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Insulin Synthesis and Secretion | Part 2/4

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▬▬▬▬▬▬▬▬▬▬ Contents of this video ▬▬▬▬▬▬▬▬▬▬

00:00:00 GLUT2 Transporters
00:07:15 Molecular/Cellular mechanisms which leads for the release of insulin on high blood glucose level
00:25:58 Review until now
00:29:15 Type 2 Diabetes Mellitus in younger age due to mutant Glucokinase function
00:33:15 Action of drugs which work as ATPsensitive K+ channel blockers
00:39:13 Action of drug which work as ATPsensitive K+ channel activator and inhibits the secretion of insulin
00:42:16 Action of Diazoxide in Insulinoma patients



Outline: Synthesis, Storage, Release & Regulation of Insulin.
Exocrine & Endocrine function. Acinar cells; synthesize digestive enzymes and release into the duodenum.

The endocrine function of cells: Islets of Langerhans; scattered within the pancreas comprise 1% of the pancreas, millions in number.
Cells, B cells, D cells, F cells/PP cells in a single Islet.
B cells in the center of Islets, surrounded by A cell’s outer parts.
D cells; are scattered around the Islet.

Products produced by different cells.
B cells = Insulin; stimulated by glucose intake.
Cpeptide released in equimolar quantity with insulin.
Proinsulin; biologically inactive form of Insulin.
Amylin is found in pancreas of patients of Type 2 Diabetes.

A cells; active when blood glucose level is low, will release = Glucagon.
Glucagon prevents the rapid fall in blood glucose, can release glucose from liver, adipose tissues.

D cells = Somatostatin; Universal Inhibitor; inhibits B cells & A cells.

Blood supply to Islets of Langerhans; directly into center where B cells are. Then through fenestrated capillaries supply rest of the cell. After that blood will move into the venules.
Blood flow pattern is therefore, from center to the periphery. Insulin moves along the pattern with blood; suppressing A cells on the way.

Structure of Precursor of Insulin (PreProinsulin) = Initial segment/Signal sequence, Bchain, Achain & remaining component connects A and B chain = Connecting peptide/Cchain.

When Signal sequence is destroyed; remaining Bchain + Cchain + Achain is actually ProInsulin.
Proinsulin has disulfide bonds; connecting Bchain with Achain.
When Csegment is cut off; Cpeptide is released, only A + B chain remains. This is biologically active Insulin.
Summary of formation of active Insulin from Preproinsulin.

Synthesis of Insulin from genetic level; short arm of chromosome no 11, gene for Insulin.
Transcription; mRNA in cytoplasm, gets attached with ribosomes; which will translate into Amino Acid sequence of a protein; Signal sequence formation.
Signal Sequence is hydrophobic and will take ribosome into Rough Endoplasmic Reticulum (RER); Initial segments will get attached with RER repeatedly in this manner.
Ultimately long Initial Sequence is formed inside the RER and proinsulin formed; released in form of vesicles loaded with Proinsulin molecules.


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