The Pancreas And Energy Metabolism Notes

The Pancreas and Energy Metabolism

The pancreas is a combined exocrine and endocrine gland. The exocrine part of the pancreas secretes digestive enzymes in response to gastrointestinal hormones such as CCK. It also produces bicarbonate to neutralise stomach acid in response to secretin.

The endocrine cells form clusters called the islets of Langerhans which are scattered throughout the gland. Four peptide hormones are secreted by these cells – insulin from beta cells, glucagon from alpha cells, somatostatin from delta cell sand pancreatic polypeptide from PP cells. Most of the cells in the islets of Langerhans are insulin producing beta cells.

The capillaries in the pancreas transport the secreted hormones to the portal vein, which conducts blood from the digestive tract to the liver. Glucagon exerts its effects primarily on the cells of the liver, whilst insulin affects many cells throughout the body.

1. Insulin

Insulin secretion is enhanced after meals in response to an increase in glucose and amino acids in the blood.

Like other peptide hormones, insulin is first produced as a pro-hormone. Pro-insulin is converted to insulin immediately before secretion by removal of an inactive peptide called C-peptide. Active insulin consists of two polypeptide chains of different lengths connected by two disulphide bridges. Insulin is metabolised in the liver and kidneys by cleavage of the disulphide bonds and shortening of the polypeptide chains.

When glucose enters the beta cells of the islets of Langerhans via GLUT-2 transporters it is phosphorylated by glucokinase. This traps the glucose in the cell. There is an increase in ATP production which inhibits potassium-sensitive potassium channels. Increased intracellular potassium leads to depolarisation, which activates voltage-gated calcium channels. The influx of calcium triggers exocytosis of insulin.

Glucose stimulation of insulin secretion is biphasic. Following an increase in plasma glucose, the release of preformed insulin causes an initial and immediate increase in secretion. This phase is followed by a more prolonged secretion of newly synthesised insulin.

Gastric inhibitory peptide (GIP) and other gastrointestinal hormones also stimulate the release of insulin. These hormones are released when food enters the small intestine. This anticipatory release of insulin is why insulin response is greater to orally administered glucose than to intravenously administered glucose.

Sympathetic activity inhibits insulin secretion, whilst parasympathetic activity stimulates it.

Insulin binds to membrane receptors composed for four parts. Two alpha subunits are located entirely out of the cell membrane and contain the insulin binding domain. Tow beta subunits span the cell membrane and act as a local tyrosine kinase when activated. The activated insulin receptor causes phosphorylation of multiple intracellular enzymes, which activates some enzymes and inhibits others.

The metabolic actions of...

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