Insulin Secretion Mechanism Quiz

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Questions and Answers

What is the primary trigger for insulin secretion?

Block of K+ channels

High levels of ATP

Activation of transcription factors

Increased glucose levels (correct)

Which type of insulin is normally catabolized by insulinase produced by the kidney?

Beef insulin

Pork insulin

Human insulin (correct)

Insulin from DNA technology

Why does oral glucose elicit more insulin secretion than IV glucose?

Gut hormone release (correct)

Membrane depolarization

Higher ATP production

Increased Ca2+ influx

What is the structure of human insulin?

51 amino acids connected by 1 disulfide bridge Signup and view all the answers

Which insulin preparation is modified to have prolonged action?

Lantus Signup and view all the answers

What is the main effect of increased ATP levels in β-cells?

Induces an influx of Ca2+ Signup and view all the answers

Why does oral administration of glucose elicit more insulin secretion?

Causes gut hormone release augmenting the insulin response Signup and view all the answers

How does metformin enter the cell?

Through SLC22A1 and inhibiting mitochondrial complex I Signup and view all the answers

What is the result of inhibiting mitochondrial complex I by metformin?

Reduced ATP levels and accumulation of AMP Signup and view all the answers

How do α-Glucosidase inhibitors like acarbose and miglitol delay carbohydrate digestion?

By competitively inhibiting α-glucosidase activity Signup and view all the answers

What is the pharmacokinetics of acarbose used as an α-Glucosidase inhibitor?

Poorly absorbed and remains in the intestinal lumen Signup and view all the answers

Which enzyme hydrolyses oligosaccharides to monosaccharides in the intestine?

Alpha-glucosidase Signup and view all the answers

What is a common adverse effect of α-Glucosidase inhibitors like acarbose and miglitol?

Flatulence, diarrhea, cramping Signup and view all the answers

What is the mechanism of action of metformin on gluconeogenesis?

Suppresses gluconeogenesis by reducing enzyme activity and gene expression Signup and view all the answers

How does the change in energy charge induced by metformin affect AMPK activation?

Activates AMPK due to low ATP levels Signup and view all the answers

What is the primary function of GLP-1 in relation to insulin secretion?

It stimulates insulin secretion Signup and view all the answers

What is the primary purpose of combining short-acting and longer-acting insulin preparations?

To achieve a consistent and sustained lowering of glucose levels Signup and view all the answers

Which of the following statements about regular insulin is true?

It is produced using genetically engineered bacteria Signup and view all the answers

How does GLP-1 affect glucagon secretion?

It suppresses glucagon secretion Signup and view all the answers

What happens to native GLP-1 after parenteral administration?

It is rapidly degraded by dipeptidyl peptidase-IV (DPP-IV) Signup and view all the answers

Compared to regular insulin, ultrashort-acting insulin preparations like lispro, aspart, and glulisine have:

A more rapid onset of action Signup and view all the answers

When should lispro insulin be administered in relation to a meal?

15 minutes before the meal Signup and view all the answers

Which of the following is a mechanism of insulin action?

It binds to specific high-affinity membrane receptors with tyrosine kinase activity Signup and view all the answers

Which of the following statements about glulisine insulin is true?

It can be given up to 20 minutes after starting a meal Signup and view all the answers

What is the effect of insulin on glucose transport in muscle cells?

It increases glucose transport Signup and view all the answers

Which of the following is NOT an action of insulin on adipose tissue?

It increases gluconeogenesis Signup and view all the answers

What is the primary difference between lente insulin and isophane (NPH) insulin?

Lente insulin is combined with protamine, while NPH is not Signup and view all the answers

What is the goal of insulin therapy in diabetic patients?

To mimic the normal basal, prandial, and post-prandial secretion of insulin Signup and view all the answers

Which of the following statements about lente insulin is true?

It is a combination of regular insulin and ultralente insulin Signup and view all the answers

What is the purpose of combining insulin with protamine in the case of isophane (NPH) insulin?

To delay the onset of action and prolong its effectiveness Signup and view all the answers

Which of the following is NOT an action of insulin on the liver?

It increases triglyceride synthesis Signup and view all the answers

Which drug class for treating Type 2 Diabetes stimulates the release of insulin from pancreatic islet cells?

Sulfonylureas Signup and view all the answers

What is the most common adverse effect associated with Sulfonylureas?

