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High Yield Notes
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Content Reviewers:

Rishi Desai, MD, MPH

Insulin is a hormone that’s involved in lowering the blood sugar levels or glycemia after a meal. Insulin comes from the latin insula, which means island, because this hormone is produced by some small islands of cells scattered throughout the pancreas that are called pancreatic islets or islets of Langerhans.

The pancreas lies in the upper left part of the abdomen, right behind the stomach. The vast majority of the pancreas is made up by exocrine glands in charge of secreting digestive enzymes into the small intestine to help digestion. But about 1 to 2% of the mass of the pancreas is made up by the islets of Langerhans, which are endocrine glands made up by five different cell types, and each cell type secretes a specific hormone. The most abundant are the beta cells, which produce insulin. But you can also find alpha cells that secrete glucagon, delta cells that secrete somatostatin, gamma cells that secrete pancreatic polypeptide, and finally epsilon cells that secrete ghrelin.

Let’s focus on beta cells. Beta cells are in charge of producing insulin, which is a peptide hormone encoded by the INS gene on chromosome 11. Insulin is first synthesized as a single polypeptide called preproinsulin. A short tail called leader or signal peptide is cleaved from preproinsulin to form proinsulin. Proinsulin consists of three peptide chains in the order B, C for connecting peptide, and A. Proinsulin is then further cleaved at two positions, releasing a fragment called the C-peptide, and leaving the B- and A- chains, and two disulfide bonds which link the B- and A- chains together to form insulin. This mature insulin is stored inside granules within the beta cells where it waits until it’s released into the blood.

The most important trigger for insulin secretion is glucose. Beta cells are sensitive to glucose concentrations in blood, and when blood glucose levels rise, beta cells secrete insulin into the blood to help lower those levels and store glucose. Other stimulatory factors for insulin secretion include hormones like glucagon and cortisol, which stimulate insulin indirectly by increasing blood glucose levels, increased fatty acid or amino acid concentrations in blood, since insulin is also involved in their storage, and acetylcholine from the parasympathetic nervous system, which helps with digestion, and stimulates insulin secretion to decrease the recently absorbed glucose in blood.

On the other hand, insulin secretion is inhibited by norepinephrine from the sympathetic nervous system, which is activated during stressful situations that demand high energy consumption, and need glucose to be readily available in blood. Other molecules that inhibit insulin production include somatostatin, which is classified as an inhibitory hormone that avoids the excessive release of pancreatic hormones and other hormones like growth hormone.

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