PATHOPHYSIOLOGY & DIAGNOSIS

OVERVIEW

 

Diabetes Mellitus is a chronic disease of carbohydrate metabolism characterized by hyperglycemia.  Hyperglycemia is the result of insufficient insulin production and release, resistant to the action of insulin or a combination of both factors

 

NORMAL PHYSIOLOGY

The adult pancreas is made up of collections of cells called islets of Langerhans. There are four major cell types in the islets of Langerhans. They are –

  • a Cells – produce Glucagon. It increases plasma glucose by stimulating hepatic glycogenolysis and gluconeogenesis ; increases lipolysis in adipose tissue
  • b Cells – produce insulin. Insulin is anabolic à increases the storage of glucose, fatty acids an d amino acids
  • D Cellsproduce somatostatin, which inhibits secretion of insulin, glucagon and pancreatic polypeptide.
  • F (or PP) cellsresponsible for the production of pancreatic polypeptide, which slows absorption of food.

INSULIN RECEPTOR

Insulin receptors are present in almost all cells of the body. It is a glycoprotein tetramer made of 2 α and 2 β subunits linked by disulfide bridges.

MECHANISM OF ACTION OF INSULIN

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EFFECTS OF INSULIN

Reduces rate of release of glucose from the liver by

  • inhibiting glycogenolysis
  • stimulating glycogen synthesis
  • stimulating glucose uptake
  • stimulating glycolysis
  • inhibiting gluconeogenesis

Increases rate of uptake of glucose into all insulin sensitive tissues, notably muscle and adipose    tissue.

EFFECT ON LIPID METABOLISM

  • Reduces rate of release of free fatty acids from adipose tissue.
  • Stimulates de novo synthesis of fatty acids and also conversion of fatty acids to triglycerides in liver.

EFFECT ON PROTEIN METABOLISM…

  • Stimulates transport of free amino acids across the plasma membrane in liver and muscle.
  • Stimulates protein synthesis and reduces release of amino acids from muscle.
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INSULIN

                Insulin is a polypeptide containing 2 chains of amino acids linked by disulfide bridges.

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  • Insulin is synthesized in the rough endoplasmic reticulum of β cells
  • Insulin is synthesized as a part of a larger pre-pro-hormone called preproinsulin
  • Release of connecting peptide or C-peptide
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Rapid (seconds):

Increased transport of glucose, amino acids, and K+ into insulin sensitive cells.

Intermediate (minutes):

  • Stimulation of protein synthesis
  • Inhibition of protein degradation
  • Activation of glycogen synthase and increased glycogenesis
  • Inhibition of phosphorylase and gluconeogenic enzymes (decreased gluconeogenesis)

Delayed actions (hours):

  • Increase in mRNAs for lipogenic and other enzymes (increased lipogenesis)

EFFECT ON CARBOHYDRATE METABOLISM