Diabetes-1 (1)

Question 1

What are the two types of diabetes mellitus?

Answer 1

Type-1 diabetes mellitus (T1DM) and Type-2 diabetes mellitus (T2DM)

Question 2

What is the primary characteristic of Type-1 diabetes mellitus?

Answer 2

Autoimmune destruction of insulin-producing beta-cells

Question 3

List some complications linked to diabetes mellitus.

Answer 3

• Cardiomyopathy
• Nephropathy
• Neuropathy
• Retinopathy

Question 4

What is a common diagnostic feature of T1DM?

Answer 4

Presence of insulitis and beta-cell auto-antibodies

Question 5

What primarily causes Type-2 diabetes mellitus?

Answer 5

Dysfunctional insulin receptors and/or pathways involved in insulin signal transduction

Question 6

What percentage of diabetes mellitus cases are Type-2?

Answer 6

About 90%

Question 7

What common pathophysiological feature do T1DM and T2DM share?

Answer 7

Persistent hyperglycemia

Question 8

What is the role of glucose transporters (GLUT) in glucose metabolism?

Answer 8

Facilitate glucose uptake into tissues

Question 9

Which glucose transporter is primarily found in pancreatic beta-cells?

Answer 9

GLUT2

Question 10

What stimulates insulin secretion?

Answer 10

• Elevated blood glucose levels
• Acetylcholine
• Glucagon
• Various hormones like GIP and hCG

Question 11

What inhibits insulin secretion?

Answer 11

• Low glucose concentration
• Fasting
• Exercise
• Somatostatin

Question 12

What is the effect of insulin on blood glucose levels?

Answer 12

Reduces blood glucose (hypoglycemia)

Question 13

What does glucagon do in relation to blood glucose levels?

Answer 13

Promotes conversion of glycogen stores to glucose, increasing blood glucose (hyperglycemia)

Question 14

What is the major regulator of insulin secretion?

Answer 14

Glucose

Question 15

True or False: Oral glucose is a more powerful stimulant for insulin secretion than intravenous glucose.

Answer 15

True

Question 16

What are the factors determining the number of insulin receptors on a target cell?

Answer 16

• Receptor synthesis
• Endocytosis and recycling of receptors
• Endocytosis by degradation

Question 17

What happens to insulin receptors in hyperinsulinemia?

Answer 17

There are fewer receptors due to downregulation

Question 18

What are the three mechanisms by which the insulin receptor transmits signals?

Answer 18

• Binding and phosphorylation by SH2 proteins
• Tyrosine-phosphorylation of cytoplasmic proteins
• Phosphorylation of insulin-receptor substrates (IRS)

Question 19

What is the role of insulin-receptor substrates (IRS) in insulin signaling?

Answer 19

They are important docking proteins in the insulin signal transduction pathway

Question 20

Fill in the blank: Type-1 diabetes mellitus is characterized by _______.

Answer 20

[autoimmune destruction of beta-cells]

Question 21

What are the two main factors affecting insulin secretion?

Answer 21

• Blood glucose levels
• Hormonal signals

Question 22

List the GLUT transporters and their primary locations.

Answer 22

• GLUT1: Red blood cells and endothelial cells
• GLUT2: Renal tubular cells, hepatic cells, pancreatic beta-cells
• GLUT4: Adipose tissue, skeletal muscles, cardiac tissue

Question 23

What is the main consequence of impaired insulin secretion or action?

Answer 23

Hyperglycemia

Question 24

What are the four identified members of the IRS family?

Answer 24

IRS-1, IRS-2, IRS-3, IRS-4

Question 25

What is the primary role of IRS-1?

Answer 25

Major role in skeletal muscle

Question 26

What does IRS-2 regulate?

Answer 26

Hepatic insulin action and pancreatic beta-cell development and survival

Question 27

What roles do IRS-3 and IRS-4 play in the IRS signaling system?

Answer 27

They appear to play a redundant role

Question 28

What defect has been reported in muscle IRS-1?

Answer 28

Defects in insulin-resistant type 2 diabetes

Question 29

What happens when insulin binds to its receptor?

