glucagon and glucagon-like peptide 1

Glucagon
180アミノ酸よりなる前駆体がPCSK1、またはPCSK2（神経内分泌変換酵素）により切断され、グルカゴン（53-81、26ペプチド）やglucagon-like peptide 1(GLP-1)（92 – 128アミノ酸、37ペプチドの前駆体）などを生じる。
Cleaved into the following 8 chains:

  1. Glicentin
  2. Glicentin-related polypeptide
    • Short name=GRPP
  3. Oxyntomodulin
    • Short name=OXM
    • Short name=OXY
  4. Glucagon
  5. Glucagon-like peptide 1
    • Short name=GLP-1
    • Alternative name(s):
    • Incretin hormone
  6. Glucagon-like peptide 1(7-37)
    • Short name=GLP-1(7-37)
  7. Glucagon-like peptide 1(7-36)
    • Short name=GLP-1(7-36)
  8. Glucagon-like peptide 2
    • Short name=GLP-2

Function

Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes. Ref.9 Ref.10 Ref.11
GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis. Ref.9 Ref.10 Ref.11
GLP-1は重要なグルコース依存性インスリン分泌刺激作用をもつ。腸管の運動による血漿グルカゴンレベルの抑制に重要な役割をもつ。インスリン作用とは別に満腹感を抑制し、末梢組織でグルコースを処理する。小腸上皮に成長を促す作用をもつ。視床下部下垂体系に働き、LH,TSH,CRH,オキシトシン、バソプレシンの分泌を調節する。膵臓ランゲルハンス島B細胞の増殖作用がある。アポトーシスも抑制する。
GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability.
GLP-2は腸の成長を刺激し、小腸の絨毛の高さを増加させると同時に陰窩の細胞の増殖と腸管細胞のアポトーシスを減少させる。胃から大腸までの消化管はGLP-2作用の標的である。栄養の恒常性において鍵となり、栄養の吸収を促進する。
Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness. Ref.9 Ref.10 Ref.11
Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life. Ref.9 Ref.10 Ref.11

Subcellular location

Secreted.

Tissue specificity

Glucagon is secreted in the A cells of the islets of Langerhans. GLP-1, GLP-2, oxyntomodulin and glicentin are secreted from enteroendocrine cells throughout the gastrointestinal tract. GLP-1 and GLP-2 are also secreted in selected neurons in the brain.
グルカゴンは膵臓ランゲルハンス島A細胞から、GLP-1は消化管分泌細胞から、又は大脳の神経細胞でも分泌される。

Induction

Glucagon release is stimulated by hypoglycemia and inhibited by hyperglycemia, insulin, and somatostatin. GLP-1 and GLP-2 are induced in response to nutrient ingestion.
グルカゴンは低血糖刺激、高血糖の阻害、インスリン、ソマトスタチンにより分泌刺激を受ける。GLP-1は栄養素の消化が刺激となる。

Post-translational modification

Proglucagon is post-translationally processed in a tissue-specific manner in pancreatic A cells and intestinal L cells. In pancreatic A cells, the major bioactive hormone is glucagon cleaved by PCSK2/PC2. In the intestinal L cells PCSK1/PC1 liberates GLP-1, GLP-2, glicentin and oxyntomodulin. GLP-1 is further N-terminally truncated by post-translational processing in the intestinal L cells resulting in GLP-1(7-37) GLP-1-(7-36)amide. The C-terminal amidation is neither important for the metabolism of GLP-1 nor for its effects on the endocrine pancreas. Ref.12 Ref.13
グルカゴン前駆体は翻訳後修飾により、A細胞、または小腸L細胞のそれぞれで別のプロセッシングを受ける。A細胞では、グルカゴンがPCSK2/PC2により切り出される。小腸L細胞ではPCSK1/PC1がGLP-1,GLP-2等を遊離する。GLP-1はさらにL細胞でN末端を切り離される。C末端はアミド化される。

Pharmaceutical use

Available under the names Glucagon (Eli Lilly) and GlucaGen or Glucagon Novo Nordisk (Novo Nordisk). Used to treat severe hypoglycemia in insulin-dependent diabetics.

Miscellaneous

In the glucagon antagonist, His-53 and Phe-58 are missing. This antagonist has been successfully utilized to reduce glucose concentration in vivo.

Sequence similarities

Belongs to the glucagon family.