Illustrate the mechanism of action of sulfonic urea used as oral hypoglycemic agents. Enumerate the role of insulin on glucose utilization.

MOA of Sulfonyl Acid Derivatives

Sulfonylureas (Tolbutamide, Chlorpropamide), a class of sulfonyl acid derivatives, have a significant action in lowering blood glucose levels in normal subjects and in type 2 diabetics.

The mechanism of action of sulfonylureas involves provoking a brisk release of insulin from the pancreas.

MOA: 

(1) They act on the so-called ‘sulfonylurea receptors’ (SUR1) on the pancreatic β cell membrane. 

(2) This action causes depolarization by reducing the conductance of ATP-sensitive K+ channels. (Raised ATP production followed by raised Glucose also reduces the conductance of ATP sensitive K+ Channels)

(3) This process enhances Ca2+ influx (Followed by the stimulation of Voltage sensitive Ca++ Channel) and degranulation (followed by calcium dependent translocation), which increases the rate of insulin secretion.

Please note that sulfonylureas are only effective when the patient has some residual pancreatic beta cell activity.

They do not cause hypoglycemia in pancreatectomized animals and in type 1 diabetics. 

ROLE of INSULIN in GLUCOSE UTILIZATION

Insulin plays a crucial role in regulating glucose uptake and utilization throughout the body. It acts as a key hormone in maintaining blood glucose homeostasis.

Primary Mechanism of Insulin in Glucose Utilization:

Glucose Absorption: When carbohydrates are consumed, body breaks them down into glucose, a simple sugar that serves as a vital energy source. 

(a) Insulin attaches to insulin receptors of the target cell.
(b) Activates a cascade of signaling leading to the formation of certain protein called GLUT4 which is a glucose transporter protein, 
(c) GLUT4 is then translocated to the Plasma membrane and Transport glucose into the cell.
(d) Inside the cell Glucose converted to Glucose-6-phosphate which is used as a source of energy. 
- In that way the glucose absorption pathway is regulated by the action of Insulin. 



  • Facilitates glucose uptake by cells: above MECHANISM

  • Promotes glycogen synthesis in the liver: Insulin stimulates the enzyme glycogen synthase, which promotes the conversion of glucose into glycogen for storage in the liver. This helps to lower blood glucose levels after a meal.

  • Inhibits glycogenolysis in the liver: Glycogenolysis is the process of breaking down glycogen into glucose. Insulin inhibits this process by activating an enzyme called protein phosphatase I (PP1), which dephosphorylates and inactivates glycogen phosphorylase, the enzyme responsible for glycogen breakdown.

  • Inhibits lipolysis in adipose tissue: Insulin inhibits lipolysis by inhibiting hormone-sensitive lipase (HSL), the enzyme responsible for triglyceride breakdown. This prevents the release of fatty acids into the bloodstream.

 


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