Insulin – Receptors And Regulation Of Secretion

Insulin – Receptors And Regulation Of Secretion


INSULIN – RECEPTORS AND REGULATION OF SECRETION

Insulin:

  • Two-chain polypeptide hormone, with 51 amino acids.
  • Structure: 
  • 2 chains – A & B chain.
  • A – chain – 21 amino acids; B – chain – 30 amino acids.
  • Half-life-: About 5 mins.

Synthesis:

  • Synthesized as larger preprohormone (Pre-proinsulin) entering ER.
  • Removal of 23 amino-acid signal peptide takes place.
  • Converted to “Prohormone -Proinsulin”.

Proinsulin structure:

  • Made up A & B chain, connected by C-peptide/chain.
  • C-peptide – Detached from granules before secretion.
  • 90% – 97% insulin from B cells.
  • Along with equimolar amounts of C-peptide.

RECEPTORS:

  • Combination of four subunits.
  • Held together by disulfide linkages 
  • 2 alpha subunits.
  • 2 Beta subunits.

1. Alpha subunits:

  • Entirely outside cell membrane
  • As “Insulin binding site”.

2. Beta subunits:

  • Penetrate through cell membrane & protrude into cytoplasm.
  • Locally attached to tyrosine kinase.
  • Hence, example of enzyme-linked receptor.
  • Insulin belongs to group IID hormone.

REGULATION:

1. Plasma glucose concentration.

  • Increased plasma glucose concentration stimulate insulin release
Events:
  • Glucose entry “Insulin independent” via GLUT-2 transporters.
  • Metabolized to pyruvate.
  • Enters citric acid cycle in B cells & generates ATP.
  • ATP inhibits ATP-sensitive K+ channels.
  • Reducing K+ effux.
  • Depolarizing B-cell & Ca2+ enters cell via voltage gated Ca2+ channels.
  • Ca2+ influx causes efflux of insulin from secretory granules (Insulin secretion).
  • Readily releasable insulin-containing secretory granules pool produces insulin secretion initial spike.
  • Pyruvate metabolism via citric acid cycle → Increased intercellular glutamate.
  • Glutamate causes insulin release from 2° secretory granules pool.
  • Prolonged insulin release second phase.

FACTORS INFLUENCING INSULIN SECRETION:

1. Stimulating factor:

  • Glucose – Relationship between glucose concentration & insulin secretion is “SIGMOIDAL
  • Mannose
  • Amino acids (arginine, leucine)
  • Intestinal hormones –
  • GIP.
  • Gastrin.
  • Secretin.
  • CCK
  • GLP -1.
  • β-keto acids
  • Parasympathetic stimulation – 
  • Acetylcholine
  • cAMP
  • β-adrenergic stimulation.
  • Drugs:
  • Theophylline.
  • Sulfonylureas.
  • Endocrine hormones like Growth hormone, Glucagon & Glucocorticoids.

2. Inhibiting factors:

  • Somatostatin
  • 2-deoxyglucose
  • Mannoheptulose
  • α-adrenergic stimulation
  • β-adrenergic inhibitors
  • Galanin
  • Alloxan
  • Electrolyte – K+ depletion
  • Drugs:
  • Diazoxide.
  • Thiazide diuretics.
  • Phenytoin.
  • Microtubule inhibitors
  • Note: Insulin itself is an inhibitor 

LATEST RESEARCH POINTS:

GLP-1 (7-36):

  • Glucagon-like polypeptide 1 (7-36).
  • An additional gut factor for insulin secretion.
  • GLP-1 – More potent insulinotropic hormone. 
Exam Question
 

INSULIN – RECEPTORS AND REGULATION OF SECRETION

Insulin:

  • Two-chain polypeptide hormone, with 51 amino acids.
  • Structure:
  • 2 chains – A-chain – 21 amino acids; B-chain – 30 amino acids.
  • Half-life: About 5 mins.

Synthesis:

  • Synthesized as larger preprohormone (Pre-proinsulin)
  • Converted to “Prohormone” (Proinsulin).
  • Proinsulin structure – Made up A & B chain, connected by C-peptide/chain.
  • Normally, 90% – 97% insulin from B cells,
  • Along with equimolar amounts of C-peptide.

RECEPTORS:

  • Combination of four subunits.
  • 2 Beta subunits – 
  • Gets attached locally to tyrosine kinase.
  • Hence, insulin receptor is an example of enzyme-linked receptor.
  • Insulin belongs to group IID hormone.

REGULATION:

1. Plasma glucose concentration:

  • Increased plasma glucose concentration stimulate insulin release. 
  • Glucose entry is “Insulin-independent” via GLUT-2.
  • Glucose metabolized to pyruvate.
  • Ca2+ influx causes insulin efflux from secretory granules (secretion).

FACTORS INFLUENCING:

1. Stimulating factor:

  • Glucose – Relationship between glucose concentration & insulin secretion is “SIGMOIDAL
  • Intestinal hormones –
  • GIP.
  • Gastrin.
  • Secretin.
  • CCK
  • GLP -1.
  • Parasympathetic stimulation – via acetylcholine.
  • Endocrine hormones – Growth hormone, Glucagon & Glucocorticoids.

2. Inhibiting factors:

  • α-adrenergic stimulation.
  • K+ depletion

LATEST RESEARCH POINTS:

  • GLP-1 (7-36):
  • Glucagon-like polypeptide 1 (7-36)
  • GLP-1 – More potent insulinotropic hormone. 
Don’t Forget to Solve all the previous Year Question asked on Insulin – Receptors And Regulation Of Secretion

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