Answer 29

The insulin receptor phosphorylates itself and other cytoplasmic proteins including IRS

Question 30

What does phosphorylated IRS act as?

Answer 30

Docking proteins between the insulin receptor and intracellular signaling molecules

Question 31

Which pathway does PI 3-kinase give rise to?

Answer 31

Phosphatidylinositol-dependent kinase (PDK)

Question 32

What is the effect of PDK in the insulin signaling pathway?

Answer 32

Translocates or inserts GLUT4 into the plasma membrane and enhances glycogen synthesis

Question 33

What does the insulin receptor phosphorylate at tyrosine residues?

Answer 33

SHC

Question 34

What does SHC stimulation lead to?

Answer 34

Activation of transcription factors including Ras, JNK, p38, Raf-1, and MAPK

Question 35

Which kinase is activated by MAPK?

Answer 35

p90-S6 kinase

Question 36

What is the role of p90-S6 kinase?

Answer 36

Phosphorylates a variety of nuclear proteins including protein phosphatase 1 (PP1)

Question 37

What are the treatment strategies for type-1 diabetes mellitus (T1DM)?

Answer 37

Manage with insulin

Question 38

What are the initial management strategies for type-2 diabetes mellitus (T2DM)?

Answer 38

Manage initially with oral hypoglycemic agents, try lifestyle changes

Question 39

What is the target fasting blood glucose level?

Answer 39

4-7 mmol/L

Question 40

What is the target post-prandial blood glucose level (2 hours)?

Answer 40

5-10 mmol/L

Question 41

What is measured for chronic monitoring of glucose?

Answer 41

Hemoglobin A1c (HbA1c)

Question 42

What is the target HbA1c level for diabetic management?

Answer 42

<7%

Question 43

What are the classes of anti-diabetic therapy for diabetic patients?

Answer 43

* Insulin * Insulin secretagogues * Biguanides * Incretins * Thiazolidinediones * Alpha-glucosidase inhibitors * SGLT-2 inhibitors

Question 44

What is the structure of insulin?

Answer 44

A 51 amino acid protein consisting of two peptide chains (A and B) joined by 2 disulphide bridges

Question 45

What is one action of insulin regarding glucose?

Answer 45

Promotes entry of glucose into cells

Question 46

What is the major site of insulin's effects?

Answer 46

* Liver * Muscles * Adipose tissue

Question 47

What does insulin promote in the liver?

Answer 47

* Storage of glucose as glycogen * Lipogenesis * Stimulate protein metabolism

Question 48

What is the pharmacokinetics of insulins regarding administration?

Answer 48

Most commonly injected subcutaneously, intravenous route used in emergencies

Question 49

What affects the absorption of insulin when injected subcutaneously?

Answer 49

* Site of injection * Regional blood flow

Question 50

What is NPH insulin?

Answer 50

Neutral Protamine Hagedorn insulin, a complex with Zinc/Protamine

Question 51

What are the characteristics of rapid-acting insulin?

Answer 51

* Onset: ~1/4 hour * Peak: 1-1.5 hours * Duration: 4 hours

Question 52

What are the side effects of insulin?

Answer 52

* Hypoglycemia * Weight gain * Immune reactions * Lipo-dystrophy

Question 53

What do insulin secretagogues do?

Answer 53

Promote insulin secretion

Question 54

What is the prototype of sulfonylureas?

Answer 54

Glyburide

Question 55

What mechanism do sulfonylureas use to stimulate insulin release?

Answer 55

Bind to the sulfonylurea receptor-1 (SUR-1) and inhibit the K ATP channel

Question 56

What is the prototype of meglitinides?

Answer 56

Repaglinide

Question 57

What is the main mechanism of biguanides?

Answer 57

Increases activity of AMP-dependent protein kinase (AMPK)

Question 58

What are the key effects of AMPK?

Answer 58

* Enhanced glucose uptake/cell sensitivity to insulin * Reduced glycogenolysis * Reduced gluconeogenesis

Question 59

What is a significant side effect of metformin?

Answer 59

* Gastrointestinal issues * Nausea * Diarrhea

Question 60

What are the main characteristics of biguanides?

Answer 60

* Considered first line for T2DM * Not associated with weight gain * Good safety profile