GI Secretions — Pancreatic Secretions

Pancreatic Secretions

Pancreas: Exocrine Secretions

Contents

• Digestive Enzymes:
  • Proteases: trypsin and chymotrypsin: proteolysis
  • Pancreatic Lipase: Hydrolysis of triglycerides
  • Amylase: Hydrolysis of carbohydrates
  • Other Pancreatic Enzymes: Ribonuclease, deoxyribonuclease, gelatinase and elastase
• Bicarbonate and water:
  • Bicarbonate neutralizes acid coming into small intestine from stomach
  • Produced by carbonic anhydrase → secreted into the lumen of the duct → pancreatic juice

Control of pancreatic exocrine secretions

• Vagus nerve:
  • Low level stimulus via Ach in response to anticipation of meal
• Enteric endocrine system:
  • Cholecystokinin:
    • secreted in duodenum
      • Stimulated by partially digested proteins and fats
    • CCK released into blood → binds to pancr acinar cells
  • Secretin:
    • Secreted in proximal small intestine
      • In response to acid in duodenum
    • Stimulates duct cells to secrete water and bicarb
  • Gastrin:
    • Secreted by stomach
      • in response to gastric distension and irritation
    • Stimulates acinar cells to secrete digestive enzymes

Occurs in three phases: cephalic → Gastric → Intestinal

Pancreas: Endocrine Secretions

Insulin

• Peptide hormone produced in beta cells of Islets of Langerhans in pancreas
• Proinsulin: insulin precursor; A + B chain joined by 2 disulphide bridges + C peptide
• Insulin: formed when C peptide is cleaved by endopeptidases → insulin + free C peptide are packaged in vesicles
• Exocytosis:
  • Primary trigger = ↑BSL
    o ↑BSL → ↑facilitated diffusion of glucose through GLUT2 transmembrane channels into B-islet cells → ↑metabolic activity of cell → ↑formation of ATP
  • ATP-gated K channels on beta islet cell membrane are closed by ↑ATP levels → ↓ K flux → membrane depolarisation → triggers opening of voltage gated Ca2+ channels → Ca2+ influx triggers insulin containing vesicle exocytosis
• Plasma insulin secretion occurs in 2 phases
  • ↑BSL → rapid ↑insulin concentration as vesicles with pre-formed insulin empty contents
  • When all vesicles have emptied → B islet cells release insulin as it is synthesised
• Physiological effects:
  • Facilitation of glucose uptake: GLUT4 in adipose tissue, skeletal muscle, heart – require insulin to facilitate cellular glucose uptake. NB brain has GLUT-1 and liver has GLUT-2 which are not insulin dependent
  • Storage of metabolic substrates: hepatic glycogenesis, FA synthesis in liver, ↑esterification of FAs (to make TGs) in adipose tissue
  • Inhibition of endogenous glucose production: insulin inhibits lipolysis + glycogenolysis + gluconeogenesis
  • Cellular uptake of amino acids and K
    • ↑amino acid uptake → promotes protein synthesis
    • ↑K uptake: prevents hyperkalaemia following meal

Glucagon

• peptide hormone produced by alpha cells of islets of Langerhans
• unlike insulin, the have no glucose sensing apparatus
• Secretion:
  • stimulated by hypoglycaemia: hypoglycaemia-induced ↑ANS activity (i.e. indirect) + ↑adrenaline
  • inhibited by: insulin, somatostatin, ↑freeFA and ketone body concentrations
• Actions: ↑plasma glucose conc by: promoting gluconeogenesis+glycogenolysis, inhibits glycolysis in liver. Important during starvation

Somatostatin

• secreted by delta cells in pancreatic islets (and pyloric antrum, duodenum)
• inhibitory hormone
• Stimuli for release: (i) ↑ plasma levels of glucose, a.a. and FA, and (ii) Acidic gastric environment
• inhibited by vagus nerve
• Effects:
  • ↓ secretion of pancreatic hormones (insulin, glucagon, pancreatic polypeptide)
  • ↓ GH release from pituitary
  • ↓ gastric, duodenal and GB motility
  • ↓ secretion and absorption in GIT (Eg. gastric acid secretion)

Pancreatic polypeptide

• Polypeptide secreted by F-cells of Islets of Langerhans
• influence GIT function (Ie. ↑enzyme secretion, ↓ intestinal motility, Etc.)