. Sequence:
H-His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu-Met-Asn-Thr-OH
Glucagon

3. The role of glucagon in the body
When glucagon is released it can perform the following tasks:
1. Stimulating the liver to break down glycogen to be released into the blood as glucose;
2. Activating gluconeogenesis, the conversion of amino acids into glucose;
3. Breaking down stored fat (triglycerides) into fatty acids for use as fuel by cells

4. Glucose homeostasis, an important physiological function of glucagon, occurs in hepatocytes
through activities that counteract the activities of insulin. In response to low blood sugar,
glucagon is released from the pancreas into the bloodstream. Glucagon binds to the glucagon
receptor (GR) on hepatocytes, leading to an increase in the hepatocellular content of glucose
and the subsequent release of glucose from hepatocytes across the GLUT2 transporter. The
effects of glucagon on hepatic glucose synthesis occur at several levels, including regulatory
short-term effects on enzymes and long-term effects on transcription. Activation of the GR
stimulates signaling pathways involved in glycogenolysis (breakdown of glycogen) and
gluconeogenesis (de novo synthesis of glucose from lactate, pyruvate, glycerol, and some
amino acids). The effects of glucagon to inhibit glycogen synthesis (glycogenesis) and glucose
degradation (glycolysis) are also well established.
Glucose homeostasis

5. Secretion of glucagon is stimulated by:
Hypoglycemia
Epinephrine (via β2, α2, and α1 adrenergic receptors)
Arginine
Alanine (often from muscle-derived pyruvate/glutamate transamination.)
Acetylcholine
Cholecystokinin
Secretion of glucagon is inhibited by:
Somatostatin
Insulin (via GABA)
PPARγ/retinoid X receptor heterodimer.
Increased free fatty acids and keto acids into the blood.
Increased urea production

6. Glucagon receptor (GR) signaling pathways in hepatocytes

7. Proliferative effects of glucagon in other cell types
While glucagon has generally been associated with a reduction of cell
proliferation in hepatocytes, particularly at high concentrations, glucagon
stimulates the proliferation of other cell types. Glucagon stimulates the
proliferation of cultured human colorectal cancer cells, gastrointestinal cells,
and breast cancer cells. As the growth effects of glucagon in these studies
were often observed in the presence of serum, it is possible that a growth
factor in the serum (e.g., EGF) was interacting with glucagon, as has been
reported for the few studies reporting proliferative effects of glucagon/EGF in
hepatocytes at low concentrations of glucagon.

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