Master Insulin Synthesis with Picmonic for Medicine

Preproinsulin is a proinsulin molecule with a signal peptide attached to its N-terminus. It is a biologically inactive precursor of insulin.

Removal of the signal peptide from preproinsulin results in the formation of proinsulin in the rough endoplasmic reticulum of pancreatic beta cells.

Removal of the signal peptide from N-terminus of preproinsulin results in the formation of proinsulin.

Processing of proinsulin in the Golgi apparatus results in the formation of biologically active insulin. This processing involves the removal of the C-peptide and connection of the A- and B-chains through disulfide bonds.

Synthesis, storage, and release of insulin mainly take place in beta cells of the pancreas. Pancreatic beta cells are located in the islets of Langerhans. They make up the majority of the cells in the islets.

C-peptide is a short polypeptide that connects insulin's A-chain to its B-chain in the proinsulin molecule. C-peptide is released with insulin after the cleavage of proinsulin. Hence, C-peptide is a byproduct of endogenous insulin synthesis. This is important clinically as increased C-peptide levels reflect an increased endogenous production of insulin (e.g., insulinoma, sulfonylurea use). In contrast, exogenous insulin administration (e.g., a patient who overdosed on injected insulin) won't result in the elevation of C-peptide levels as exogenous insulin lacks C-peptide.

An insulinoma is a tumor of the pancreas that is derived from the beta cells of the pancreas. This tumor secretes excessive amounts of insulin and can result in hypoglycemia. As the insulin is synthesized endogenously, C-peptide levels will be elevated.

Sulfonylureas (e.g. glyburide, glipizide) are medications used to treat diabetes mellitus. These drugs help to increase endogenous pancreatic secretion of insulin so insulin and C-peptide levels in a patient taking sulfonylureas should be high-normal or elevated.

Surreptitious insulin use is characterized by high insulin levels and low C-peptide levels. Exogenous insulin doesn't contain C-peptide, and its ingestion results in increased total insulin levels, which suppresses the production of endogenous insulin due to feedback inhibition, hence C-peptide levels will be low.