Hypoglycemia Signup and view all the answers

How do Sulfonylureas increase the sensitivity of insulin receptors on target cells?

By blocking potassium channels in beta-cell membranes Signup and view all the answers

Which Sulfonylurea has the shortest duration of action?

Tolbutamide Signup and view all the answers

What is the primary mechanism of action of Sulfonylureas on beta-cells?

Blocking ATP-sensitive potassium channels Signup and view all the answers

In what way do Sulfonylureas affect glucagon secretion?

Reduce glucagon secretion Signup and view all the answers

What happens in cases of hepatic or renal insufficiency with Sulfonylureas?

Increased risk of hypoglycemia Signup and view all the answers

How do Sulfonylureas impact insulin receptors in target tissues?

Increase the binding of insulin to target tissues Signup and view all the answers

Study Notes

GLP-1 and Insulin

GLP-1 stimulates insulin secretion, suppresses glucagon secretion, slows gastric emptying, reduces food intake, increases β cell mass, maintains β cell function, improves insulin sensitivity, and enhances glucose disposal.
The glucose-lowering effects of GLP-1 are preserved in type 2 diabetics.
However, native GLP-1 is rapidly degraded by dipeptidyl peptidase-IV (DPP-IV) after parenteral administration.
GLP-1 receptor (GLP-1R) agonists and DPP-IV inhibitors have shown promising results in clinical trials for the treatment of type 2 diabetes.

Mechanism of Insulin Action

Insulin binds to specific high-affinity membrane receptors with tyrosine kinase activity.
Phosphorylation cascade results in the translocation of Glut-4 (and some Glut-1) transport proteins into the plasma membrane.
It induces the transcription of several genes resulting in increased glucose catabolism and inhibits the transcription of genes involved in gluconeogenesis.
Insulin promotes the uptake of K+ into cells.

Action of Insulin on Various Tissues

Liver: ↓ glucose production, ↑ glucose transport, ↑ glycolysis
Muscle: ↑ glucose transport, ↑ glycolysis
Adipose: ↓ glucose production, ↑ glucose transport, ↑ lipogenesis, ↑ lipoprotein lipase activity, ↑ TG synthesis, ↑ glycogen deposition, ↓ intracellular lipolysis, ↑ protein synthesis

Insulin Therapy

The goal of insulin therapy is to mimic the normal basal, prandial, and post-prandial secretion of insulin.
Short-acting forms are usually combined with longer-acting preparations to achieve this effect.
Rapid Onset and Ultrashort-acting Preparations:
- Regular insulin: short-acting, soluble, crystalline zinc insulin, usually given subcutaneously, rapidly lowers glucose levels.
- Lispro, Aspart & Glulisine preparations: classified as ultrashort-acting forms with an onset more rapid than regular insulin and a shorter duration.
Intermediate–acting Insulin Preparations:
- Lente insulin: amorphous precipitate of insulin with zinc ion combined with 70% ultralente insulin, onset is slower but more sustained than regular insulin.
- Isophane NPH insulin: suspension of crystalline zinc insulin combined with protamine (a polypeptide), conjugation with protamine delays its onset of action and prolongs its effectiveness.

Type 2 Diabetes Treatment

Classes of Oral Hypoglycemic Drugs:
- Sulfonylureas
- Biguanides
- Thiazolidinediones
- Alpha-glucosidase inhibitors
- Meglitinides
Sulfonylureas:
- Stimulate release of insulin from pancreatic islet cells
- Increase sensitivity of insulin receptors on target cells
- Most common adverse effect is hypoglycemia
Alpha-Glucosidase Inhibitors:
- Acarbose and miglitol: delay carbohydrate digestion by competitively inhibiting α-glucosidase
- Pharmacokinetics: Acarbose is poorly absorbed, remaining in the intestinal lumen; Miglitol is absorbed and excreted by the kidney
- Adverse Effects: GUESS (flatulence, diarrhea, cramping)

Metformin

Enters the cell through transporters such as SLC22A1
Inhibits mitochondrial complex I, resulting in reduced ATP levels and an accumulation of AMP
Activates AMPK, which suppresses fat metabolism and possibly also contributes to the reduced gluconeogenic gene expression

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Description

Test your knowledge on the mechanism of insulin secretion in response to glucose levels. Learn how elevated glucose levels lead to increased ATP levels in β-cells, resulting in insulin release through a series of cellular events.