Question 1

What is preproinsulin and how is it structured?

Accepted Answer

Preproinsulin is the initial protein synthesized by the endoplasmic reticulum in pancreatic β-cells. It comprises four components: a signal peptide, the A chain, the B chain, and a C-peptide. The signal peptide is cleaved during processing, and disulfide bonds form between the A and B chains to create proinsulin, which is then transported to the Golgi apparatus for further modification.

Question 2

How does proinsulin become mature insulin?

Accepted Answer

Proinsulin is transported to the Golgi apparatus and packaged into secretory granules. Within these granules, enzymes called prohormone convertases cleave proinsulin, separating the C-peptide from insulin. The mature insulin molecule contains the disulfide-linked A and B chains and is stored in granules until secretion is triggered.

Question 3

What causes diabetes when β-cells are damaged?

Accepted Answer

When pancreatic β-cells are damaged or functionally impaired, they cannot produce sufficient insulin. This suppression of insulin production leads to diabetes, characterized by hyperglycemia—elevated blood glucose levels. The inability to regulate blood glucose results from the loss of insulin's glucose-lowering effects on target tissues.

Question 4

How does insulin lispro differ from regular insulin?

Accepted Answer

Insulin lispro is a rapid-acting analog created by reversing the 28th and 29th amino acids in the B chain of regular insulin. This modification allows insulin lispro to form monomers, enabling rapid absorption into the bloodstream. In contrast, regular insulin forms dimers and hexamers, which delays its absorption and onset of action.

Question 5

What modifications make insulin glargine long-acting?

Accepted Answer

Insulin glargine is a long-acting analog with two key structural modifications: asparagine at position 21 is replaced with glycine, and two arginine residues are added to the B chain. Upon injection, insulin glargine precipitates at physiological pH 7.4, creating a depot that slows absorption and extends its duration of action compared to regular insulin formulations.

Question 6

What are the main insulin formulations used in diabetes treatment?

Accepted Answer

Diabetes therapy primarily uses recombinant human insulin in two standard formulations: regular insulin and neutral protamine hagedorn (NPH). Additionally, rapid-acting and long-acting analogs are available, created through amino acid sequence modifications. These formulations allow clinicians to tailor insulin therapy to individual patient needs and glucose patterns.

Question 7

Why is modifying insulin structure important for diabetes management?

Accepted Answer

Modifying insulin structure through amino acid changes creates analogs with different absorption and action profiles. These modifications enable rapid-acting insulins for mealtime glucose control and long-acting insulins for basal coverage. Tailoring insulin pharmacokinetics to patient needs improves glycemic control and reduces hypoglycemic episodes in diabetes management.

胰岛素：生物合成、化学和制备

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